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Biomedical subjects

A M Luger

Publications and source records attributed to A M Luger.

At least 37 records · Page 2Linked to original sources

Molecular and serologic analysis of HLA genes and immunoglobulin allotypes in IgA nephropathy.

We studied a large North American Caucasian population of patients with biopsy proven IgA nephropathy for polymorphisms of HLA-A,B,C, HLA-DR, HLA-DQ and HLA-DP using a combination of serologic phenotyping and polymerase chain reaction sequence specific oligonucleotide probe (PCR-SSOP) hybridization genotyping. We also examined patients for polymorphisms of immunoglobulin by determining Gm and Km allotypes. When compared to healthy local controls there was an apparent decrease in HLA-DR5 (DRw11, DRw12) suggesting that this allele had a protective effect on disease susceptibility. None of the previously reported HLA-DQ associations found among Japanese or british Caucasian patients were found among this large North American Caucasian population. The HLA-DPB1*0601 genotype was increased among patients, but this was not significant when corrected for multiple comparisons. There were no differences in the distribution of Gm or Km allotypes among patients versus controls, regardless of whether they were stratified into those with progressive or non-progressive renal disease. Taken together, these findings suggest that there is substantial genetics heterogeneity in susceptibility to IgA nephropathy among different ethnic and/or geographically distinct populations.

Alleles↗

An evaluation of the renal protective effect of manidipine in the uninephrectomized spontaneously hypertensive rat.

The effects of calcium antagonism on the development and progression of renal disease are controversial. To address this problem, studies were performed on young, uninephrectomized spontaneously hypertensive rats (SHRs) with the dihydropyridine calcium antagonist, manidipine, to assess its effect on the early pathogenesis of focal glomerulosclerosis. Male SHRs underwent uninephrectomy at age 10 to 11 weeks and were subsequently assigned to no treatment (control), a predetermined subvasodepressor (low) dose of manidipine (2.5 mg/kg body weight), or a predetermined antihypertensive (high) dose of manidipine (20 mg/kg body weight). All animals received a diet containing 0.4% sodium and 23% protein. Serial determinations of body weight, systolic tail cuff pressure, and 24-hour urinary excretion of creatinine, sodium, and protein (UprotV) were made at 1- to 6-week intervals, for a total treatment period of 12 weeks. In final experiments plasma was obtained for creatinine, angiotensin I, and angiotensin II determinations, and renal tissue was harvested for histologic and morphometric analysis. Compared with the untreated control, low-dose manidipine therapy had no effect on body weight, systolic blood pressure, creatinine clearance, UprotV, renal histologic findings, glomerular volume, or plasma angiotensin I or II concentrations. In contrast, high-dose manidipine therapy decreased systolic blood pressure from 194 +/- 3 to 160 +/- 4 mm Hg (p < 0.01). Creatinine clearance and UprotV were unchanged. Although body weight was not different, kidney weight was higher. However, mean glomerular volume was lower. More importantly, the prevalence of mesangial expansion with proliferation was lower: 6.7% (control) versus 2.8% (high-dose manidipine) (p < 0.01). Finally, plasma angiotensin I and angiotensin II concentrations did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Familial unilateral renal agenesis and focal and segmental glomerulosclerosis.

Renal dysplasia and agenesis may be a familial disorder. We report the familial occurrence of unilateral renal agenesis and proteinuria that, at least in one case, was related to focal glomerulosclerosis. Whether these abnormalities are related to an intrinsic abnormality in the remaining kidney, hyperfiltration injury, systemic hypertension, or some other poorly defined factor is unclear at present. However, this report, along with previous case reports of familial renal agenesis, suggests that ultrasonographic screening of first-degree relatives of patients with renal agenesis is appropriate. Whether treatments such as dietary protein restriction, use of angiotensin-converting enzyme inhibitors, or other therapeutic interventions will have a beneficial effect in asymptomatic individuals with unilateral renal agenesis remains to be determined.

Adult↗

Human autoantibodies against the 70-kd polypeptide of U1 small nuclear RNP are associated with HLA-DR4 among connective tissue disease patients.

Serum samples from patients with connective tissue disease (CTD) were characterized using a recently developed enzyme-linked immunosorbent assay for reactivity with individual specific polypeptides of U1 small nuclear ribonucleoproteins, including the U1-70-kd protein. The distribution of HLA antigens was compared in CTD patients with and in those without anti-U1-70-kd autoantibodies and in normal controls. The frequencies of HLA-DR4 and HLA-DRw53 were increased among the anti-U1-70-kd autoantibody positive CTD group compared with the frequencies in anti-U1-70-kd autoantibody negative systemic lupus erythematosus patients and compared with normal controls. We conclude that the presence of autoantibodies reactive with the anti-U1-70-kd protein antigen is associated with HLA-DR4 and HLA-DRw53.

Antibodies, Antinuclear↗

Cost effectiveness and accuracy of renal scans in the management of patients undergoing renal transplantation.

Following renal allograft transplantation, renal scans are frequently performed to evaluate anatomical and functional causes for allograft dysfunction. In our retrospective study of 20 patients, renal scans were found to be more expensive compared to renal biopsies $68,688 vs $7,421, and, in only one patient was aggressive anti-rejection therapy instituted based solely on the renal scan results. The 95% confidence interval for the proportion of correct diagnosis by renal scan was 0.16 to 0.62.

