Light- and electron-microscopical study of a case of gold salt-induced hepatotoxicity.

A 56-yr-old woman with long-standing rheumatoid arthritis exhibited jaundice, pruritus and abdominal discomfort after 8 yr of periodic gold sodium thiomalate injections amounting to a cumulative dose in excess of 2.5 gm. Histopathological examination of the liver biopsy specimen showed submassive loss of parenchyma, collapse of reticulin and mixed cellular inflammatory infiltrates. Macrophages contained dark granules, which displayed the characteristics of aurosomes when examined by transmission electron microscopy and electron microprobe analysis. It is likely that hepatocellular injury occurred when the lysosomal storage capacity for gold was exceeded.

Chromium 51-ethylenediaminetetraacetate test: a useful test in the assessment of inflammatory bowel disease.

We evaluated the usefulness of urinary excretion values in assessing mucosal damage in inflammatory bowel disease after administration of chromium 51-labeled EDTA either orally or rectally. In the oral study, 19 controls, 18 patients with Crohn's disease, and 13 patients with ulcerative colitis were given 100 microCi 51Cr-EDTA by mouth. The amount of 51Cr-EDTA in a 24-hour urine collection was expressed as a percentage of the ingested dose. The patients with Crohn's disease of the small bowel excreted 6.3% +/- 4.3%, which was significantly (P less than 0.001) higher than the percentage in patients with ulcerative colitis (1.7% +/- 1.1%) and controls (1.4% +/- 0.6%). In the enema study, 19 patients with ulcerative colitis, two with Crohn's disease, two with radiation colitis, and four controls (spastic colitis, lactose intolerance) were given 100 microCi 51Cr-EDTA by retention enema. The patients with active colonic inflammation excreted 8.4% +/- 3.9% of the dose given by enema, which was significantly (P less than 0.01) higher than in other controls (1.9% +/- 0.91%) or patients with inactive colitis (2.2% +/- 1.9%). The 51Cr-EDTA excretion test is a safe, inexpensive test useful in evaluating patients with inflammatory bowel disease. It can be given orally to screen patients with abdominal complaints who are suspected of having Crohn's disease involving the small intestine, and when given by enema it provides additional objective assessment of idiopathic ulcerative colitis or proctitis.

Antibody-dependent cell-mediated cytotoxicity in serum samples from patients with ulcerative colitis. Relationship to disease activity and response to total colectomy.

A group of six medically treated patients with ulcerative colitis were followed for up to 30 months along with eight additional patients who underwent proctocolectomy. Patients were examined frequently, and serum samples were collected for antibody-dependent cell-mediated cytotoxicity studies. Clinically active disease was substantiated by history, physical examination, laboratory investigations, proctoscopy and, when feasible, by rectal and/or colonic biopsy specimens. During active clinical disease, serum samples from patients with ulcerative colitis showed antibody-dependent cell-mediated cytotoxicity of 16.5 +/- 1.6 percent (range 8.2 to 25.8 percent). During remission of the disease, serum samples from the same patients demonstrated a mean antibody-dependent cell-mediated cytotoxicity value of 5.9 +/- 1.3 percent (range 0.4 to 11.1 percent) (p less than 0.01). In the eight patients who underwent proctocolectomy, mean preoperative antibody-dependent cell-mediated cytotoxicity value was 19.5 +/- 2.3 percent (range 4.1 to 38.6 percent). One month after proctocolectomy, antibody-dependent cell-mediated cytotoxic activity decreased by 72 +/- 11 percent of the preoperative value (p less than 0.001). These findings reveal a positive correlation between the antibody-dependent cell-mediated cytotoxicity with RPMI-4788 and clinical activity of ulcerative colitis, and support the hypothesis that the antibody being studied has direct relation to the presence of the ulcerative colitis colon in situ.

Urinary ligandin and glutathione-S-transferase in gentamicin-induced nephrotoxicity in the rat.

1. Eight rats developed detectable glutathione-S-transferase activity in their urine after three daily injections of toxic doses of gentamicin. 2. Seven of the eight rats had immunodetectable ligandin in their urine at this time. 3. The level of enzyme activity correlated well with the degree of elevation of serum creatinine. 4. This confirms ligandinuria and urinary glutathione-S-transferase as markers of acute renal proximal tubular injury.

Immunocytochemical localization of hepatic legandin and Z protein utilizing frozen sections for light and electron microscopy.

Ligandin (glutathione-s-transferase) and Z protein are soluble hepatocellular proteins that are involved in the transfer of organic ions, including bilirubin and some hormones and carcinogens from the plasma to the liver. The intracellular distribution of ligandin and Z protein was studied by applying the peroxidase-antiperoxidase procedure of L. A. Sternberger (Immunocytochemistry, Prentice Hall Inc., 1974) to paraffin sections and free-floating 10-micrometers frozen sections that were processed for both light and electron microscopy. Ligandin and Z protein were localized to the cytosol of hepatocytes in association with smooth endoplasmic reticulum (SER), but no reaction product was present between cisternae of rough endoplasmic reticulum. Penetration of reagents was enhanced in 10-micrometers frozen sections and the preservation of subcellular structures was equivalent to thicker, unfrozen sections.

Ligandinuria: an indication of tubular cell necrosis.

Ligandinuria is a useful index of acute tubular injury. Ligandin probably enters the urine at the time of initial necrosis and should be looked for soon after the toxic or ischemic event. Periodic examination of perfusates for this substance might yield useful information about techniques for storage of cadaver kidneys.

Enzymatic evidence of renal tubular damage following renal angiography.

Ligandin, a glutathione (GSH) transferase, is a protein found in proximal tubular cells as well as in other tissues. It does not occur in the urine of normal subjects; however, its presence has been detected in the urine of some patients who have undergone renal angiography. This finding suggests renal tubular cell damage due to the procedure.