Monoclonal antibodies to a zinc-binding protein of rat Paneth cells.

Paneth cells are morphologically well characterized but their function has been not elucidated. Previously, we identified and purified a 90 KD zinc-binding protein (ZBPP-1) in rat intestine that was localized to Paneth cell granules, consistent with their high zinc content. To further elucidate the structure and function of ZBPP-1, we immunized Balb/c mice with purified ZBPP-1 and identified four independent monoclonal antibodies (MAb) producing MAb ZIP-1 (IgM), ZIP-2 (IgG1), ZIP-3 (IgM), and ZIP-4 (IgM).

A Paneth cell specific zinc-binding protein in the rat. Purification and immunohistochemical localization.

Background: Paneth cells are zinc-containing cells widely distributed in Lieberkühn's crypts of small intestine in many species, but their function has remained obscure. Our previous study showed that a single intravenous injection of diphenylthiocarbazone (dithizone), a zinc chelator, forms zinc-dithizonate complexes in the cytoplasm of Paneth cells to ensure rapid and selective killing of the cells.

Experimental Design: To verify the proteins that selectively deleted from intestinal mucosa after dithizone treatment, intestinal proteins from the rats with or without dithizone injection were compared in sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Selective killing of Paneth cells by intravenous administration of dithizone in rats.

Paneth cells are zinc-containing cells widely distributed in Lieberkühn's crypts of intestine in a variety of species. We found that rapid selective killing of Paneth cells took place after the intravenous (i.v.

Impairment of bone formation with aluminum and ferric nitrilotriacetate complexes.

The deleterious effects of aluminum(AL) and iron(Fe) on bone formation were studied in the presence of nitrilotriacetate (NTA) as a chelator. Both Al-NTA (1.0-1.

A case of biopsy-proven myocarditis progressing to autopsy-proven dilated cardiomyopathy.

A 22-year-old man presented with congestive heart failure following flulike symptoms. The diagnosis of acute myocarditis was confirmed by endomyocardial biopsy, which revealed mild infiltration of inflammatory cells. A favorable response to beta-adrenergic receptor blockade was seen, and the patient was discharged without symptoms.

Combined histochemical and biochemical analysis of sex hormone dependence of ferric nitrilotriacetate-induced renal lipid peroxidation in ddY mice.

Ferric nitrilotriacetate (Fe-NTA) induces renal proximal tubular necrosis, a consequence of lipid peroxidation, that finally leads to a high incidence of renal adenocarcinoma in rats and mice. Male animals are much more susceptible than female animals to both effects. Moreover, the distribution of the susceptible proximal tubules is different between male and female animals.

Sweet's syndrome associated with immunoblastic lymphadenopathy.

Sweet's syndrome arose in a 54-year-old Japanese man who had suffered from general malaise, episodic fever, and lymphadenopathy for ten months. Skin symptoms subsided rapidly, but he died three months later with a postmortem diagnosis of immunoblastic lymphadenopathy.

Induction of mesothelioma by intraperitoneal injections of ferric saccharate in male Wistar rats.

Iron appears to play a major role in catalysing free radical production, leading to lipid peroxidation and DNA damage. We, therefore, investigated the effect of colloidal iron deposited in the peritoneum. Wistar male rats were given either ferric saccharate, ferric saccharate and nitrilotriacetic acid (NTA), NTA or saline.

Thiobarbituric acid-reactive substance formation of rat kidney brush border membrane vesicles induced by ferric nitrilotriacetate.

An iron chelate, ferric nitrilotriacetate (Fe3+-NTA), is nephrotoxic and also carcinogenic to the kidney in experimental animals. Iron-promoted lipid peroxidation in the proximal tubules is thought to be responsible for the pathologic process. In the present study, iron-promoted lipid peroxidation, with thiobarbituric acid (TBA) formation as an indication, in the tubular surface was simulated in vitro using rat kidney brush border membrane vesicles and the results were compared with those using linoleate micelles and rat liver microsomal lipid liposomes.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. Report of an autopsy.

