Irving Seidman

Toxicity of enzymically-oxidized low-density lipoprotein.

Intravenous injection of cholesterol oxidase into hyperlipidemic rabbits in which aortic atheromatous lesions have been induced by dietary means is lethal within hours, whereas injection of the same enzyme into normal rabbits has no visible adverse effect. The lethal effect of the enzyme is explicable by the finding that injection of cholesterol-oxidase treated low-density lipoprotein kills normal rabbits, in contrast to untreated low-density lipoprotein which does not. Enzymically oxidized low-density lipoprotein was also found to be cytotoxic for two human cell lines and for cultured bovine aortic endothelial cells. We suggest that in vivo enzymic conversion of low-density lipoprotein cholesterol to low-density lipoprotein cholestenone may possibly play a role in the initiation of atheromatous lesions in humans.

Case Report Irreversible pulmonary toxicity after single course of BCNU

Irreversible pulmonary interstitial fibrosis developed 36 days after a single course of BCNU (total, 400 mg) in a patient with a malignant brain tumor. The case is unique in that irreversible changes developed shortly after a single course of BCNU whereas heretofore such permanent changes have been associated only with multiple courses of the drug (2,000-4,000 mg). This suggests that individual differences in the local sensitivity of lung tissue may be as important as the dose of the drug in determining whether irreversible fibrosis will develop.

Eyelid deformities caused by the injection of silicone fluid

Summary Medical grade dimethylpolysiloxane (silicone) fluid has proved satisfactory as an injectable subcutaneous tissue prosthesis in the treatment of certain deformities such as hemifacial atrophy. The injection of this material beneath the eyelid skin can result in the formation of palpebral bags because of localisation of the tissue reaction and the thinness of the eyelid skin. Surgical excision of the localised silicone mass is indicated in some patients, although total excision is usually not possible. Patients with such eyelid lesions are presented.

Depression of Tryptophan Pyrrolase Induction in Regenerating Rat Liver.

Summary The induction of tryptophan pyrrolase by hydrocortisone has been studied in the regenerating rat liver. An initial depression of response, presumably related to the operative procedure, was observed in both sham operated and partially hepatectomized animals. In partially hepatectomized animals, a second depression was observed during that period in which DNA synthesis has been shown to occur. It has been suggested that alterations in enzyme control mechanisms, such as the failure of tryptophan pyrrolase induction by cortisone in minimum deviation hepatomas, may be a fundamental biochemical alteration in tumors. This study shows that a depressed response to hormonal enzyme induction is found in non-neoplastic hepatic cells preparing to divide.

Hydrocortisone Induction of Tyrosine Transaminase in Regenerating Rat Liver

THE “minimal deviation” hepatomas—well differentiated rat hepatocellular carcinomas—demonstrate many abnormal enzyme regulatory mechanisms1. It has been suggested that these alterations are critical in neoplastic transformation2. The corticosteroid induction of the hepatic enzymes tryptophan pyrrolase (TP) and tyrosine transaminase (TT) has been extensively studied in these tumours1. Administration of corticosteroid causes a considerable increase in the activities of TP and TT in the normal adult rat liver within 4–5 h (refs. 3 and 4). In hepatomas, however, there is little or no increase in TP activity after administration of corticosteroid, and baseline enzyme activity is usually depressed1.

An experimental evaluation of skin graft preservation with silicone fluid

Abstract Short-term preservation of rat skin allografts in dimethylpolysiloxane fluid at different temperatures has been experimentally evaluated and described. Since storage of excised skin in silicone at 12 ° allows graft survival, this suggests to the surgeon the possibility of a very simple and rapid short-term source of skin. Despite the fact that methods are available which permit the preservation of skin for longer periods of time, the silicone technique appears to be much less complicated and exacting. Although the attempts to preserve skin in a freezer (−9.5 °) have failed, further information is needed to evaluate the interrelationship between the time-temperature and the biological effects of skin preserved in silicone fluid.

Rapid Induction of Thymic Lymphomas by Isopropyl Methanesulfonate: A Preliminary Report

Abstract The direct-acting SN1 alkylating agent isopropyl methanesulfonate (IMS) was carcinogenic by subcutaneous injection in female Hsd:(ICR)BR mice, causing thymic lymphoid neoplasms within 7 months in at least 20 of 32 treated mice. No such neoplasms were observed in mice treated with the direct-acting SN2 methyl homolog, methyl methanesulfonate (MMS). Both the IMS-treated mice and the MMS-treated mice initially received 20 μmole of the respective compounds by sc injection once weekly; however, because of toxic effects the dose of IMS was reduced to 10 μmole per injection on the 63rd day and further reduced to 5 μmole per injection on the 120th day, after which this dose was maintained until the 202nd day when the last surviving IMS-treated mouse became moribund and was sacrificed. In 2 of the MMS-treated mice, 93% of which were alive at 288 days, tumors were observed at the site of injection, one being a papilloma and the other a subcutaneous sarcoma. IMS has not previously been implicated as a carcinogen, to our knowledge. Its induction of thymic lymphomas may conceivably be related to its ability to alklyate exocyclic oxygen atoms in the DNA of hemopoietic cells.

Anaerobic Cell Function: Effect of Fasting on Cation Transport in Rat Liver Slices

Summary Rat liver slices from fed or fasted animals do not have the ability to conduct cation transport when subjected to anoxia. However, anoxic cation transport can be stimulated in liver slices of fed animals when slices are preincubated under O2. In addition, anoxic cation transport can be stimulated by incubation of slices in pyruvate, oxalacetate, or phosphoenolpyruvate. These conditions did not stimulate anoxic cation transport in liver of fasted animals. All attempts at metabolite reconstitution also failed to elicit anoxic cation transport in liver of fasted animals.

MMTV/N-ras Transgenic Mice as a Model for Altered Capacitation Male Sterility and Tumorigenesis

Infertility is generally defined as a failure to conceive following one year of unprotected intercourse; it affects about 10% to 15% of couples attempting a pregnancy for the first time (Romeny et al., 1975). Abnormalities in the male partner contribute to infertility in about 40% of these couples (Speroff et al., 1983).

Gastric duplication cyst: electron microscopic and immunohistochemical study.

The lining of a gastric duplication cyst was examined ultrastructurally and immunohistochemically. The cyst lining displayed the range of differentiation seen in normal fundic mucosa.