- Email: [email protected]
DUPLEX SCANNING AND THE TRANSPLANTED KIDNEY
219 We first confirmed a preliminary report’ (based on a statistically insignificant sample size) suggesting that the polymorphism was prevalent in the normal population by screening 32 normal, unrelated individuals (58 X chromosomes) and found the rarer, FIXOPl allele to be present at a frequency of 0-33 (95% confidence limits 0-21-0-45). From this we predict a heterozygote frequency of 45 %. In common with other polymorphisms in the factor IX gene, FIXOP1 is in linkage disequilibrium with the other polymorphic loci,l,3 which limits but does not abolish its use in carrier diagnosis. When used alone, FIXOPl will permit diagnosis of 45% of potential carriers. When used on pedigrees homozygous for the TaqI, XmnI, DdeI, and MspI RFLPs FIXOPI will marginally increase the overall "catch" from 76% to 80%. An example of the application of this polymorphism in carrier diagnosis is shown in the figure. The defective gene carried by obligatory carrier IIs is clearly migrating on the FIXOPI - allele, and daughter III6, having inherited this allele from her mother, is therefore diagnosed as a carrier. The clear results obtained when using this pair of oligonucleotide probes should enable the FIXOP11 polymorphism to be used, together with existing RFLPs, for carrier and antenatal diagnosis in the routine clinical laboratory setting. Sir William Dunn School of Pathology,
University of Oxford, Oxford OX1 3RE
1. Winship PR,
using
two
in having a zero-shift display, an extended range Doppler mode, and variable sample volume, permitting a more precisely resolved peak frequency shift. All the patients were also examined by sequential angiourography with image subtraction or digital angiography, and positive cases were investigated by selective
arteriography. The echo Doppler study gave the following results: no cases of renal vein thrombosis; 20 cases of altered renal artery velocity waveform (peak velocity with high energy and broad-band Doppler spectra), suggestive of stenosis; and 3 cases of intraparenchymal flow characterised by the loss of a normal velocity waveform and by marked were
turbulence, indicative of arteriovenous fistula. No
tests
technically inadequate. Angiography yielded no cases of renal
vein thrombosis; 14 cases of renal artery stenosis (7 with end-to-end anastomosis); and 3 cases of arteriovenous fistula (all had previously undergone a renal biopsy). Duplex scanning proved reliable for the detection of renal artery stenosis (table).
RENAL ARTERY STENOSIS IN TRANSPLANTED KIDNEY: COMPARISON BETWEEN DUPLEX SCAN AND ANGIOGRAPHY
P. R. WINSHIP G. G. BROWNLEE
Anson DS, Rizza CR, Brownlee GG. Carrier detection in haemophilia B further intragenic restriction fragment length polymorphisms. Nucl
Acids Res 1984; 12: 8861-72. 2. Giannelli F, Choo KH, Winship PR, Rizza CR, Anson DS, Rees DJG, Ferrari N, Brownlee GG. Characterisation and use of an intragenic polymorphic marker for detection of carriers of haemophilia B (factor IX deficiency). Lancet 1984; i: 239-41. 3. Camerino G, Oberle I, Drayna D, Mandel J-L. A new MspI restriction fragment Genet 1985; 71: 79-81. length polymorphism in the hemophilia B locus. Hum J 4. Hay CW, Robertson KA, Yong SN, Thompson AR, Growe GH, MacGillivray RCA. Use of a BamHI polymorphism in the factor IX gene for the determination of hemophilia B carrier status.Blood 1986; 67: 1508-11. 5. Brownlee GG. The molecular genetics of haemophilia A and B. J Cell Sci 1986 suppl 4; 445-58. 6. Weatherall DJ. The new genetics and clinical practice, 2nd ed. Oxford: Oxford University Press, 1985. 7. McGraw RA, Davis LM, Noyes CM, Graham JB, Roberts HR, Stafford DW. Evidence for a prevalent dimorphism in the activation peptide of human coagulation factor IX. Proc Natl Acad Sci USA 1985; 82: 2847-51. 8. Yoshitake S, Schack BG, Foster DC, Davie EW, Kurachi K. Nucleotide sequence of the gene for human factor IX (antihaemophilic factor B). Biochemistry 1985; 24: 3736. 9. Anson DS, Choo KH, Rees DJG, Giannelli F, Gould K, Huddleston JA, Brownlee GG. The gene structure of human anti-haemophilic factor IX. EMBO J 1984; 3: 1053-60. 10. Conner BJ, Reyes AA, Morin C, Ikatura K, Teplitz RL, Wallace RB. Detection of sickle cell &bgr;s-globin allele by hybridisation with synthetic oligonucleotides. Proc Natl Acad Sci USA 1983; 80: 278-82.
