Species and sex differences of aflatoxin B1-induced glutathione S-transferase placental form in single hepatocytes.

Species and sex differences of aflatoxin B1 (AFB1)-induced glutathione S-transferase placental form (GST-P) positive single hepatocytes have been investigated 48 h after an intraperitoneal injection of AFB1 to young male and female Fischer rats (2 mg AFB1/kg body wt) and male Syrian golden hamsters (6 mg AFB1/kg body wt). The presence of GST-P positive hepatocytes was examined by the immunohistochemical method. Male rats formed three times as many AFB1-induced GST-P positive hepatocytes as females. Pretreatment of both male and female rats with an inhibitor of GSH synthesis, buthionine sulfoximine (BSO) (4 mmol/kg body wt), 2 h and 4 h before AFB1 injection increased AFB1-induced GST-P positive hepatocytes by about 120% above the controls. Male hamsters formed several-fold less AFB1-induced GST-P positive hepatocytes than male rats. Pretreatment with BSO did not increase AFB1-induced GST-P positive hepatocytes in hamsters even though it produced an increase in hepatic necrosis. It appears that GSH and GSH S-transferases play an important role in modulating hepatic AFB1-DNA binding and AFB1-induced GST-P positive hepatocytes in rats and hamsters.     

Suppressive effect of vitamin E on lipid peroxidation in halothane-administered guinea pig liver.

The effect of vitamin E on halothane-induced liver damage was studied in guinea pig halothane hepatitis. Twenty animals were divided into 3 groups, consisting of a control group, a halothane group and a vitamin E + halothane (H) group. The animals in the control group (n = 6) were allowed to inhale air only. The animals in the halothane group (n = 6) and the vitamin E + H group (n = 8) were allowed to inhale 1% halothane with air. Animals in the vitamin E + H group were additionally injected with 30 mg kg-1 of vitamin E 30 minutes prior to inhalation of halothane. Blood was aspirated from the heart immediately after sacrificing to measure the serum activity of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT). A microsomal suspension was prepared from the excised liver. Then the amount of thiobarbituric acid (TBA) reactive products in the microsomes were measured. The amount of tissue TBA-reactive products was increased by inhalation of halothane. The increase in the amount of TBA-reactive product was inhibited by the administration of vitamin E. The serum GPT activity was increased by halothane inhalation. Increased serum GOT and GPT activity were inhibited by the administration of vitamin E. These results demonstrated that vitamin E suppressed halothane-induced liver damage in the guinea pig by inhibiting lipid peroxidation.     

Inhibitory effect of anti-platelet prostaglandin on liver metastasis of hamster pancreatic cancer

Coagulation system and platelets play an important role in the stage of lodgement of tumor cells. We examined abilities of human and hamster pancreatic cancer cell lines to aggregate platelets in vitro, and investigated the effect of prostaglandin E1, I2, on artificial liver metastases of pancreatic cancer in Syrian golden hamster. Platelet aggregating activities were found in five out of six human pancreatic cancer cell line and thromboplastin likes activity in five cell lines. Diisopropanolnitrosamine induced hamster pancreatic cancer cells (HPK-1) were able to aggregate platelets both in vitro and in vivo and these activities were inhibited by prostaglandin I2. Hamster was inoculated intraportally with 1 X 10(6) HPK-1 cells. After two weeks autopsy of these hamsters revealed multiple metastatic nodules on liver surface. In this model we administered prostaglandin E1, I2 into the portal vein five minutes before cell inoculation. Number of liver surface nodules were significantly decreased to 33.1 + 7.0, 11.0 + 9.6 in hamster given 100g PGE1 PGI2 before cell inoculation, compared with control group of hamsters (62.0 + 6.6 PH9.3, 66.1 + 13.9 PH7.4). But administration of prostaglandin after cell injection was not effective. In all cases none of extrahepatic metastases were noted. Inhibitory action of PGE1 PGI2 on liver metastasis is suspected to be related to inhibition of platelet aggregation.     

Comparative in vitro and in vivo activity of rifabutin and rifampicin against Mycobacterium avium complex

In vitro antimicrobial activity of rifabutin and rifampicin against various mycobacteria, including the Mycobacterium avium complex, was evaluated by the agar dilution method, using 7H10 agar medium. The activity of rifabutin based on MIC50 and MIC90 was higher than that of rifampicin, against all the acid-fast organisms tested. Microbicidal activity of rifabutin against the M. avium complex phagocytosed in mouse peritoneal or alveolar macrophages was greater than that of rifampicin. Both rifabutin and rifampicin had therapeutic effects against murine infections induced by M. avium complex. Rifabutin was somewhat more effective than rifampicin in mice.     

