DR2 haplotypes (DRB1, DQA1, DQB1) associated with systemic lupus erythematosus.
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Gene Frequency↗
Biomedical subjects
E Keller
Publications and source records attributed to E Keller.
HLA-DP/DR interaction in early onset pauciarticular juvenile chronic arthritis.
We investigated the polymorphic second exon of the HLA-DPB1 and HLA-DRB1 genes, using in vitro DNA amplification by polymerase chain reaction (PCR) and oligonucleotide hybridization in 136 patients with early onset pauciarticular juvenile chronic arthritis (EOPA-JCA) and 199 healthy controls. The analysis of the HLA-DRB1 system revealed that most of the DRB1 alleles are not indifferent with respect to susceptibility to EOPA-JCA. There is a hierarchy of susceptible (DRB1*08, DR5), "permissive" (DRB1*01), moderately "protective" (DR2, DRB1*04), and "protective" (DRB1*07) alleles. In contrast, no hierarchy could be shown for the HLA-DPB1 system. DPB1*0201 was found to be susceptible. The relatively frequent alleles DPB1*0402 and DPB1*0401 seem to be indifferent. The associations with DPB1*0201, DR5, and DRB1*08 are independent of each other: that is to say they, are not brought about by linkage disequilibrium. The susceptible alleles DPB1*0201 and DR5 show evidence for interaction in the pathogenesis of EOPA-JCA. Interaction seems likely between DPB1*0201 and DRB1*08, DR5 and DRB1*08, or between DR6 and DRB1*08. The strongest interaction exists between DPB1*0201 and a common DQ factor associated with both DR5 and DRB1*08. Finally, we observed a hierarchy among the various marker combinations, where the risk of developing EOPA-JCA increases with the number of associated markers present in an individual.
Alleles↗
Polymorphism of the tumor necrosis factor beta gene in systemic lupus erythematosus: TNFB-MHC haplotypes.
We investigated the Nco I restriction fragment length polymorphism (RFLP) of the tumor necrosis factor beta (TNFB) gene in 173 patients with systemic lupus erythematosus (SLE), 192 unrelated healthy controls, and eleven panel families, all of German origin. The phenotype frequency of the TNFB*1 allele was significantly increased in patients compared to controls (63.6% vs 47.1%, RR = 1.96, p < 0.002). The results of a two-point haplotype statistical analysis between TNFB and HLA alleles show that there is linkage disequilibrium between TNFB*1 and HLA-A1, Cw7, B8, DR3, DQ2, and C4A DE. The frequency of TNFB*1 was compared in SLE patients and controls in the presence or absence of each of these alleles. TNFB*1 is increased in patients over controls only in the presence of the mentioned alleles. Therefore, the whole haplotype A1, Cw7, B8, TNFB*1, C4A DE, DR3, DQ2 is increased in patients and it cannot be determined which of the genes carried by this haplotype is responsible for the susceptibility to SLE. In addition, two-locus associations were analyzed in 192 unrelated healthy controls for TNFB and class I alleles typed by serology, and for TNFB and class II alleles typed by polymerase chain reaction/oligonucleotide probes. We found positive linkage disequilibrium between TNFB*1 and the following alleles: HLA-A24, HLA-B8, DRB1*0301, DRB1*1104, DRB1*1302, DQA1*0501, DQB1*0201, DQB1*0604, and DPB1*0101. TNFB*2 is associated with HLA-B7, DRB1*1501, and DQB1*0602.
Base Sequence↗
No direct correlation between HLA-DPB1 and antibodies against recombinant Ro (SS-A)/La (SS-B) proteins in systemic lupus erythematosus. SLE Study Group.
We investigated the association of HLA-DPB1 alleles with the occurrence of autoantibodies against Ro (SS-A) or La (SS-B) using recombinant 52 kD-Ro, 60 kD-Ro and La proteins in 177 German patients with systemic lupus erythematosus (SLE). A significant increase in the frequency of DPB1*0101 is observed in SLE patients compared to healthy controls (Pcorr.. < 0.004). Antibodies against 52 kD-Ro, 60 kD-Ro and La are tested by ELISA and are found with a frequency of 25.4%, 33.9% and 17.5% in the patients, respectively. An association with HLA-DPB1*0101 is observed for antibodies against La (P < 0.01) and 52 kD-Ro (P < 0.01), but not for 60 kD-Ro in the absence of La/52 kD-Ro. Since there is a strong linkage disequilibrium between DPB1*0101 and DR3 in the normal population and in SLE patients, and since there is an association between DR3 and SLE, as well as between DR3 and the occurrence of recombinant Ro/La antibodies in SLE patients, we investigated whether DPB1*0101 is associated per se or via linkage disequilibrium with DR3. DPB1*0101 in the absence of DR3 is not more common in patients than in controls and not in patients with autoantibodies to Ro and La than without autoantibodies. We conclude that there is no evidence for a direct involvement of DPB1*0101 in the production of Ro/La autoantibodies in SLE patients.
