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Biomedical subjects

R G Horn

Publications and source records attributed to R G Horn.

At least 19 recordsLinked to original sources
PubMed1997

A 51-year-old woman with nephrotic syndrome, hematuria, and renal insufficiency.

This case illustrates the utility of all modalities of the renal biopsy in arriving at a correct diagnosis in an adult patient with nephrotic syndrome. Unlike the clinical situation in children, where minimal change disease is presumed to underlie the nephrotic syndrome unless the patient shows steroid resistance, the list of differential diagnosis of nephrotic syndrome in the adult is lengthy. The renal biopsy is essential in establishing the specific diagnosis. We discuss the diagnostic approach in an adult patient with a relatively uncommon disease causing the common manifestations of nephrotic syndrome, hematuria and renal insufficiency.

Biopsy↗
PubMed1996

Angiotensin converting enzyme gene polymorphism: potential silencer motif and impact on progression in IgA nephropathy.

Since the renin angiotensin system (RAS) is established as an important factor in renal disease progression, we determined whether RAS alleles that have been linked to variability in outcome in several cardiovascular diseases also affect progression of IgA nephropathy. These genetic variants include: (1) angiotensin I converting enzyme deletion polymorphism in intron 16 (ACE I/D), reported to be associated with increased risk of myocardial infarction as well as left ventricular hypertrophy; (2) a point mutation in the angiotensinogen (Agt) gene resulting in a methionine to threonine substitution at residue 235 (M235T), reported to be associated with hypertension in Caucasians; and (3) an angiotensin receptor type I (ATR) A to C transition at bp 1166 (A1166C) which shows synergy with the deleterious effects of the ACE DD genotype in myocardial infarction. We examined these polymorphisms by PCR amplification of genomic DNA samples from 64 Caucasian patients in the USA (age 6 to 83 years) with biopsy-proven IgA nephropathy whose renal status was followed for an average of almost seven years. Patients who presented with and maintained normal serum creatinine (Cr, < 1.5 mg/dl), had ACE genotype frequencies of II:35%, ID:61%, DD:4%. By contrast, in patients with progression (initially normal Cr increased to a mean of 4.5 +/- 0.86 mg/dl), ACE genotype frequencies were II:22%, ID:44%, DD:33% (P = 0.057 by Fishers's exact test, vs. non-progressors). The association of the DD genotype with progression was even more striking when patients with other risk factors (hypertension and/or heavy proteinuria) were excluded. In this subgroup, the genotype frequencies in patients with stable creatinine versus those with deterioration in renal function was 53%, 47%, and 0% versus 0%, 40%, and 60%, respectively, for II, ID, and DD genotypes (P = 0.009 by Fisher's exact test, progressors vs. non-progressors). Further, sequence analysis of the I gene polymorphism revealed a potential 13 bp silence motif. Neither the Agt 235T nor the ATR A 1166C gene variants, however, was associated with deterioration of renal function. Taken together, these results indicate that, although polymorphism in each of the three genes in the RAS system has been linked to cardiovascular diseases, only the ACE I/D polymorphism is associated with progressive deterioration in renal function in IgA nephropathy. Since previous observations link ACE polymorphism with ACE activity, these findings imply a widespread importance of ACE in modulating destructive processes in different organs.

Alleles↗
PubMed1995

Is focal segmental glomerulosclerosis really focal? Distribution of lesions in adults and children.

The distribution of lesions of glomerulosclerosis, whether focal or diffuse, has important implications for pathogenesis and potential therapeutic response. Determination of focal or diffuse nature of lesions from a single section, may, however, be misleading. We therefore evaluated the distribution of segmental glomerulosclerosis in patients with nephrotic syndrome and idiopathic focal segmental glomerulosclerosis (FSGS) by three-dimensional analysis. From our files, we identified all such biopsies with a diagnosis established by immunofluorescence, electron microscopy, and light microscopy that had > 10 glomeruli and serum creatine < 3.5 g/dl. Renal biopsies from 15 adults (9 women, 6 men, age 40.3 +/- 4.2 years and six children (2 girls, 4 boys, age 6.3 +/- 1.4 years) thus identified had sufficient serial sections for analysis. An average of 20.0 +/- 2.6 glomeruli in adults versus 25.2 +/- 3.9 in children were examined. Sclerosis assessed on a single section involved 31.5 +/- 6.8% of glomeruli in adults, contrasting only 11.7 +/- 5.7% in children (P < 0.05). Complete serial section analysis was possible in 14.1 +/- 1.6 and 10.7 +/- 1.6 glomeruli in adults and children, respectively. After this serial section analysis, the percent of glomeruli involved by sclerosis increased to 48.0 +/- 6.6% in adults and 23.2 +/- 7.4% in children (P < 0.025). The pattern remained focal in all but one case that had the highest serum creatinine. The greater increase in sclerosis after serial section analysis in children versus adults reflects the predominance of small peripheral, that is, more segmental, lesions in children than adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Morphologic and clinical features of fibrillary glomerulonephritis versus immunotactoid glomerulopathy.

