Alkaptonuria and renal failure: a case report and review of the literature.

In alkaptonuric ochronosis, the absence of homogentisic acid oxidase results in the accumulation of homogentisic acid in the body. Associated renal failure is rare and usually occurs in the later stages of the disease. We report a 19-yr-old girl who presented initially with severe renal failure, without family or past history of illness. There was no significant proteinuria or hematuria. No clinical evidence of pigmentation such as skin and subcutaneous cartilages was noted. However, pigment deposits were identified in the renal biopsy specimens obtained within a week after admission and another after a month. Two months later the peritoneal dialysis fluid and skin progressively darkened, suggesting ochronosis. This was confirmed by the detection of homogentisic acid in the serum and urine. The patient expired in renal failure. Renal biopsy tissues showed diffuse chronic tubulo-interstitial disease characterized by widespread tubular atrophy, interstitial fibrosis, and a moderate degree of inflammation. Many tubular cells contained brown, coarsely granular ochronotic pigment (OP) and a few pigment casts were in the lumina. Similar deposits were also in the interstitium and within histiocytes. Ultrastructural studies of the glomeruli revealed small sparse OP deposits in the visceral and parietal epithelial cells, mesangial cells, and rare extracellular and basement membrane deposits. The tubulointerstitial changes were varied: atrophy and dilatation of tubules, varying degrees of lysosomal OP and degeneration of tubular cells, casts containing OP with crystalline material, histiocytes distended with OP, and free interstitial pigment deposition.(ABSTRACT TRUNCATED AT 250 WORDS)

The neutrophil response to polystyrene microspheres bearing defined surface functional groups.

Luminol-induced chemiluminescence (CL) and phagocytosis by human neutrophils was studied using polystyrene microsphere latices as particulate stimuli. Chemiluminescence and phagocytosis parameters were measured for particles bearing carboxyl, hydroxyl, and amino groups, as well as for the underivatized microspheres. The kinetic curves of CL were bimodal, and curve parameters were evaluated for both the early- and late-phase responses. Significant differences were found among the particle surfaces studied. Underivatized particles elicited the greatest response, particles with the amino group stimulated PMN the least, carboxyl- and hydroxyl-group-bearing particles elicited intermediate magnitudes of response. Phagocytosis data were in good agreement with that obtained from CL measurements. These data provide further evidence in favor of the hypothesis that, in protein-free systems, hydrophobic particles are more readily phagocytosed. Additionally they demonstrate that electrostatic interactions are not a significant factor for neutrophil-particle contact.

Renal papillary necrosis: relapsing form associated with alcoholism.

Described is a patient with recurrent renal papillary necrosis and chronic alcoholism as a possible precipitating factor. The case also demonstrates excellent recovery of renal function, despite considerable scarring of the parenchyma secondary to repeated episodes of sloughing of the papillae.

Stimulation of the hexose monophosphate pathway in the human erythrocyte by Mn2+: evidence for a Mn2+-dependent NADPH peroxidase activity.

In human RBC hemolysates, Mn2+ was found to stimulate the HMP as determined by the release of 14CO2 from [1-14C]glucose, providing activities of 125, 200, and 300% of basal at Mn2+ concentrations of 1, 10, and 100 mM, respectively. To explore the possibility that this stimulatory effect upon the HMP is a result of redox recycling of NADPH, RBC hemolysates were used to study NADPH oxidation. Mn2+, alone or in combination with a free radical-generating system, did not enhance the ability of hemolysates to oxidize NADPH. However, hemolysates + 10 mM H2O2 brought about a 10-fold increase in NADPH oxidation (0.51 +/- 0.05 nmole/min to 5.67 +/- 0.84 nmole/min) and the addition of 10 mM Mn2+ to this system increased the rate of oxidation to 34.10 +/- 2.97 nmole/min. Boiled hemolysates, either in the presence or absence of Mn2+, had some residual catalytic activity.

Differential immunoadsorption coupled with rate nephelometry for estimation of DNA-binding immunoglobulins.