Alleles↗
Class I associations and frequencies of class II HLA-DRB alleles by RFLP analysis in children with rheumatoid-factor-negative juvenile chronic arthritis.
A total of 94 patients with juvenile chronic arthritis (JCA) was tested for HLA class I by serology and for class II by RFLP typing. Early onset JCA (EOPA) is associated with HLA-A2, DR5 and DR8 in both males and females. The combination (joint occurrence) of these JCA associated alleles (A2, DR5, DR8) is frequently seen in patients with chronic iridocyclitis. Late onset pauciarticular disease has an increased frequency of HLA-B27, especially in males. Our data confirm that polyarticular JCA with early childhood onset (< or = 4 years) is associated with DR5 and DR8 and has a different immunogenetic background from polyarticular JCA with later childhood (> 4 years) onset (associated with DR4).
Adolescent↗
Effect of antihypertensive drugs on glomerular hyperfiltration and renal haemodynamics. Comparison of captopril with nifedipine, metoprolol and celiprolol.
Glomerular hyperfiltration and hypertension may contribute to the progression of chronic renal insufficiency regardless of the underlying disease. Protein restriction and antihypertensive treatment are used to slow the decline in renal function. However, little is known about the interaction of protein loading and antihypertensive treatment on glomerular haemodynamics in humans. This paper compares the renal haemodynamic effects of beta-adrenoceptor blockers with those of the calcium channel antagonist nifedipine and the ACE inhibitor captopril on resting glomerular filtration and during glomerular hyperfiltration. In two separate studies the effects of nifedipine, captopril, metoprolol, and celiprolol on renal haemodynamics have been investigated. In two groups of healthy volunteers (n = 13) inulin and PAH clearances were measured, first under fasting conditions and afterwards during aminoacid infusion. In fasting subjects nifedipine and metoprolol induced glomerular hyperfiltration, while celiprolol and captopril did not significantly affect GFR. Without premedication, and also after nifedipine, metoprolol and celiprolol, the aminoacid infusion significantly increased the GFR. After premedication with captopril, however, aminoacid-induced hyperfiltration was prevented. In fasting subjects captopril, celiprolol and metoprolol elevated PAH clearance. With our without premedication aminoacid infusion increased renal plasma flow compared to baseline on the control day. We conclude that in healthy subjects, acute administration of antihypertensive drugs results in different renal haemodynamic responses. In contrast to captopril and celiprolol, nifedipine and metoprolol induce glomerular hyperfiltration like protein loading. Thus, they may counteract the renal haemodynamic effects of protein restriction. Celiprolol behaves similarly to captopril, since it increases renal perfusion without inducing glomerular hyperfiltration, a pattern which might reflect lower glomerular pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Antihypertensive Agents↗
Measurement of insulin-like growth factor I (IGF-I) in normal adults, patients with liver cirrhosis and acromegaly: experience with a new competitive enzyme immunoassay.
A competitive enzyme immunoassay for the determination of human insulin-like growth factor I in microtiter plates was established. Using a polyclonal antiserum raised in rabbits against hIGF-I ovalbumin conjugate the assay system was able to detect IGF-I at a range of 12-800 pg/well with a sensitivity of 10 pg/well. It showed a low (< 0.5%) cross reactivity with hIGF-II. The serum concentrations of IGF-I found by EIA agreed well with those found in a conventional RIA (r = 0.965, p < 0.001). Effects of age and sex on IGF-I levels were studied in 260 normal adults. There was no evidence for sex differences but a steep decline of values from the third to the fourth and from the eight to the ninth decade, respectively. To asses the diagnostic capability of the IGF-I determination in liver cirrhosis, 71 sera of patients classified according to Child classes (A-C) were measured. Although significantly diminished concentrations were found in class B vs A and in class C vs B, the diagnostic sensitivity in cross-sectional examinations proved to be low (class A: 0.33, class B: 0.67). Only in the case of extensively destroyed liver parenchyma (Child C: 0.94) IGF-I was a good indicator of impaired hepatocellular capacity. In 29 patients with acromegaly serum IGF-I levels were investigated. All patients with active acromegaly showed increased IGF-I levels. In contrast, in inactive or weakly active acromegaly values were considerably lower.(ABSTRACT TRUNCATED AT 250 WORDS)
Acromegaly↗
Planar and SPECT imaging with technetium-99m labeled antigranulocyte antibodies in bone and soft tissue infection.