DUPLEX SCANNING AND THE TRANSPLANTED KIDNEY to your April 5 editorial on duplex scans to flow in the renal artery of transplanted kidney, we would like to report our own experience. Greene, Avasthi, and colleagues1,2 have described the method as applied to the study of renal artery flow and to the diagnosis of renal artery stenosis. The heterotopic site of the grafted kidney makes the study of arterial flow much easier. We have examined 45 male and 21 female patients aged 16-62 (average 39 years) who had had a cadaver renal graft 4-25 (average 12) months earlier. The anastomosis of the renal artery was end-to-side with the iliac artery in 42 cases and end-to-end with the hypogastric artery in 21. We used an ATL duplex scanner (MK 500 in 30 patients, MK 600 in the rest). Once the vessel image has been obtained, the Doppler beam axis is displayed and can be moved to any site within the imaged sector. The volume in which the velocities are to be measured (sample volume) can be placed in any position along the Doppler beam. A fast Fourier transform analyser is used to plot the spectra of audiofrequencies generated by the blood velocities within the imaged vessels. The MK 600 scanner differs from the MK 500
SIR,-In response
study blood
These findings suggest, bearing in mind the fragility of the transplanted kidney, that a duplex scan should be the first-choice test for vascular monitoring of a renal graft and for selecting patients for angiography, an invasive procedure with potential risks. Ultrasound Diagnostic Unit, General Medicine Department, Ospedale S.G.B. Cottolengo, 10152 Turin, Italy
G. FERRETTI A. SALOMONE
Institute of Nephrology, University of Turin, and Nephrology and Dialysis Department, Ospedale S.G. Battista, Turin
B. MALFI G. P. SEGOLONI
1. Greene ER, Venters MD, Avasthi PS, Conn RL, Jahnke RW. Noninvasive characterization of renal artery blood flow. Kidney Int 1981; 20: 523-29. 2. Avasthi PS, Voyles WF, Greene ER. Noninvasive diagnosis of renal artery stenosis by echo-doppler velocimetry. Kidney Int 1984; 25: 824-29.
HOMOLOGY BETWEEN THYROGLOBULIN AND ACETYLCHOLINESTERASE: AN EXPLANATION FOR PATHOGENESIS OF GRAVES’ OPHTHALMOPATHY?
SIR,—The pathogenesis of Graves’ ophthalmopathy remains an enigma, although there is good evidence for autoimmune mechanisms. A central problem is the failure to identify the autoantigens against which putative humoral and cell-mediated immunity are directed. A prime candidate has been thyroglobulin (Tg).1,2 However, the localisation of Tg in the retro-ocular tissue has not been explained. A solution may lie in the demonstration by Schumacher et al3 of a significant homology between acetylcholinesterase and the C-terminal portion of thyroglobulin.4 We have analysed this homology in detail and found that it contains 28 3% identical aminoacids and involves the 550 carboxy-tenninal residues of Tg and the entire acetylcholinesterase sequence. Thus both proteins share a common ancestor. Comparison of hydropathy profiless also demonstrates a striking similarity, which is strong evidence that the proteins may have common antigenic determinants.
This structural homology provides an attractive hypothesis for the pathogenesis of Graves’ ophthalmopathy. If autoantibodies
University of Oxford, Oxford OX1 3RE
1. Winship PR,
using
two
in having a zero-shift display, an extended range Doppler mode, and variable sample volume, permitting a more precisely resolved peak frequency shift. All the patients were also examined by sequential angiourography with image subtraction or digital angiography, and positive cases were investigated by selective
arteriography. The echo Doppler study gave the following results: no cases of renal vein thrombosis; 20 cases of altered renal artery velocity waveform (peak velocity with high energy and broad-band Doppler spectra), suggestive of stenosis; and 3 cases of intraparenchymal flow characterised by the loss of a normal velocity waveform and by marked were
turbulence, indicative of arteriovenous fistula. No
tests
technically inadequate. Angiography yielded no cases of renal
vein thrombosis; 14 cases of renal artery stenosis (7 with end-to-end anastomosis); and 3 cases of arteriovenous fistula (all had previously undergone a renal biopsy). Duplex scanning proved reliable for the detection of renal artery stenosis (table).