We present an autopsy report on a 14-year-old girl with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), placing emphasis on the mitochondrial enzymatic histochemistry of the 3 types skeletal muscle and cardiomyocytes. Generalized muscular atrophy, cardiac hypertrophy, cerebral cortical laminar necrosis, basal ganglia calcification and liver steatosis were observed. In the skeletal muscles, modified Gomori's trichrome staining demonstrated scattered ragged red fibers, and histochemical staining for mitochondrial enzymes showed intense positivity in the subsarcolemmal zones of some muscle fibers.

Oxygen reduction and lipid peroxidation by iron chelates with special reference to ferric nitrilotriacetate.

A certain iron chelate, ferric nitrilotriacetate (Fe3+-NTA) is nephrotoxic and also carcinogenic to the kidney in mice and rats, a distinguishing feature not shared by other iron chelates tested so far. Iron-promoted lipid peroxidation is thought to be responsible for the initial events. We examined its ability to initiate lipid peroxidation in vitro in comparison with that of other ferric chelates.

Cirrhosis of the liver induced by cupric nitrilotriacetate in Wistar rats. An experimental model of copper toxicosis.

Rats intraperitoneally injected with a daily dose of cupric nitrilotriacetate (Cu-NTA), which contained 4 to 7 mg of copper/kg body weight, showed submassive liver necrosis, hemolytic anemia, and acute renal tubular necrosis at the beginning of the experiment and intermittently after 4 weeks of injections. All rats that survived over 8 weeks exhibited liver fibrosis with portal-portal, portal-central, and central-central bridging. In all rats that survived over 16 weeks, micronodular cirrhosis of the liver or extensive liver fibrosis was observed.

Multicentric giant lymph node hyperplasia with ascites and double cancers, an autopsy case.

A 70-year-old man, diagnosed to have multicentric giant lymph node hyperplasia (MGLNH) of the plasma cell type by postmortem examination, had double cancers of the thyroid and kidney, as well as a large amount of ascites and persistent serositis. Serum immunoelectrophoresis showed monoclonal IgG (lambda). Using the paired immunofluorescent technique, monoclonal plasma cell proliferation was observed on the section of a lymph node.

Increased contraenvironmental-pressure cell division capability: a decisive force in metastasis and invasion of mouse lung adenocarcinoma cell lines.

The correlation between the growth of ML2, ML3 and ML4 cell lines in 1% agar cultures and their metastatic potential (mouse lung adenocarcinoma) was investigated. The growth ability in 1% agar cultures of ML2, ML3 and ML4 correlated far better with growth rates at lung metastatic sites than with the period required for the cells to reach the lungs following transplantation into the subcutaneum. Clones from 1% agar cultures of ML2, ML3 and ML4 show more conspicuous invasive and destructive growth than their monolayer counterparts in the muscle organ culture assay.

Pulmonary atypical carcinoid tumor with marked alphafetoprotein production and features of an adenocarcinoma differentiation.

A 67-year-old man presented with a pulmonary atypical carcinoid tumor with marked elevation of the serum alpha-fetoprotein (AFP) level to 181,000 ng/ml and no hepatic metastases. Immunohistochemistry revealed AFP-positive fine granules, sparsely distributed in some cells. The proportion of the concanavalin A nonbinding subfraction was 33.

Sex differences in ferric nitrilotriacetate-induced lipid peroxidation and nephrotoxicity in mice.

Since male A/J mice are much more susceptible to both acute and subacute nephrotoxicity and the carcinogenic effect of ferric nitrilotriacetate than female mice, sex differences in the lipid peroxidation level after ferric nitrilotriacetate use were examined. The effects of orchiectomy and testosterone were also investigated. Male and female A/J mice were given a single intraperitoneal injection of ferric nitrilotriacetate (3 mg of iron/kg of body weight) and then thiobarbituric acid reactivity was determined in the liver and the kidney.

Effect of dietary vitamin E on ferric nitrilotriacetate-induced nephrotoxicity in rats.

