Splenectomy and renal allograft survival in the rat

The effect of splenectomy on renal allograft survival is not clear. In the rat, spleens isolated from recipients with functioning grafts have been shown to be a major source of cells that are capable of suppressing the rejection response (suppressor T lymphocytes). Thus the removal of the spleen in these allograft recipients could be detrimental to renal allograft survival. This study investigates this hypothesis, and looks for the presence of suppressor cells in other lymphoid organs apart from the spleen. In the rat renal allograft model, donor Lewis spleen cells given to DA recipients intravenously 1 week before transplantation of a Lewis kidney leads to indefinite allograft survival (median survival time (MST) greater than 100 days). Splenectomy before or after pretreatment with donor spleen cells failed to abrogate this effect (MST greater than 100 days). Experiments were performed in which cells or serum were prepared from long-term surviving splenectomized animals which had already been pretreated and transplanted, and then were injected into untreated recipients (adoptive transfer experiments). This was done to determine if cells capable of suppressing graft rejection were present in lymphoid organs outside the spleen in these splenectomized recipients. Thus the IV transfer of 10(8) lymph node cells harvested from splenectomized DA recipients with a long-term surviving LEW graft (LTS), into untreated but lightly irradiated (200 rad) DA recipients resulted in indefinite survival of a fresh Lewis kidney (MST greater than 100 days). In contrast, adoptive transfer of normal DA lymph node cells was ineffective (MST 13 days). Thus splenectomy is not necessarily detrimental to graft survival, as cells capable of preventing graft rejection are found in other lymphoid organs, such as lymph nodes, in splenectomized recipients.     

Metabolism of the anti-psoriatic agent 5-methoxypsoralen in humans: comparison with rat and dog.

1. Single oral doses of 14C-5-methoxypsoralen (5-MOP) to human subjects (50 mg), rats (1 mg/kg) and dogs (1 mg/kg) were fairly well absorbed but subjected to extensive first-pass metabolism, at least in rat and human. Means of 62, 51 and 40% dose in urine and 31, 38 and 48% dose in faeces, were excreted by humans (during 5 days), rats (3 days) and dogs (1 day), respectively. In dogs, faecal 14C was probably derived, in part, from biliary excreted material. 2. Total 14C in human plasma reached peak concentrations after 2 h (mean 235 ng 5-MOP equivalent/ml) and declined relatively slowly, to about 60% of this value within 24 h. Unchanged 5-MOP was not detected in plasma using h.p.l.c. (< 5 ng/ml). 3. Tissue concentrations of 14C were generally greater in dogs than rats and reached peak levels at 1 h in dogs but at 24 h in rats. Apart from liver and bile, dog tissue 14C concentrations were lower than those in the corresponding plasma, whereas in rat they were lower only until the time of peak concentrations, after which they were generally greater. 4. 5-MOP was extensively metabolized in all three species. The major 14C-components in human and dog urine were glucuronic acid conjugates, mainly of an arylacetic acid and arylalcohols, resulting from initial oxidative metabolism of the furan ring of 5-MOP. In rat, these metabolites were excreted mainly unconjugated. An unusual metabolite was formed by reduction of the lactone moiety of 5-MOP, probably by the gut flora, giving rise to an arylpropionic acid, excreted as a glucuronic acid conjugate in the urine of all three species. 5. Unchanged drug was a very minor component of human and rat plasma, but a major component of dog plasma. In all three species, circulating 14C-metabolites were similar to those in the urine but were present mainly unconjugated. On the basis of these data, the metabolic fate of 5-MOP in humans was more similar to that in dog than to that in rat, although humans appeared to metabolize 5-MOP more rapidly than did dog.     

The response of spontaneous and transplantable murine tumors to vasoactive agents measured by 31P magnetic resonance spectroscopy.

31P magnetic resonance spectroscopy has been used to compare the effects of the vasoactive agents hydralazine and flunarizine on the oxygenation of the transplantable tumors, SCCVII/Ha and 16C, and a range of spontaneous mammary tumors arising in the breeding stock in the Genetics Division at the Radiobiology Unit. The vasodilator hydralazine, previously shown to increase the radiobiological hypoxic fraction of transplantable murine tumors, increased inorganic phosphate to total phosphate (Pi/total) in SCCVII/Ha and 16C tumors. However, only two spontaneous tumors responded to this agent (2/12). The calcium antagonist flunarizine, which sensitizes the SCCVII tumor to X rays, consistent with a reduction in hypoxic fraction, reduced Pi/total in this and the 16C tumor. Further, most spontaneous tumors tested (8/10) responded to this agent, as measured by a reduction in Pi/total. These results point to fundamental differences between transplantable and spontaneously arising tumors in mice in their response to vasoactive agents.     