Renal diseases characterized by Congo red-negative extracellular fibrillary deposits, either organized arrays of larger, microtubular fibrils (immunotactoid glomerulopathy [IT]) or smaller, randomly organized fibrils (fibrillary glomerulonephritis), have been recognized recently. The clinical significance, if any, of the distinction of these patterns has not been determined. On review of all renal biopsy specimens evaluated in a private referral renal pathology laboratory over the last 11 years, 26 cases with fibrillary glomerulonephritis pattern were identified and compared with our six most recent cases with the IT pattern. The fibrillary glomerulonephritis patients, 17 women and nine men, had an average age of 50 +/- 2 years and contributed 1% of the renal biopsy specimens examined. All patients had marked proteinuria and 16 had microscopic hematuria. Follow-up at 23 +/- 5 months in 25 of these patients revealed end-stage renal disease in 11 patients (44%) and one death due to renal failure. End-stage renal disease developed an average of 10 +/- 5 months after biopsy. One patient developed multiple myeloma. Twenty-four renal biopsy specimens showed proliferation, with crescents in seven. Immunofluorescence showed moderate to intense staining for immunoglobulin G and weaker staining for C3, in a predominantly mesangial pattern, with weaker glomerular basement membrane (GBM) staining, corresponding to electron microscopic deposit localization. In four cases, linear GBM staining by immunofluorescence corresponded to extensive subendothelial or transmembranous deposits. The average fibril diameter was 14.0 +/- 0.5 nm (range, 10.4 to 18.4 nm). Immunotactoid glomerulopathy patients (three women and three men) were significantly older, 62 +/- 2 years (P < 0.025). All had marked proteinuria, with microscopic hematuria in two patients. Associated hematopoietic diseases were present in four patients, with monoclonal proteins and/or abnormal plasma cell proliferation in three. One patient died of nonrenal causes. The remaining five patients have stable renal function at 20 +/- 5 months. Biopsy specimens showed proliferative (n = 3) or membranous-like (n = 3) patterns. Immunofluorescence showed immunoglobulin G and weaker C3 staining in a granular GBM pattern, with lesser mesangial staining. The microtubular fibril diameter was on average 43.2 +/- 10.3 nm (range, 16.8 to 90.0 nm). Thus, fibrillary glomerulonephritis and IT can be separated based on ultrastructurally distinct features. Patients with fibrillary glomerulonephritis are less likely than those with IT to have associated hematopoietic disease and also have poorer renal survival. We propose that classification based on these morphologic differences appears to have clinical significance.

Adult↗
PubMed1979

An electron microscopic India ink technique for demonstrating capsules on microorganisms: studies with Streptococcus pneumoniae, Staphylococcus aureus, and Neisseria gonorrhoeae.

A technique using India ink in electron microscopic preparations was used to study bacterial capsules. Capsules were demonstrated on Streptococcus pneumoniae and Staphylococcus aureus (strain M and the Smith diffuse variant) from in vitro cultures. Two types of false capsules were observed on Neisseria gonorrhoeae grown in vitro or obtained from human urethral exudates. No true capsules were definitively identified on gonococci from these sources. The technique described does not require the use of specific anticapsular antibody or specific polysaccharide stains and permits the detection of artifacts that may, by the use of light microscopic methods, be misinterpreted as capsules.

Antigens, Bacterial↗
PubMed1979

Pili of Neisseria meningitidis: effect of media on maintenance of piliation, characteristics of Pili, and colonial morphology.

In contrast to information in the literature which indicates that meningococci rapidly lose pili upon cultivation in vitro, we found that piliation of meningococci could be maintained in vitro for 15 or more passages. Pili were present on all eight isolates tested, whether from asymptomatic carriers or from subjects with meningococcal disease. Complete loss of piliation occurred in the same two strains on two of the three media tested. On one medium (Thayer-Martin medium with supplement B), there was partial or complete loss of pili by all strains. The optimal medium for maintaining pili was chocolate agar with 1% IsoVitaleX; 95% or more of the microorganisms of six of the eight strains tested were piliated after 15 passages in vitro, and more than 60% of the microorganisms of the other two strains were piliated. Meningococci passed on this medium generally maintained their initial density of piliation (3 to 34 pili per diplococcus). The ability to predictably cultivate piliated meningococci in vitro and to select piliated and nonpiliated clones of the same strain should allow investigation of the biochemical and immunological properties of meningococcal pili as well as their possible role in the pathogenicity of Neisseria meningitidis.

Culture Media↗
PubMed1978

Nephrotoxicity from cancer immunotherapy.