RENAL ARTERY STENOSIS IN TRANSPLANTED KIDNEY: COMPARISON BETWEEN DUPLEX SCAN AND ANGIOGRAPHY
P. R. WINSHIP G. G. BROWNLEE
Anson DS, Rizza CR, Brownlee GG. Carrier detection in haemophilia B further intragenic restriction fragment length polymorphisms. Nucl
Acids Res 1984; 12: 8861-72. 2. Giannelli F, Choo KH, Winship PR, Rizza CR, Anson DS, Rees DJG, Ferrari N, Brownlee GG. Characterisation and use of an intragenic polymorphic marker for detection of carriers of haemophilia B (factor IX deficiency). Lancet 1984; i: 239-41. 3. Camerino G, Oberle I, Drayna D, Mandel J-L. A new MspI restriction fragment Genet 1985; 71: 79-81. length polymorphism in the hemophilia B locus. Hum J 4. Hay CW, Robertson KA, Yong SN, Thompson AR, Growe GH, MacGillivray RCA. Use of a BamHI polymorphism in the factor IX gene for the determination of hemophilia B carrier status.Blood 1986; 67: 1508-11. 5. Brownlee GG. The molecular genetics of haemophilia A and B. J Cell Sci 1986 suppl 4; 445-58. 6. Weatherall DJ. The new genetics and clinical practice, 2nd ed. Oxford: Oxford University Press, 1985. 7. McGraw RA, Davis LM, Noyes CM, Graham JB, Roberts HR, Stafford DW. Evidence for a prevalent dimorphism in the activation peptide of human coagulation factor IX. Proc Natl Acad Sci USA 1985; 82: 2847-51. 8. Yoshitake S, Schack BG, Foster DC, Davie EW, Kurachi K. Nucleotide sequence of the gene for human factor IX (antihaemophilic factor B). Biochemistry 1985; 24: 3736. 9. Anson DS, Choo KH, Rees DJG, Giannelli F, Gould K, Huddleston JA, Brownlee GG. The gene structure of human anti-haemophilic factor IX. EMBO J 1984; 3: 1053-60. 10. Conner BJ, Reyes AA, Morin C, Ikatura K, Teplitz RL, Wallace RB. Detection of sickle cell &bgr;s-globin allele by hybridisation with synthetic oligonucleotides. Proc Natl Acad Sci USA 1983; 80: 278-82.
DUPLEX SCANNING AND THE TRANSPLANTED KIDNEY to your April 5 editorial on duplex scans to flow in the renal artery of transplanted kidney, we would like to report our own experience. Greene, Avasthi, and colleagues1,2 have described the method as applied to the study of renal artery flow and to the diagnosis of renal artery stenosis. The heterotopic site of the grafted kidney makes the study of arterial flow much easier. We have examined 45 male and 21 female patients aged 16-62 (average 39 years) who had had a cadaver renal graft 4-25 (average 12) months earlier. The anastomosis of the renal artery was end-to-side with the iliac artery in 42 cases and end-to-end with the hypogastric artery in 21. We used an ATL duplex scanner (MK 500 in 30 patients, MK 600 in the rest). Once the vessel image has been obtained, the Doppler beam axis is displayed and can be moved to any site within the imaged sector. The volume in which the velocities are to be measured (sample volume) can be placed in any position along the Doppler beam. A fast Fourier transform analyser is used to plot the spectra of audiofrequencies generated by the blood velocities within the imaged vessels. The MK 600 scanner differs from the MK 500
SIR,-In response
study blood
These findings suggest, bearing in mind the fragility of the transplanted kidney, that a duplex scan should be the first-choice test for vascular monitoring of a renal graft and for selecting patients for angiography, an invasive procedure with potential risks. Ultrasound Diagnostic Unit, General Medicine Department, Ospedale S.G.B. Cottolengo, 10152 Turin, Italy
G. FERRETTI A. SALOMONE
Institute of Nephrology, University of Turin, and Nephrology and Dialysis Department, Ospedale S.G. Battista, Turin
B. MALFI G. P. SEGOLONI
1. Greene ER, Venters MD, Avasthi PS, Conn RL, Jahnke RW. Noninvasive characterization of renal artery blood flow. Kidney Int 1981; 20: 523-29. 2. Avasthi PS, Voyles WF, Greene ER. Noninvasive diagnosis of renal artery stenosis by echo-doppler velocimetry. Kidney Int 1984; 25: 824-29.
HOMOLOGY BETWEEN THYROGLOBULIN AND ACETYLCHOLINESTERASE: AN EXPLANATION FOR PATHOGENESIS OF GRAVES’ OPHTHALMOPATHY?
SIR,—The pathogenesis of Graves’ ophthalmopathy remains an enigma, although there is good evidence for autoimmune mechanisms. A central problem is the failure to identify the autoantigens against which putative humoral and cell-mediated immunity are directed. A prime candidate has been thyroglobulin (Tg).1,2 However, the localisation of Tg in the retro-ocular tissue has not been explained. A solution may lie in the demonstration by Schumacher et al3 of a significant homology between acetylcholinesterase and the C-terminal portion of thyroglobulin.4 We have analysed this homology in detail and found that it contains 28 3% identical aminoacids and involves the 550 carboxy-tenninal residues of Tg and the entire acetylcholinesterase sequence. Thus both proteins share a common ancestor. Comparison of hydropathy profiless also demonstrates a striking similarity, which is strong evidence that the proteins may have common antigenic determinants.
This structural homology provides an attractive hypothesis for the pathogenesis of Graves’ ophthalmopathy. If autoantibodies