The effect of dietary vitamin E on renal tissue damage and lipid peroxidation was investigated following treatment with ferric nitrilotriacetate (Fe-NTA) in rats. Almost 100% renal proximal tubular necrosis was observed in the vitamin E-deficient rats following Fe-NTA treatment (5 mgFe/kg body wt, ip) as early as 12 hr. In the vitamin E-supplemented rats, no injury was observed in the proximal convoluted (cortical) tubules, although some injury was seen in the medullary outer stripe (mostly pars recta of the proximal tubules) 24 hr after Fe-NTA treatment.

A model for tumorigenicity and metastatic potential: growth in 1.0% agar cultures.

We developed a method to determine the amount of work performed by cells through cell division in 1.0% agar cultures. There was no correlation between the cloning efficiencies of 1.

Nephrotoxicity and its prevention by vitamin E in ferric nitrilotriacetate-promoted lipid peroxidation.

Iron and aluminum complexes of nitrilotriacetic acid cause severe nephrotoxicity in Wistar rats. In addition, a high incidence of renal cell carcinoma is seen in ferric nitrilotriacetate-treated animals. The present study was performed to see if lipid peroxidation is involved in ferric nitrilotriacetate toxicity.

Subacute nephrotoxicity and induction of renal cell carcinoma in mice treated with ferric nitrilotriacetate.

We investigated the induction of renal tumors by the ferric complex of nitrilotriacetic acid (Fe-NTA) in male and female A/J mice. Fifty-three male and 21 female mice received i.p.

An improved DAPI-DNA cytofluorometry by hypotonic cytolysis. Its application to tumor cell heterogeneity.

The effect of cell cytolysis on DAPI-DNA cytofluorometry was studied in order to eliminate nonspecific cytoplasmic hindrances in DAPI staining. A great improvement in the reproducibility of DNA determination was attained when cells were treated with hypotonic KCl (0.075 M) solution.

Nephrotoxicity of ferric nitrilotriacetate. An electron-microscopic and metabolic study.

Repeated intraperitoneal injections of ferric nitrilotriacetate (Fe-NTA) induce nephrotoxic features such as proximal tubular necrosis and renal failure, an unexpected phenomenon for a ferric compound. The mechanism of Fe-NTA toxicity was investigated by electron microscopy and respiration studies of renal cortical mitochondria in rats. Four hours after a single intraperitoneal injection of Fe-NTA, 5 mg iron/kg body wt, loss of microvilli, increased number of cytoplasmic vacuoles, electron-dense cytoplasmic deposits, mitochondrial swelling, karyorrhexis, and rupture of cytoplasmic membrane were observed in proximal tubular epithelia.

[Effect of PGF2 alpha on ovulation and collagenolytic activities in the rabbit treated by indomethacin].

To clarify a regulatory role of prostaglandins in collagenolytic enzyme activities of the follicular wall at ovulation, we studied whether the ovulation-blocking effect of indomethacin (IM) on hCG-stimulated rabbits could be reversed by an intravenous infusion of PGF2 alpha. The activities of BANA hydrolase and DNP peptidase were also measured by using synthetic substrates N-benzoyl-DL-arginine-2-naphthylamide HCl (BANA) and DNP-Pro-Gln-Gly-Ile-Ala-Gly-Gln-D-Arg-OH (DNP peptide), respectively, every hour during the specific preovulatory period. The ovulation-blocking effect of IM (4mg/kg) was reversed by an intravenous infusion of PGF2 alpha (1.

Nephrotoxicity and renal cell carcinoma after use of iron- and aluminum-nitrilotriacetate complexes in rats.

Wistar male rats were tested for nephrotoxicity and carcinogenicity after administration of ferric nitrilotriacetate [(NTA) CAS: 139-13-9] (Fe-NTA) [No. of rats (n) = 24] and Al-NTA (n = 24). The control rats were given AlCl3 (n = 10), NTA (n = 10), and saline (n = 10).