Because systemic intravenous immunotherapy with Corynebacterium parvum is an effective immunopotentiating and immunotherapeutic agent in animals, clinical studies of this agent have been undertaken. Toxicities in man have been noted, but most are treated symptomatically. Three patients with metastatic melanoma developed oliguria, edema, diffuse bilateral pulmonary infiltrates, azotemia, hypoalbuminemia and hypocomplementemia, while receiving intravenous C. parvum therapy. All had renal biopsies that showed a proliferative glomerulonephritis with subendothelial basement membrane deposits. Immunofluorescence showed glomerular IgG, IgA, IgM, and the C3 component of complement. A fourth patient was found in retrospective chart review of 87 patients registered on two C. parvum-containing protcols. The frequency of the complication in this group was 3/87. Renal failure resolved in all four patients spontaneously after the cessation of C. parvum immunotherapy. Serial evaluation of renal function should be carried out in all patients on systemic adjuvant immunotherapy.

Adult↗
PubMed1978

Characterization of feline glomerulonephritis associated with viral-induced hematopoietic neoplasms.

Light, electron, and immunofluorescence microscopy on tissues from 63 domestic cats revealed that glomerulonephritis occurred in almost one third of cats with hematopoietic neoplasms of the type linked with feline leukemia virus (FeLV). Glomerular lesions were of the immune complex type with subepithelial, subendothelial, and mesangial dense deposits and reticular aggregates, similar to the nephropathy associated with systemic lupus erythematosus in humans. Evidence that the glomerular lesions may be viral-induced raises the possibility of similar pathogenetic mechanisms in human disease.

Animals↗
PubMed1976

Unsuspected diabetic glomerulosclerosis.

Six patients without overt diabetes mellitus underwent renal biopsy for suspected glomerulonephritis. All were demonstrated to have diabetic glomerulosclerosis and subsequently were found to have abnormal glucose tolerance tests. Electron microscopy was critical in making the correct diagnosis in five of six patients. The reported cases represent 3% of a series of 200 patients who had a renal biopsy to evaluate possible glomerulonephritis. Renal manifestations of diabetes mellitus may antedate glycosuria and other more common presenting symptoms of this disease.

Adult↗
PubMed1976

Acute diffuse interstitial nephritis related to chemotherapy of tuberculosis.

Acute renal insufficiency developed in three patients receiving chemotherapy for tuberculosis. It is proposed that acute diffuse interstitial nephritis related to the drugs was responsible for the renal injury. Recovery of renal function was slow and incomplete. Physicians administering chemotherapy to patients with tuberculosis must be aware of the potential nephrotoxicity of the common treatment regimens.

Antitubercular Agents↗
PubMed1975

Malignant lymphomas of follicular center cell origin in man. I. Immunologic studies.

Lymphomas with histologic features indicating a follicular center cell (FCC) origin were analyzed from 26 patients of a group of 45 consecutive non-Hodgkin's lymphoma patinets whose tumors were studied for B- and T-cell characteristics. They were compared with benign, reactive lymphoid tissue from 14 patients. Cell suspensions from biopsy material, blood, or bone marrow were examined for surface Ig and for rosette formation with sheep erythrocytes (E rosettes). Of the 26 patients with FCC lymphomas, 22 had 40% or more Ig-bearing cells; all patients with FCC lymphoma tissues had 25% or less E rosette-forming cells. Cells from most FCC lymphomas of the cleaved type had surfac IgM; those from several FCC lymphomas had both IgM and IgD. Cells from lymphomas of noncleaved cell type had surface IgG or IgA. Light-chain analysis showed that cells from FCC lymphomas bore a predominant light-chain type, which indicated their monoclonal nature. Neoplastic cells from several FCC lymphomas synthesized the surface Ig which they bore. Reactive tissues usually contained fewer Ig-bearing and more E rosette-forming cells than FCC lymphomas; the Ig-bearing cells, with one exception, had a polyclonal distribution. Correlation of histologic and immunologic observations indicates that most lymphomas identified as FCC in origin by light micorscopic criteria mark as B cells with the use of immunologic techniques and that FCC lymphomas are the most common type of non-Hodgkin's lymphoma.

B-Lymphocytes↗
PubMed1975

Malignant lymphomas of follicular center cell origin in man. II. Ultrastructural and cytochemical studies.

Tissues from malignant lymphomas with both nodular and diffuse growth patterns, thought by light microscopy to be composed of cells of follicular center cell (FCC) origin, Were examined by electron microscopy; the tumor cells were similar to lymphoid cells found in reactive follicular centers. Tumor cells from neoplasms thought to be composed of cleaved FCC often had more pronounced nuclear folding than did cleaved FCC of reactive follicles, whereas cells in tumors of noncleaved FCC type were indistinguishable from their presumed counterparts in reactive follicles. Large cell noeplasms, previously classified as "histiocytic" lymphomas were composed of cells with ultrastructural characteristics of transformed lymphocytes; they showed neither ultrastructural nor cytochemical features of mononuclear phagocytes. These findings support the concept that a major group of lymphomas arises from lymphocytes of follicular centers.

B-Lymphocytes↗