The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachloride.

Allyl sulfides, e.g., diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), are principal constituents of garlic oil. In the present study, we investigated the in vivo effect of these sulfides on the phase I and phase II drug-metabolizing enzymes, and elucidated their structure-function relationship. A highly purified form of each sulfide (more than 99% purity) was administered i.p. as a bolus to rats at a concentration of 10 or 100 micromol/kg body weight for 14 consecutive days. As to the phase I enzymes, DAS (100 micromol/kg) slightly but significantly increased cytochrome P-450 (CYP) 2E1 activity (1.6-fold vs. control), whereas DADS and DATS did not affect it or the hepatic total CYP level or CYP1A1/2 activity. With respect to the phase II enzymes, DATS (10 micromol/kg) and DADS at a 10-fold higher dose (100 micromol/kg) significantly increased the activities of glutathione S-transferase, quinone reductase, and antioxidative enzyme glutathione peroxidase; whereas DAS did not. In the carbon tetrachloride (CCl4)-induced acute liver injury model of rats, either DATS (10 micromol/kg) or DADS (100 micromol/kg) significantly reduced the injury caused by the induction of phase II enzymes with CCl4. In conclusion, the sulfides affected both phase I and phase II enzymes, the former being stimulated by the monosulfide only and the latter, strongly by the trisulfide and weakly by the disulfide. Therefore, the polysulfide DATS may be one of the important factors in garlic oil that protects our body against the injury caused by radical molecules encountered in daily life.     

Pulmonary inflammatory pseudotumor with rapid growth and serum carcinoembryonic antigen elevation

Inflammatory pseudotumors consist of chronic inflammatory cells, predominantly plasma cells. We report a rare case of pulmonary inflammatory pseudotumor associated with rapid growth and elevated serum carcinoembryonic antigen (CEA). A 75-year-old man referred for bloody sputum was found in chest computed tomography (CT) to have a round circumscribed tumor with a cavity located in the periphery of the right lower pulmonary lobe. Cytological examination of a biopsy specimen obtained by CT-guided transthoracic fine needle aspiration showed no malignancy. Two months later, the tumor had noticeably grown, accompanied by a notable rise in serum CEA. We conducted right lower pulmonary lobectomy with regional lymph node dissection, since malignancy could not be ruled out by frozen-section examination. Histological examination of the resected specimen showed an inflammatory pseudotumor with CEA production.     

A case of cystadenocarcinoma developing from an ovary autografted to the abdominal wall

A 73-year-old woman developed an abdominal tumor. We performed tumor resection. The tumor, located between the fascia and peritoneum, was removed completely. The histological finding was cystadenocarcinoma. Thirty-eight years earlier she had undergone total hysterectomy and bilateral oophorectomy because of abnormal genital bleeding. At that time, her own ovary had been transplanted to the abdominal wall. We diagnosed this tumor as having developed from the autografted ovary. The complication of ovarian autografting is cystic degeneration. This complication is rare in Japan. Moreover, malignant change is extremely unusual in ovarian autografting.     

Urine plasmin-like substances as an index of kidney allograft rejections.

Using solid state radioimmunoassays developed by the first author, changes in the urine level of plasmin-like substances (PLS) and fibrin degradation products (FDP) before and after human kidney transplantation were determined in 49 transplant patients. Averages of urine PLS and FDP in a normal population of 51 persons were 0.13+/-0.10 (SD) and 0.14+/-0.07 microng/ml, respectively. In all transplant patients there was an initial rise of both PLS and FDP in urine immediately after transplantation. This elevation peaked on days 4 and 5 and the PLS and FDP levels returned to normal range within 2 weeks in patients without evidence of rejeciton. A secondary rise of urine PLS was detected before or with a rise in serum creatinine in all of the patients experiencing rejections. Of 11 patients who showed a rejection episode within 2 weeks of transplantation, the secondary rise of urine PLS was detectable in 55% of the patients slightly before the serum creatinine level changes; of 6 patients with a rejection episode more than 2 weeks after transplantation, 100% showed a secondary PLS rise 6.7+/-2.3 (SE) days before the serum creatinine increased. The appearance of the secondary rise of urine FDP in the rejecting recipients was slightly later than the rise of PLS. Serial determination of urine PLS levels following human kidney transplantation appears to be an early index of rejections which occurs more than 2 weeks after transplantation, although the clinical usefulness of this measurement is probably limited.     

