Liver selenium and testis phospholipid hydroperoxide glutathione peroxidase are associated with growth during selenium repletion of second-generation Se-deficient male rats.

We have previously shown that changes in glutathione peroxidase-1 (GPX1; H2O2:oxidoreductase, EC 1.11.1.9), plasma thyroid hormone and glutathione-S-transferase were not associated with changes in growth observed in second-generation (F2) severely Se-deficient rats; we also found that liver phospholipid hydroperoxide glutathione peroxidase (GPX4; EC 1.11.1.12) activity falls in first-generation (F1) Se-deficient rats to 41% of levels in Se-adequate rats. The purposes of this study were to determine the effect of F2 Se deficiency on GPX4 and to detect early changes in Se parameters associated with growth after single, small Se injections. Se-deficient male F2 weanling rats were randomly divided into two groups and fed a Se-deficient crystalline amino acid (0.003 microg Se/g diet; -Se) diet or that diet supplemented for 14 d with 0.2 microg Se/g diet (+Se) as Na2SeO3. Growth of -Se rats was 55% of the rate of +Se rats. Liver Se, GPX1 activity, GPX4 activity and testis GPX4 activity in -Se rats at 14 d were 1, 2, 23 and 13%, respectively, of levels in +Se rats. In a series of experiments, additional F2 male weanling rats were fed the -Se diet for 14 d and then were given an intraperitoneal single saline injection of 0, 1 or 5 microg Se/100 g body weight (BW) as Na2SeO3 and killed 1 or 7 d later. Rats injected with 1 or 5 microg Se/100 g BW grew 36 or 48%, respectively, above the rate of saline-injected rats. Liver Se concentration increased 367% and testis GPX4 activity doubled in rats 1 d after injection of 1 microg Se/100 g BW compared with saline-injected rats; these parameters were further elevated with 5 microg Se/100 g BW injections. Increases in liver Se and testis GPX4 activity were the parameters best associated with improved growth after Se injection, but the molecular role for Se in growth remains unclear.

Growth and plasma triiodothyronine concentrations are modified by selenium deficiency and repletion in second-generation selenium-deficient rats.

Classical glutathione peroxidase (GPX) is a useful Se-dependent parameter for determining Se status, but loss of GPX activity alone cannot explain the full effects of Se deficiency. The recent identification of type I thyroxine 5'-deiodinase as a Se-dependent enzyme provides a new potentially critical role for Se. To develop a model of impaired growth due to Se deficiency, second generation deficient weanling rats were fed a Se-deficient amino acid diet with adequate vitamin E and methionine. Initial growth rates of deficient males and females were 53 and 63%, respectively, of rats fed 0.1 micrograms Se/g diet. In short-term experiments with deficient males, liver Se and GPX activity were reduced 99%, liver glutathione-s-transferase activity was increased 114%, plasma thyroxine concentrations were increased 67%, plasma triiodothyronine was decreased 23% and the plasma triiodothyronine:thyroxine ratio was decreased 55%, compared with rats fed 0.2 micrograms Se/g diet. When deficient rats were injected on d 14 with 0, 1, 5 or 10 micrograms Se/100 g, rats grew 4.45, 7.62, 7.17 and 9.05 g/d, respectively, over the next 7 d. Injection with 10 micrograms Se/100 g restored plasma thyroxine and triiodothyronine concentrations 7 d later. Rats injected with 1 microgram Se/100 g rat had significantly altered plasma thyroxine and triiodothyronine concentrations 1 but not 7 d after injection. Infusion of Se-deficient rats with 438 ng triiodothyronine/d for 7 d restored plasma triiodothyronine concentrations but did not increase growth rate compared with rats infused with saline. This model produced a significant growth depression that was significantly reversed by as little as 1 microgram Se/100 g rat, but not by triiodothyronine infusion, suggesting that other Se-dependent roles in addition to 5'-deiodinase and GPX are necessary for adequate growth.

Deantigenation of human type B erythrocytes with Glycine max alpha-D-galactosidase.

Conversion of erythrocyte membrane B antigen to H antigen produces blood type O which is universally transfusable. If efficient large-scale production of enzymatically converted red blood cells is to be achieved, then optimal conditions for deantigenation must be determined. Cell suspension assays were used to study the blood group B activity of Glycine max (soybean) alpha-D-galactosidase on native human erythrocytes. The enzyme readily hydrolyzed the terminal alpha-D-galactosyl residue of the B antigen, converting it to H antigen. Optimal conditions for the enzymatic conversion of red cells with the Glycine enzyme are described. Normal cell morphology and function were maintained under optimal conditions.

Multiple hamartoma syndrome (Cowden's disease) associated with renal cell carcinoma and primary neuroendocrine carcinoma of the skin (Merkel cell carcinoma).

A case of multiple hamartoma syndrome (Cowden's disease) associated with renal cell adenocarcinoma and primary neuroendocrine carcinoma of the skin is described. Neither of these neoplasms has been documented previously in association with this genodermatosis. A search for epidermal growth factor receptor (c-erb-B protooncogene) gene abnormalities in the kidney, liver, and thyroid, as well as in tissue of the primary neuroendocrine carcinoma, was negative. Serum obtained from the patient before his death contained elevated levels of both chromogranin A (2641 ng/mL; normal level, less than 20 ng/mL) and calcitonin (517 pg/mL; normal level, less than 200 pg/mL), suggesting that the patient's principal tumor was neuroendocrine in origin.