We describe a technique for estimating the mass of anti-DNA antibodies by immunonephelometry of serum immunoglobulins (IgG, IgA, IgM) before and after adsorption onto DNA bound to agarose-polylysine columns. Sixteen patients with systemic lupus erythematosus and 16 age- and sex-matched controls were studied. Precision was determined for high-value (in 10 patients) and low-value (in nine controls) ranges for each of the immunoglobulins. Within-run CVs ranged from 3.0% (IgG, controls) to 11.8% (IgA, patients); between-run CVs ranged from 15.5% (IgG, patients) to 25.2% (IgM, patients). We found anti-DNA antibody concentrations (mean +/- SD) in systemic lupus erythematosus of 1.981 +/- 1.015 g/L for IgG (controls: 0.243 +/- 0.231, p less than 0.001), 0.257 +/- 0.215 g/L for IgA (controls: 0.038 +/- 0.035, p less than 0.001), and 0.282 +/- 0.234 g/L for IgM (controls: 0.191 +/- 0.165, p greater than 0.05). Sensitivity and linearity are such that fivefold dilutions of patients' serum with either a buffered albumin solution or control serum yielded values close to the expected values for IgG. Similarly diluted sera gave inordinately high values in the radiometric binding assay. Neither parametric (linear regression) nor nonparametric correlation methods (Spearman's rank and Kendall's tau) show a significant correlation between patients' data obtained by the present technique and that by a radiometric binding assay (p greater than 0.05), although combined data from patients and controls demonstrate a significant nonparametric correlation (p less than 0.005 for Spearman's and p less than 0.02 for Kendall's).

Water soluble vitamins in granulocytes, erythrocytes, and plasma obtained from chronic hemodialysis patients.

A granulocyte fraction, composed primarily of polymorphonuclear neutrophils, was harvested from six male and six female chronic hemodialysis patients receiving folate as their sole vitamin supplement. Cells were assayed for water soluble vitamins and levels compared with cells from 12 age- and sex-matched controls. Thiamin, riboflavin, and vitamin B6 and B12 levels were not significantly different from controls. In contrast, pantothenate and biotin were significantly increased while ascorbate and nicotinate were significantly reduced in dialysis patients. Neutrophil folylmonoglutamates were significantly increased in chronic hemodialysis patients, but after conjugase treatment no significant difference was observed. The erythrocytes and plasma from these two groups were also compared. In the erythrocytes of chronic hemodialysis patients, no vitamin deficiencies were observed. Significantly elevated levels of vitamin B12, riboflavin, biotin, and pantothenate were present in the patients, while thiamin, vitamin B6, nicotinate, and ascorbate were not significantly different from controls. In plasma, only ascorbate was significantly decreased in the patient group; biotin, riboflavin, and pantothenate were elevated. No significant difference was observed for vitamins B6, B12, and thiamin.

KB cells for antinuclear antibody determination: comparison with HEp-2 cells and the Crithidia luciliae assay.

Fifty-seven sera from 53 patients were assayed simultaneously on KB and HEp-2 cells and compared with regard to pattern and titer. Additionally, KB cell fluorescent antinuclear antibody (FANA) titer and pattern in 310 sera from 194 patients were compared with regard to the presence of antinative DNA antibodies (anti-nDNA ab) as determined by the Crithidia luciliae assay. Sixty-five percent (37/57) of the sera had the same titer on both KB and HEp-2 cells; the remainder had higher titers using KB cells. Regression analysis yielded a highly significant, unbiased correlation between the substrates. Forty-four percent (25/57) of these sera gave identical patterns on both substrates, another 25 of the 57 sera (44%) gave different patterns on the two substrates and 12% (7/57) could not be compared because they were negative on HEp-2 cells. KB cells detected positive FANA in 30 of 30 (100%) diagnosed cases of systemic lupus erythematosus; HEp-2 cells detected 29/30 (97%). From the standpoint of sensitivity, these data indicate a slight advantage to the use of KB over HEp-2 cells. Seventeen percent (53/310) of the sera were positive for anti-nDNA ab. The highest percentage of these positive sera occurs at reciprocal FANA titers between 320 and 1280. No association was found between KB FANA patterns and a positive Crithidia luciliae assay.

Cation complexed DNA. A novel class of immunoadsorbents for anti-DNA antibodies.