Immunochemical and immunohistological analyses of tumor-associated antigens defined by murine monoclonal antibodies against human pancreatic carcinoma cells

Two murine monoclonal antibodies, SK-930 (isotype IgG2a) and SK-117 (isotype IgG1), were produced from spleen cells of mice immunized against human pancreatic carcinoma cell lines, MIA-PaCa 2 and Panc-1. With the use of the avidin-biotin-immunoperoxidase technique, the SK-930 and SK-117 antibodies detected an antigen found in 24 and 23 formalin-fixed tissue sections, respectively, of tumors obtained from 30 different patients with pancreatic carcinoma. Reactivity was also frequently found with tumors of the gallbladder, bile duct, stomach, colon and esophagus, while a large panel of normal human tissues, including normal pancreatic tissues, displayed little reactivity. These observations suggest that SK-930 and SK-117 are of value in identifying tumor-associated antigen (TAA) expressed in pancreatic carcinoma and other carcinomas of the digestive system. SK-930 antibody immunoprecipitated a 134 kilodalton molecule from extracts of 125I- or [35S]methionine- or [3H]glucosamine-labeled tumor cells. The SK-117-defined antigen corresponds to 152/137 kilodalton molecules. Moreover, cytofluorometric analyses showed that cells treated with periodic acid exhibited greatly decreased reactivity to the two antibodies, but cells treated with neuraminidase, trypsin or pronase showed unchanged reactivity. The findings suggest that the epitopes of the novel TAA expressed on pancreatic carcinoma cells are carbohydrate moieties.     

Accumulation of Tc-99m MIBI in breast lymphoma: Comparison with Ga-67 citrate

We report 2 cases of malignant lymphoma of the breast which were clearly shown on total body imaging as well as on SPECT with Ga-67 and Tc-99m MIBI. Tumor accumulation of Ga-67 was seen in all cases including a recurrent tumor. Ga-67 scintigraphy is useful for follow up in detecting relapse, as well as in predicting responses to therapy. Tc-99m MIBI was found to accumulate in the malignant lymphoma of the breast, and especially SPECT images of breast lesions provided better contrast than planar images, and Tc-99m MIBI SPECT could diagnose localization of the tumor because there was no uptake by the breast. But the Tc-99m MIBI accumulation of the tumor was lower than Ga-67.     

Biochemical investigation of a Brazilian patient with a defect in mitochondrial acetoacetyl-coenzyme-A thiolase

A case report of 3-ketothiolase deficiency due to a defect of mitochondrial acetoacetyl-CoA thiolase protein in a Brazilian boy and its biochemical investigation is presented. The child had moderate generalized hypotonia, EEG alterations and crises of metabolic acidosis following infections. Hypotonia and EEG abnormalities disappeared with a low protein diet, and physical and mental development are normal. Urinary organic acid excretion was typical of 3-ketothiolase deficiency, showing consistently high levels of 2-methyl-3-hydroxybutyric acid and tiglylglycine. Activation of acetoacetyl-CoA thiolase activity by potassium (K) ion in cultured fibroblasts was not observed, demonstrating the lack of activity of mitochondrial acetoacetyl-CoA thiolase. In addition, the signal for the mitochondrial acetoacetyl-CoA thiolase protein was undetectable in the immunoblot analysis. In the pulse-chase experiments, the signal for mitochondrial acetoacetyl-CoA thiolase was detected after a 1-h pulse but not after a 24-h chase. These results indicate that the deficiency was caused by an unstable mitochondrial acetoacetyl-CoA thiolase protein.