Scintigraphy with technetium-99m labeled antigranulocyte antibodies including planar and SPECT imaging demonstrated areas of inflammation in bone and soft tissue of the thigh of a 38-year-old man who had a fracture of the femur 20 years earlier. The clinical potential of this imaging modality in the diagnostic assessment of inflammatory diseases is discussed.
Adult↗
DNA typing for HLA-DPB1-alleles in German patients with systemic lupus erythematosus using the polymerase chain reaction and DIG-ddUTP-labelled oligonucleotide probes. Members of SLE Study Group.
Genomic DNA of 178 German Caucasian patients with systemic lupus erythematosus are studied for HLA-DP locus by using PCR and DIG-ddUTP-labelled oligonucleotide probes. A significant increase of DPB1*0101 is observed in SLE patients compared with healthy controls (chi 2 = 15.27, p.c. < 0.004). DPB1*0501 and *0901 are also slightly increased (chi 2 = 5.85, P < 0.05, p.c. = NS; chi 2 = 5.64, P < 0.05, p.c. = NS). There is no significant difference in frequency of DP alleles between male and female patients. Since a linkage disequilibrium between HLA-B, DR and DP loci is found in our SLE patients, an analysis is performed assessing the relative importance of these HLA-markers to SLE. The results show that the increase of DPB1*0101 in SLE patients is associated with the HLA-B8, DR3 haplotype and it suggests a more important role for HLA-B8, DR3 or genes within this haplotype than for DPB1*0101 in the genetic predisposition for SLE.
Alleles↗
Effect of local low-dose thrombolysis on clinical outcome in acute embolic renal artery occlusion.
PURPOSE: To determine the utility of local thrombolysis in treatment of acute embolic renal artery occlusion. MATERIALS AND METHODS: Fourteen patients with acute embolic renal artery occlusion treated with local low-dose thrombolysis were studied. Diagnosis was made with renal scintigraphy and selective renal arteriography. RESULTS: Thrombolysis was successful in 13 of 14 patients. During 1-72 months of follow-up (mean, 27.1 months), renal function did not improve on the side of complete renal artery occlusion, whereas stabilization of renal function at the pretherapy level was seen in patients with incomplete obstruction of the renal artery or complete obstruction at the level of segmental branches. In none of the patients did renal function return to normal. CONCLUSION: In acute embolic renal artery occlusion, thrombolytic therapy does not restore renal function and is therefore not indicated once the ischemic tolerance of the kidney (approximately 90 minutes) has been exceeded.
Acute Kidney Injury↗
Drug dosage in patients during continuous renal replacement therapy. Pharmacokinetic and therapeutic considerations.
The advantages of continuous haemofiltration and haemodialysis over intermittent haemodialysis for the treatment of acute renal failure are well recognised. In intensive care patients, 4 different continuous procedures, arteriovenous and venovenous haemofiltration (CAVH and CVVH) or haemodialysis (CAVHD and CVVHD), are employed. These effective detoxification treatments require knowledge of their influence on drug disposition. Data on kinetics of drugs during continuous treatment are scarce and limited almost exclusively to the oldest and least effective procedure (CAVH). Selected dialysis membranes may adsorb drugs, as in the case of aminoglycosides. In addition, elimination of substances with large molecular weights may vary depending on the pore size of the membrane, as in the case of vancomycin. Thus, even if drug dosages can be based on pharmacokinetic studies, selection of a dialysis membrane not studied may cause unpredictable drug concentrations. With these limitations in mind and considering the available literature on pharmacokinetics in patients with renal failure, general guidelines for drug dosage during continuous renal replacement therapy can be given. In haemofiltration, drug protein binding is the major factor determining sieving, i.e. the appearance of the drug in the ultrafiltrate. In haemodialysis, diffusion is added to ultrafiltration, and therefore the saturation of the combined dialysate and ultrafiltrate will decrease further with increasing dialysate flow rate. In continuous haemofiltration or haemodialysis the extracorporeal clearance can be calculated by multiplying the saturation value (estimated or, better, measured) with the ultrafiltrate and dialysate flow rate. Dividing the extracorporeal clearance by the total clearance (including the nonrenal clearance) gives the fraction of the dose removed due to extracorporeal elimination. Whether dosage recommendations available for anuric patients have to be modified or not can be decided on the basis of this value. In case of high nonrenal clearance, the degree of saturation is without clinical significance. Based on these considerations guidelines have been constructed for the effect of extracorporeal elimination on more than 120 different drugs commonly used in intensive care patients.
Drug Therapy↗
[Histology and puncture cytology of malignant tumors of the thyroid gland in childhood and adolescence].
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Adenocarcinoma, Follicular↗
Obesity in kidney transplant patients as a risk factor.