DNA can be precipitated as complexes with metal and organic cations. We have prepared these products using divalent metal cations (Cu2+, Mn2+, Ni2+, Zn2+, and Co2+) and ditetrazolium ions (blue tetrazolium and neotetrazolium). They are effective adsorbents, in vitro, for anti-nDNA antibodies and in reducing the titer of antinuclear antibodies in the sera from patients with autoimmune disease. They selectively adsorb most of the antinuclear components from a mixture of antimitochondrial and antinuclear antibodies.

The adsorption of bile salts on activated carbon.

Activated carbon (AC) has been shown to be effective in reducing serum cholesterol and triglycerides. The mechanism for this action is proposed to be a result of the removal of bile salts in the gut. In this paper, the adsorption of cholate, glycocholate, taurocholate, chenodeoxycholate and deoxycholate on AC is studied in vitro. The results indicate that AC has a high capacity for bile salts, completely removing them from solutions of up to 5 mM and at a rate consistent with physiological activity. Of the 2 types of AC tested, one was shown to exhibit greater capacity and selectivity over the other. A negligible effect was seen with variation of pH through the range 7-9. Desorption occurs in the presence of bile salt-free buffer, but to a minimal extent. Based on these data, the adsorption of bile salts by AC appears to be a likely mechanism for AC-induced reduction of serum lipids.

Imipramine for aspermia after lymphadenectomy.

During radical retroperitoneal lymphadenectomy the hypogastric sympathetic plexus is necessarily partially sacrificed, with resultant failure of part of the ejaculatory mechanism and aspermia. We have observed this condition to be reversible with imipramine.

Mechanism for transport of nitro-blue tetrazolium into viable and non-viable leukocytes.

The permeability of the membrane of phagocytic leukocytes (WBC) to the non-complexed nitro-blue tetrazolium (NBT) cation has not been well explored. In this study both complexed and non-complexed (or free) NBT have been incubated with viable cells. The entry of NBT into the WBC was determined by both colorimetric and infrared analyses. Very little free NBT enters the viable WBC compared with NBT complexed with serum factors. NBT entry was also studied in non-viable WBC by use of the infrared system. The entry of NBT into the non-viable cells was independent of serum complexing factors. Much larger quantities of both free and complexed NBT enter non-viable cells than enter viable WBC. It is concluded that the membrane of the viable WBC is quite impermeable to the free NBT cation. Ultrastructural studies suggest that the gaps in the plasma membrane of non-viable cells could allow the passage of relatively large amounts of both free and complexed NBT.

The two dimensional structure of tetrazolium-mucopolysaccharide complexes deduced from reactivity studies.

The formation of complexes between mucopolysaccharides and tetrazolium salts has been studied both by turbidimetry and nephelometry. The technique of laser nephelometry allows the detection of colloidal aggregates in systems which may, by turbidimetric methods, be ambiguous. The results indicate that binding of tetrazolium salts to polyanions can result in soluble as well as insoluble complexes; the monotetrazolium salts form soluble complexes and the ditetrazolium compounds form insoluble complexes. The insoluble complexes are stable at relatively low pH, and are disrupted during reduction to the formazan. Complex formation is decreased at high ratios of heparin to tetrazolium, and divalent cations, even at high concentration, do not precipitate mucopolysaccharides. It is concluded that stable ionic interactions with spatial charge separation are responsible for the cross linking of the mucopolysaccharides and the formaiton of large insoluble aggregates.

Nephrosis and papillary necrosis after pyelonephritis.

We present a case of nephrotic syndrome complicating acute pyelonephritis in a 45-year-old man. His first attack of acute bacterial pyelonephritis had two unusual features: transient nephrotic syndrome and chronic recurrent episodes of papillary necrosis. The former, which lasted for two weeks, was characterized by edema, excretion of 7.7 g of urinary protein per 24 hours and hypoproteinemia (1.8 g per 100 ml). A percutaneous renal biopsy two weeks after the height of the nephrotic state showed normal glomeruli by light and electron microscopy and immunohistologic studies. Interstitial changes were noted. Over two years the patient has passed approximately 50 fragments, characterized as necrotic tissue containing tubular structures. He has no evidence of diabetes mellitus, urinary-tract obstruction or ureteral reflux, analgesic abuse or atypical vasculitis. He is afebrile but has recurrent bacteriuria despite antibiotics. This case demonstrates that acute pyelonephritis must be added to the list of diseases causing the nephrotic state.