The Australian brushtail possum (Trichosurus vulpecula) gonadotrophin alpha-subunit: analysis of cDNA sequence and pattern of expression

Substantial evidence has accumulated to suggest that in the near future implementation of the veto-cell-suppressor concept in the treatment of kidney allograft recipients might lead to the establishment of life-long specific allograft tolerance in the absence of further immunosuppressive therapy. Veto suppression prevents the generation of antigen-specific T-helper and cytotoxic T lymphocytes in vitro provided that the T-lymphocyte precursors specifically recognize antigenic peptides associated with the major histocompatibility complex molecules class II and class I, respectively, expressed on the surface of the veto-active cell. Data from a large number of experimental and clinical studies strongly indicate that veto-active cells function in vivo and are capable of preventing allograft rejection. Thus, donor-cell-mediated veto activity is the most likely explanation for the well-known graft tolerizing effect of pretransplant donor blood transfusions in kidney graft recipients. A prerequisite for a veto-active environment in vivo is the establishment of lymphoid microchimerism, in which veto-active donor and recipient cells mutually downregulate potential alloaggression.     

The syndrome of thrombosis, thrombocytopenia, and recurrent spontaneous abortions associated with antiphospholipid antibodies: Hughes syndrome

aPL-associated thrombosis (Hughes syndrome) is widely recognized as a major cause of organ damage in autoimmune diseases. Beginning with the first symposium in 1984, international aPL symposia have facilitated research on aPL antibodies, and the clinical standardization of aPL tests. It is hoped that the present symposium will continue this tradition, because much remains to be learnt about the origin and pathogenicity of aPL antibodies. In addition, new insights are needed for more effective therapies to be developed.     

Interactions among iron, calcium, phosphorus and magnesium in the nutritionally iron-deficient rat

We studied the development of nutritional iron deficiency 0, 10, 20, 30 and 40 days after the intake of a semisynthetic diet lacking iron (diet 0) and the possible interactions with calcium, phosphorus and magnesium in both control rats and rats after 40 days of iron deficiency. During this period, iron deficiency was found to produce stress in the rats, as evidenced by high levels of cortisol in the serum. High levels of parathyroid hormone (PTH) were also found. There was a considerable increase in the absorption of calcium, phosphorus and magnesium, but the phosphorus and magnesium balance decreased and that of calcium remained practically unchanged, although there was an increase in calcium urinary elimination. Despite the noticeable degree of bone demineralization, which was evident in the femur, serum levels of calcium, phosphorus and magnesium remained constant. The present study shows that severe nutritional ferropenic anaemia provokes significant alterations in the metabolism of calcium, phosphorus and magnesium. We conclude that these alterations should be taken into account in the treatment of this pathology, given its prevalence and the fact that it may exacerbate other pathologies, particularly those related to the metabolism of calcium and phosphorus.     

Mechanism-based inactivation of human liver cytochrome P450 2A6 by 8-methoxypsoralen

The P450 2A6 catalyzed 7-hydroxylation of coumarin proceeded with a mean Km of 0.40 (+/-0.13) microM and Vmax of 6.34 nmol/nmol P450/min (36-fold variation) in microsomal preparations from a panel of 12 human livers. Substrate depletion was avoided during the kinetic determinations. 8-Methoxypsoralen (8-MOP) is a potent mechanism-based inactivator of human liver P450 2A6 and reconstituted purified recombinant P450 2A6 based on the following evidence: 1) 8-MOP causes time, concentration, and NADPH-dependent loss of P450 2A6 activity that is not reversed by potassium ferricyanide or extensive dialysis, 2) loss of P450 2A6 activity is associated with a loss of spectrally observable P450, 3) addition of nucleophiles or reactive oxygen scavengers to the incubations does not prevent inactivation of P450 2A6, and 4) 8-MOP-dependent P450 2A6 inactivation is inhibited (concentration dependent) by the addition of a competitive inhibitor (pilocarpine). Inactivation is selective for P450 2A6 at low concentrations of 8-MOP (2.5 microM) after short incubation time periods (3 min) and was characterized by a KI of 0.8 and 1.9 microM in a reconstituted and microsomal system, respectively, and a kinact of 1 min-1 and 2 min-1 in a reconstituted and microsomal system, respectively. A substrate depletion partition ratio of 21 was calculated for the inactivation of recombinant P450 2A6. Potency and selectivity suggest that 8-MOP could be a useful tool in vitro for evaluating P450 2A6 activity in various enzyme preparations.     

The min K channel underlies the cardiac potassium current IKs and mediates species-specific responses to protein kinase C

A clone encoding the guinea pig (gp) min K potassium channel was isolated and expressed in Xenopus oocytes. The currents, gpIsK, exhibit many of the electrophysiological and pharmacological properties characteristic of gpIKs, the slow component of the delayed rectifier potassium conductance in guinea pig cardiac myocytes. Depolarizing commands evoke outward potassium currents that activate slowly, with time constants on the order of seconds. The currents are blocked by the class III antiarrhythmic compound clofilium but not by the sotalol derivative E4031 or low concentrations of lanthanum. Like IKs in guinea pig myocytes, gpIsK is modulated by stimulation of protein kinase A and protein kinase C (PKC). In contrast to rat and mouse IsK, which are decreased upon stimulation of PKC, myocyte IK and gpIsK in oocytes are increased after PKC stimulation. Substitution of an asparagine residue at position 102 by serine (N102S), the residue found in the analogous position of the mouse and rat min K proteins, results in decreased gpIsK in response to PKC stimulation. These results support the hypothesis that the min K protein underlies the slow component of the delayed rectifier potassium current in ventricular myocytes and account for the species-specific responses to stimulation of PKC.     

Segregation distortion in myotonic dystrophy

Myotonic dystrophy (DM) is an autosomal dominant disease which, in the typical pedigree, shows a three generation anticipation cascade. This results in infertility and congenital myotonic dystrophy (CDM) with the disappearance of DM in that pedigree. The concept of segregation distortion, where there is preferential transmission of the larger allele at the DM locus, has been put forward to explain partially the maintenance of DM in the population. In a survey of DM in Northern Ireland, 59 pedigrees were ascertained. Sibships where the status of all the members had been identified were examined to determine the transmission of the DM expansion from affected parents to their offspring. Where the transmitting parent was male, 58.3% of the offspring were affected, and in the case of a female transmitting parent, 68.7% were affected. Studies on meiotic drive in DM have shown increased transmission of the larger allele at the DM locus in non-DM heterozygotes for CTGn. This study provides further evidence that the DM expansion tends to be transmitted preferentially.     

Persistent acute renal failure with renal artery stenosis: cure following reconstructive arterial operation

A case of acute renal failure is reported in which renal function returned after surgical correction of renal artery stenosis to the sole functioning kidney. Acute renal failure associated with renal vascular lesions is reviewed. Although often clinically apparent vascular obstruction may be asymptomatic and should be considered in cases of prolonged acute renal failure.