Gd DTPA. Future applications with advanced imaging techniques

In this admittedly preliminary view of the future, the authors present a number of new concepts in MR imaging and consider their possible advantages and limitations.     

DQ Wa gives rise to a DQβ restriction fragment pattern indistinguishable from that of the DQw3.2 sub-type Of DQw3

DQ beta restriction fragment patterns have been obtained from five DRw8 cell lines homozygous for the null DQ allele, DQWa. The enzymes Bgl II, Bam HI and Pvu II generate DQ beta patterns which are indistinguishable from those obtained from cell lines homozygous for DQw3.2.     

Distribution of retroperitoneal metastases after chemotherapy in patients with nonseminomatous germ cell tumors.

For patients with advanced nonseminomatous germ cell tumors a retroperitoneal lymph node dissection is routinely performed following chemotherapy if the serum tumor markers have returned to normal. Bilateral retroperitoneal lymph node dissection has been recommended because metastatic deposits may be widespread. The aim of this study was to describe the distribution of retroperitoneal metastases following chemotherapy in patients with nonseminomatous germ cell tumor and determine if the extent of the retroperitoneal lymph node dissection can be modified. We studied 113 patients who had initially bulky retroperitoneal disease and underwent retroperitoneal lymph node dissection following chemotherapy. For the purposes of this study teratoma and malignant germ cell tumor are referred to as tumor. The most common location of tumor was the para-aortic area (91%) in patients with a left primary tumor and the interaortocaval area (78%) in those with a right tumor. Tumor was located outside the boundaries of a modified retroperitoneal lymph node dissection in 14 of the 60 patients with residual disease but the tumor was present within a palpable mass in 6 of these 14 patients. If the residual mass was removed and a modified retroperitoneal lymph node dissection was performed only 9 of the 113 patients (8%) would have tumor left in the retroperitoneum. For a select group of patients with advanced nonseminomatous germ cell tumor treated with chemotherapy, resection of the residual mass combined with modified retroperitoneal lymph node dissection is appropriate.     

Types of anterior cervical grafts.

Anterior cervical diskectomy and fusion provide satisfactory results in most instances of cervical disk herniation and cervical spondylosis. A variety of interpositioned grafts have been described for such problems at one or two levels. Multiple level anterior decompression and fusion for patients with spondylotic myelopathy produce satisfactory results in most instances and are particularly effective when a degenerative kyphosis is present. Appropriate patient selection and attention to technical aspects of exposure, neural decompression, and graft procurement and placement directly influence the surgical outcome.     

Invited review: Neuroprotective properties of certain beta-adrenoceptor antagonists used for the treatment of glaucoma.

Although it is known that ganglion cell death causes loss of vision in glaucoma, the pathogenesis of the disease is complex, probably involving an initial ischemic insult to the ganglion cell axons and glial cells with the ganglion cell bodies eventually being affected. It may therefore be necessary to blunt many stages in the pathogenesis of the disease to obtain a clinically effective neuroprotective strategy. In animal experiments, one cause of ganglion cell death in ischemia is an overactivation of glutamate receptors and a subsequent rise in intracellular levels of sodium and calcium ions as well as a generation of reactive oxygen species. In contrast, optic nerve death in ischemia is mainly caused by an influx of sodium and reversal of the sodium/calcium exchanger, which leads to a rise in intracellular calcium. Thus, a substance that reduces the influx of sodium will protect the ganglion cell axon, and if it also reduces calcium influx and/or acts as an antioxidant it will protect the ganglion cell body in addition. Of all antiglaucoma drugs, only beta-blockers have both calcium and sodium channel blocking activity, with betaxolol being the most efficacious of those analyzed. In addition, of the tested ophthalmic beta-blockers only metipranolol has powerful antioxidant properties. Moreover, laboratory studies on rats have shown that topically applied beta-blockers attenuate ischemic injury to ganglion cells by mechanisms that do not appear to involve an action on beta-receptors. Thus, of the substances used to lower intraocular pressure in glaucoma, beta-blockers have unique additional characteristics that also give them the capacity to act as neuroprotectants.