Adult↗

Systemic mastocytosis associated with membranous nephropathy and peripheral neuropathy.

A report of the occurrence of membranous nephropathy and peripheral neuropathy in a patient with systemic mastocytosis is presented. Previous reviews of patients with systemic mastocytosis have not noted this association. During cyclical therapy with prednisone and chlorambucil in this case, nephrotic-range proteinuria remitted. Peripheral neuropathy resolved 10 months after discontinuation of therapy. Pathophysiological mechanisms resulting in this clinical presentation may be immunologically mediated.

Demyelinating Diseases↗

Universal spondylodiscitis in a patient with erosive peripheral arthritis and apatite crystal deposition.

A patient with erosive peripheral arthritis in whom vasculitis and monoclonal IgG kappa paraprotein were associated with sacroiliitis and widespread destruction of intervertebral discs is reported. Crystals resembling apatite were identified in intervertebral disc material, and we postulate that the discitis was accelerated by apatite deposition. Our case illustrates a unique example of axial involvement in rapidly progressive joint disease.

Adult↗

Poststreptococcal glomerulonephritis in the elderly. Report of a case and review of the literature.

Acute poststreptococcal glomerulonephritis (PSGN) is uncommonly seen in the elderly population and its diagnosis is not without some difficulty because clinical manifestations may mimic other diseases. Renal biopsy for diagnosis and early intervention, if indicated, is very valuable in such a situation. We present here a case of an elderly patient with PSGN and a review of the literature. In addition to the typical clinical manifestations of the disease, dyspnea and pulmonary congestion are commonly present in elderly patients, probably a result of excessive salt and water retention in the face of compromised cardiovascular function. Elderly patients with PSGN appear to have a remarkably poor prognosis, with significant incidences of acute mortality and chronic renal disease. Our patient had the unusual finding of a large number of glomerular crescents with near complete clinical recovery after short-term follow-up.

Aged↗

Prediction of crossmatch outcome in highly sensitized dialysis patients based on the identification of serum HLA antibodies.

High levels of allosensitization (greater than 50%), which often occur in dialysis patients awaiting renal transplant, make donor selection difficult. Such patients may be included in elaborate protocols in which they are crossmatched with all available ABO compatible donors, or crossmatching may be deferred until a very-well-matched donor becomes available. The former approach of random crossmatching is costly and inefficient, while the latter approach may overlook crossmatch-compatible donors. We believe that the identification of antibodies present in highly reactive sera and the use of this information in donor selection would increase the frequency of crossmatch-negative donors for these patients. In this study eleven sera, reactive with 70% to 100% of a random cell panel, were obtained from multiply transfused dialysis patients. Sera were analyzed by standard (CDC) and antiglobulin augmented (AHG-CDC) lymphocytotoxicity, and by differential absorption with HLA-typed platelets. All sera contained only one or two antibodies directed against the high frequency public HLA epitopes, accounting for 85% to 100% of each serum's total reactivity. These characterized sera were crossmatched with 114 random normal donors. The frequency of negative crossmatches was 20.5%. However, if the serum antibody data had been used to preselect donors for crossmatch--that is, to exclude donors that were likely to be positive--the negative crossmatch frequency would have increased to 86.4%. The use of the serum analysis data in donor selection would have reduced the total number of required crossmatches by 78%. Serum analysis correctly predicted the outcome of 95.6% of crossmatches performed with an average of 3% false positives and 1.3% false negatives. This approach to donor selection reduces unnecessary crossmatching and increases the likelihood of finding crossmatch-compatible donors for highly reactive patients.

ABO Blood-Group System↗

Cowden disease: gene marker studies and measurements of epidermal growth factor.

Cowden disease (CD) is a familial syndrome characterized by tumors of the skin, oral mucosa, breast, thyroid, and intestinal epithelium. Since the syndrome is inherited as an autosomal dominant, we examined a battery of gene markers in a family with CD to detect linkage between the CD gene and known marker genes. There was no positive evidence for linkage of a CD locus with any of the markers; other investigators can add to our data to confirm and extend these findings. Additionally, we measured epidermal growth factor (EGF) in body fluids from CD patients and controls to determine if elevated EGF levels might be responsible for the widespread epithelial proliferation in CD. EGF levels in saliva, serum, plasma, and urine were similar in CD patients and control subjects. Although alterations in growth factors or their receptors may play a role in CD, excess circulating EGF is not responsible for the manifestations of the syndrome.

Adult↗

Ciliated adenocarcinoma of the endometrium.

Two cases of ciliated endometrial adenocarcinoma which came to attention in less than one year are described. This entity deserves emphasis, as its ciliation may distract from its histological malignant features. Association of cilia with atypical nuclear features in the same cell is the diagnostic characteristic which distinguishes it from non-ciliated adenocarcinoma overrunning non-malignant ciliated endometrium. The ultrastructural detail of the cilia of malignant cells does not differ from that of non-malignant endometrial glandular epithelium. Our cases raise the question of a possible association of estrogenic effect with ciliated endometrial adenocarcinoma.

Adenocarcinoma↗