Systemic mastocytosis associated with membranous nephropathy and peripheral neuropathy.

A report of the occurrence of membranous nephropathy and peripheral neuropathy in a patient with systemic mastocytosis is presented. Previous reviews of patients with systemic mastocytosis have not noted this association. During cyclical therapy with prednisone and chlorambucil in this case, nephrotic-range proteinuria remitted. Peripheral neuropathy resolved 10 months after discontinuation of therapy. Pathophysiological mechanisms resulting in this clinical presentation may be immunologically mediated.

Central pontine myelinolysis: a complication of hyponatremia or of therapeutic intervention?

We report four cases of central pontine myelinolysis (CPM) that illustrate important features of the disorder. The condition is described mainly in the neurological literature and, to our knowledge, is not discussed in the forensic science journals. This disorder must be recognized and understood by the forensic science expert who addresses issues of liability. In cases of multiple motor deficits and death with a history of hyponatremia, CPM must be included in the differential diagnosis. Careful examination of the pons and adjoining structures must be performed. Myelin stains are advisable. The association of CPM with major illnesses, hyponatremia and the correction of hyponatremia by intravenous saline infusions is discussed.

Homicide by insulin administration.

This report describes a case of homicide by insulin administration and a study of the effects of storage conditions on insulin in serum. The study revealed insulin to be remarkably stable at refrigerator temperatures. Therefore, for forensic science purposes, insulin immunoassay data are interpretable even when serum is not stored by the standard laboratory method of freezing.

Squamous cell carcinoma of the uterine cervix subsequent to amebiasis.

We studied the development of a well-differentiated squamous cell carcinoma of the uterine cervix five years after cervical infection with Entamoeba histolytica by documenting the findings of specimens obtained by repeated biopsies in a 69-year-old woman. To our knowledge, this is the first report of a malignant neoplasm of the uterine cervix subsequent to amebiasis. Amebiasis superimposed on malignant neoplasms of the female genital tract has been reported before. We raise the question of a possible causal relationship between amebiasis and subsequent squamous cell carcinomas of the cervix.

Neoplasms arising in Paget's disease of bone: a study of 82 cases.

Eighty-two cases of neoplasms arising in Paget's disease of bone from the Mid-America Bone Tumor Registry, accessioned between 1958 and 1983, were reviewed. There were 77 osteosarcomas, 3 fibrosarcomas, 1 chondrosarcoma, and 1 giant cell tumor. The male/female ratio was 2:1. The age distribution was 18%, 29%, 36%, and 17% for the groups less than 51 years, 51-60 years, 61-70 years, and greater than 70 years, respectively. The femur was involved by tumor in 22%; the humerus in 21%; the pelvis in 21%; the calvarium in 12%; the tibia in 10%; and other bones in 15% of the cases. There were 48% survivors after 1 year; 17% after two; and 5% after three and five years; two additional patients with tumor lived for more than seven and 11 years. Radiographs available for simultaneous study in 43 cases revealed predominant tumor patterns that were mixed in 69%, osteoblastic in 21%, and osteolytic in 10%. Other radiographic data and the clinical and histopathologic data are in agreement with five earlier major studies. While the prognosis of neoplasms arising in Paget's disease generally is not good, a small fraction of long-term survivors after aggressive therapy makes this complication a challenge for timely radiographic diagnosis and histopathologic confirmation.

Ciliated adenocarcinoma of the endometrium.

Two cases of ciliated endometrial adenocarcinoma which came to attention in less than one year are described. This entity deserves emphasis, as its ciliation may distract from its histological malignant features. Association of cilia with atypical nuclear features in the same cell is the diagnostic characteristic which distinguishes it from non-ciliated adenocarcinoma overrunning non-malignant ciliated endometrium. The ultrastructural detail of the cilia of malignant cells does not differ from that of non-malignant endometrial glandular epithelium. Our cases raise the question of a possible association of estrogenic effect with ciliated endometrial adenocarcinoma.

Serum creatine kinase in marathon runners.

Serum creatine phosphokinase (CK) and CK-MB activity were determined in 21 trained runners participating in a marathon race (42.2 km). Enzyme activities immediately after the race increased two to three times compared with activities before the race. The greatest increases were found in the slowest runners, suggesting greater skeletal muscular trauma in the least trained or fit. As these are likely to include the older athletes who are also more likely to suffer acute myocardial injury during strenuous exercise, our findings assume special import in the interpretation of increased CK and CK-MB serum activities of older athletes.

Acetaminophen overdose with fetal demise.

A case of fetal demise and maternal recovery after acetaminophen overdose is presented, to our knowledge the first reported. Fetal liver and maternal serum concentrations indicate overdose to be the cause of fetal death. Maternal disseminated intravascular coagulation (DIC) may have been related to maternal acetaminophen-induced liver disease alone or to a combination of liver disease and the presence of a dead fetus.

Pentazocine-induced agranulocytosis.

A 46-year-old man with pentazocine-induced agranulocytosis is described. In previously reported cases of a complete absence of mature neutrophils in the peripheral blood and bone marrow the patients had undergone marrow-depressing treatment with radiation and antineoplastic drugs. This case is unique in that the patient had complete agranulocytosis without predisposing factors.