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Autosomal dominant polycystic kidney disease
Notes patients or in the corresponding mouse model, the mdx mouse, die off prematurely in muscle, but no disease symptoms *v’ereobserved in isolated or cu?tured muscle cells: mutant cells survived just as happily as their normal, dystrophin containing counterparts. Therefore, A Menke and H Jockusch of the Developmental Biology Unit of the University of Bielefeld subjected muscle cells from normal and dystrophic mice to hypo-osmotic shock, in which a rather dilute external medium leads to a pressure from inside the fibres and hence to membrane stress and, finally, to lethal membrane rupture. By quantifying the survival after such treatment, it was found that dystrophin-less cells were indeed more susceptible than healthy controls, thus providing an experimental explanation for the lowered survival chance of dystrophic muscle fibres in muscle under working conditions (Menke A, Jockusch H, 1991, Nature (Lund) 349. 69-7 I). AMe~e(l) University of Bielefeld, D 4800 Bielefeld I, Cennuny
Autosomal dominant polycystic kidney disease Autosomal dominant polycystic kidney disease (ADPKD) is responsible for about 10% of end stage renal disease (ESRD); about i/l 000 persons carry a mutation for the disorder. Most ADPKD is due to mutations at the PKDl locus on chromosome 16; in 4% of families ADPKD is due to a mu~tio~ (or mutations) elsewhere. We explored the utility of ultrasonography in the presymptomatic diagnosis of ADPKD. and the prognosis for persons diagnosed presymptomatically. Comparison of ul~asonographic diagnoses with PKDI genotypes determined by linkage analysis of families indicated that false negative ultrasonographic findings are unlikely after the age of 30 years. Mean age of onset of ESRD is 57 years, a better prognosis than is generally absumed. The small proportion of families in which ADPKD is due to mutations elsewhere in the genome contributes little to the probability of a false negative diagnosis; moreover, in such families mean age of onset appears to be later (69 years) than in families with PKDI mutations.
(I) Nature (Land) (I 99 I) 349, 69
425
In principle. genetic linkage analysis of families allows the PKDl genotypes of family members to be inferred with near certainty, but the information necessary for this is often unavailable. The utility of ultrasonography is therefore of obvious interest to persons at risk. If interventions to slow or halt renal deterioration (such as control of accompanying hypertension or restriction of dietary protein intake) are shown to be effective, the clinical importance of presymptomatic identification of individuals with a PKDl mutation will increase. JC Bear (2) Memorial University of
Newfoundland.St John’s MF, Al B3V6, Canada T celk tolerant to S nureus enterotoxin B The mechanisms that underlie tolerance to self and nonself (foreign) antigens are one of the major remaining problems to be solved in immunology. In order to develop a knowledge of T lymphocyte tolerance, we established an experimental system which induces the in viva tolerance to Stup~yl~coec~s aureus enterotoxin B (SEB) in the periphera1 lymphoid system. SEB stimulates T cells whose T cell receptor p chain V regions are encoded by VP7 and 8 genes in the mice system. In viva priming with SEB induced the tolerance of reactive T cells which are represented by V@3+ T cells in spleen and lymph nodes. In the mice tolerant to SEB. we have demonstrated that the number of Vp8+, CD4’ T cells is markedly reduced in the periphery. The expansion of such cells preceded this reduction and was accompanied by genomic DNA fragmentation that is associated with cell death. The remaining V@+, CD4’ cells were unres~nsive to SEB and other T cell mitogens. These results indicate that a deletional mechanism as well as unresponsiveness can contribute to the induction of T cell tolerance in peripheral lymphoid cells. The results were identical when these experiments were carried out in thymectomized mice. Thus the data indicate that extrathymic tolerance can be achieved by both functional inactivation and deletion of antigen-reactive T cells. A Ochi (3) Mounl Sinai Hospital, Toronto,OntarioM5G :X5, Canada
(2) N Engt J Med (1990) 323, IOSS (3) Nurure (Lund) (1991) 349. 245
Autosomal dominant polycystic kidney disease Autosomal dominant polycystic kidney disease (ADPKD) is responsible for about 10% of end stage renal disease (ESRD); about i/l 000 persons carry a mutation for the disorder. Most ADPKD is due to mutations at the PKDl locus on chromosome 16; in 4% of families ADPKD is due to a mu~tio~ (or mutations) elsewhere. We explored the utility of ultrasonography in the presymptomatic diagnosis of ADPKD. and the prognosis for persons diagnosed presymptomatically. Comparison of ul~asonographic diagnoses with PKDI genotypes determined by linkage analysis of families indicated that false negative ultrasonographic findings are unlikely after the age of 30 years. Mean age of onset of ESRD is 57 years, a better prognosis than is generally absumed. The small proportion of families in which ADPKD is due to mutations elsewhere in the genome contributes little to the probability of a false negative diagnosis; moreover, in such families mean age of onset appears to be later (69 years) than in families with PKDI mutations.
(I) Nature (Land) (I 99 I) 349, 69
425
In principle. genetic linkage analysis of families allows the PKDl genotypes of family members to be inferred with near certainty, but the information necessary for this is often unavailable. The utility of ultrasonography is therefore of obvious interest to persons at risk. If interventions to slow or halt renal deterioration (such as control of accompanying hypertension or restriction of dietary protein intake) are shown to be effective, the clinical importance of presymptomatic identification of individuals with a PKDl mutation will increase. JC Bear (2) Memorial University of
Newfoundland.St John’s MF, Al B3V6, Canada T celk tolerant to S nureus enterotoxin B The mechanisms that underlie tolerance to self and nonself (foreign) antigens are one of the major remaining problems to be solved in immunology. In order to develop a knowledge of T lymphocyte tolerance, we established an experimental system which induces the in viva tolerance to Stup~yl~coec~s aureus enterotoxin B (SEB) in the periphera1 lymphoid system. SEB stimulates T cells whose T cell receptor p chain V regions are encoded by VP7 and 8 genes in the mice system. In viva priming with SEB induced the tolerance of reactive T cells which are represented by V@3+ T cells in spleen and lymph nodes. In the mice tolerant to SEB. we have demonstrated that the number of Vp8+, CD4’ T cells is markedly reduced in the periphery. The expansion of such cells preceded this reduction and was accompanied by genomic DNA fragmentation that is associated with cell death. The remaining V@+, CD4’ cells were unres~nsive to SEB and other T cell mitogens. These results indicate that a deletional mechanism as well as unresponsiveness can contribute to the induction of T cell tolerance in peripheral lymphoid cells. The results were identical when these experiments were carried out in thymectomized mice. Thus the data indicate that extrathymic tolerance can be achieved by both functional inactivation and deletion of antigen-reactive T cells. A Ochi (3) Mounl Sinai Hospital, Toronto,OntarioM5G :X5, Canada
(2) N Engt J Med (1990) 323, IOSS (3) Nurure (Lund) (1991) 349. 245