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Body Mass Index↗
Pharmacokinetics and pharmacodynamics of antistaphylococcal antibiotics in continuous ambulatory peritoneal dialysis patients.
Staphylococci are the leading pathogens in continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. Vancomycin appears to be an outstanding antistaphylococcal drug because resistance to it is nearly absent. The pharmacokinetics of vancomycin and clinical cure rates of peritonitis with different dosing guidelines have been studied extensively. Different dosing guidelines with IP or IV loading doses followed or not followed by IP maintenance doses are used successfully, despite the fact that some of the dosing schemes produce apparently suboptimal drug levels referring to in vitro data like the MIC value (minimum inhibitory concentration). Alternatively, aminoglycosides, cephalosporins, isoxazolyl penicillins, and broad-spectrum penicillins combined with beta-lactamase inhibitors may be used for the treatment of gram-positive peritonitis. For the above penicillins pharmacokinetic data are scarce, and clinical experience is limited. Rifampin has excellent intracellular antistaphylococcal activity and should be used in combination with other antibiotics. Although pharmacokinetic data are lacking, rifampin dosages do not require adaptation to renal function or replacement therapy.
Anti-Bacterial Agents↗
Renal functional reserve in elderly patients.
The concept of renal functional reserve (RFR) is used in the evaluation of renal function in health and disease. RFR is defined as the difference between glomerular filtration rate (GFR) at rest and the maximum GFR for example under stimulation by an amino acid infusion or a protein rich meal. GFR decreases normally with age by about 1 ml/min per year. The purpose of this study was to establish the effect of the GFR decrease with age on absolute and relative values of RFR. We investigated 12 hospitalized patients 60 to 85 years of age (mean 74 +/- 2.0 SEM) recovering from nonrenal disease. On two consecutive days, inulin and paraaminohippuric acid (PAH) clearance was performed over a period of 4 hours. On day A patients received 1 liter of a 5% glucose solution i.v. On day B an equal volume of an amino acid solution (2 mg/kg/min) was given. In these elderly patients baseline GFR without stimulation measured 73.2 +/- 7.9 ml/min per 1.73 m2 and stimulated GFR was 99.1 +/- 8.5 ml/min, a 35.3% increase (p < 0.025). Thus, renal functional reserve measured 25.9 +/- 8.7 ml/min. PAH clearance increased from 329.0 +/- 41.9 ml/min per 1.73 m2 to 438.8 +/- 50.3 ml/min (p < 0.025). These data confirm that baseline GFR is lower in the elderly compared to young adults. However, renal functional reserve is well maintained in elderly human subjects. This suggests that glomerulosclerosis of aging may not be the only explanation for the low baseline GFR in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
[Non-enzymatic marking of gene probes using digoxigenin for the diagnosis of sickle cell mutation and beta thalassemia].
A method is described in which allele-specific oligonucleotides (ASO) are labeled non-enzymatically with digoxigenin (DIG). The ASOs were synthesized in a DNA synthesizer. A primary C6-alkylamine was incorporated at the 5'end of the ASO. The derivative was coupled to digoxigenin-3-0-methylcarbonyl-epsilon-aminocaproic acid-N-hydroxy-succinimide ester. The DIG-ASO probes were isolated from the crude preparation and hybridized with amplified genomic DNA. The annealed probes were detected with an ELISA test. The DIG-ASO probes were successfully used for the identification of sickle cell disease genotypes and the most common beta-thalassemia mutations.
Adult↗
Rebound of plasma vancomycin levels after haemodialysis with highly permeable membranes.
Vancomycin is usually given only once a week to haemodialysis (HD) patients. If highly permeable dialysis membranes are used, however, high clearance values have been reported, so the aim of the study was to determine whether high clearance of vancomycin resulted in sufficient drug elimination to induce subtherapeutic plasma levels after one week. In 18 chronic HD patients, treated with polysulfone dialyzers (1.2 m2), the pharmacokinetics of vancomycin were studied after administration of 1 g. Concentrations were determined by fluorescence polarisation immunoassay. At a blood flow of 219 ml.min-1, HD clearance of vancomycin was 62.3 ml.min-1. Immediately after dialysis plasma concentrations were 38% lower than predialysis levels. However, marked rebound in the vancomycin level was observed 5 h later, resulting in plasma levels only 16% lower than prior to dialysis. 3 HD treatments in 1 week removed about one third of the initial dose. After one week 15 of 18 patients still had a therapeutic plasma level (greater than 4 micrograms.ml-1). In conclusion, polysulfone membranes show high clearance of vancomycin. However, transfer of drug from blood to dialysate appears to be faster than from tissues to blood. Because of a marked rebound in plasma level after treatment, therapeutic drug concentrations will still be present in most patients after one week.
Female↗