Physiological significance of plasma free and conjugated dopamine in healthy volunteers--with special reference to sympathetic nerve activity

In order to elucidate the physiological significance of plasma dopamine, blood pressure, pulse rate (PR), plasma concentrations of free or conjugated dopamine (free or conjugated pDA), noradrenaline (pNA) and adrenaline (pAd) were measured in 9 healthy volunteers. Blood sampling for the measurements was performed at a basal condition maintaining a supine position for 60 minutes, after twenty minutes 60 degrees head-up tilt (tilt) and an intravenous infusion of 1000 ml 0.9% saline for 2 hours. Following tilt, mean values in diastolic and mean blood pressure, PR, pNA and pAd were significantly increased, while free, conjugated and total pDA were decreased. On the other hand, saline infusion yielded significant decreases in hematocrit, pNA, free, conjugated and total pDA, but blood pressure, PR and pAd remained at the same level. Free/conjugated pDA ratio did not change during tilt or saline infusion. The basal value of free, conjugated or total pDA did not significantly correlate with blood pressure, PR, pNA or pAd, respectively. Furthermore, no significant correlations between the changes in pDAs and hemodynamic parameters, pNA or pAd by tilt or saline infusion were observed. From these results, it was suggested that plasma free or conjugated dopamine in physiological conditions may not be released from sympathetic nerve endings or adrenomedullary glands. Further investigations are needed to clarify the physiological significance of plasma dopamine in humans.     

A case of mixed connective tissue disease successfully treated for hemophagocytic syndrome with intermittent intravenous injection of cyclophosphamide]

A 52 year-old woman noticed general fatigue, polyarthralgia, and muscle weakness of lower extremities in October 2001. In December, she felt difficulty in walking due to muscle weakness. In January 2002, she admitted another hospital because of dyspnea on exertion and edema of lower extremities. Laboratory test revealed leukocytopenia, the elevation of creatine kinase and positive anti-U1-RNP antibodies. Her chest computed tomography (CT) showed severe interstitial pneumonia. Cardiac echogram revealed that she had pericardial effusion and pulmonary hypertension. Then she was transferred to Keio University Hospital and she was diagnosed as having mixed connective tissue disease (MCTD) manifestating myositis, interstitial pneumonia, pulmonary hypertension and pericarditis. Prednisolone (PSL) 60mg daily following to methylprednisolone (mPSL) pulse therapy was begun and her symptoms were gradually improved. In middle of February, she complained of high fever over 39.0 degrees C. Bacterial culture tests were negative and laboratory data indicated pancytopenia and a high level of serum ferritin. Bone marrow aspiration revealed hemophagocytosis in bone marrow specimens and she was diagnosed as having hemophagocytic syndrome associated with MCTD. mPSL pulse therapy was not effective and intermittent cyclophosphamide pulse therapy (IV-CY) was performed resulting in improvement of the symptoms. This case suggested the effectiveness of IV-CY therapy in patients with corticosteroid-resistant HPS associated with connective tissue diseases.     

USEFULNESS OF EUS IN PORTAL HYPERTENSION WITH ESOPHAGEAL VARICES

We investigated the relationship between esophageal varices and the collaterals by endoscopy and endoscopic ultrasound (20 MHz ultrasonic miniprobe; UMP). Moreover, we investigated the correlation between the collaterals around the esophagus and recurrence of esophageal varices in patients with portal hypertension who had undergone EIS. The collaterals were divided into two groups: peri‐esophageal collateral veins (peri‐ECVs) and para‐esophageal collateral veins (para‐ECVs). These were scored as mild or severe according to the stage of development. According to endoscopy, the varix form was significantly larger in severe the peri‐ECVs group than in mild the peri‐ECVs group. The prevalence of perforating veins increased according to the varix form. With regard to variceal recurrence, in patients with variceal recurrences, UMP findings included a significantly higher incidence of severe peri‐ECVs, a significantly larger diameter of perforating veins compared with patients without recurrence. In conclusion, the presence of severe peri‐ECVs and large perforating veins in the esophageal wall strongly correlates with occurrence and recurrence of esophageal varices in patients with portal hypertension. An understanding of these UMP abnormalities on the basis of hemodynamics around the esophagus is thought to be important for management of esophageal varices in patients with portal hypertension.     

Human parvovirus-induced transient anemia and leukopenia after delivery]

A 30-year-old female at 27 weeks' gestation, was hospitalized on September 24 1990 because of the premature rupture of the amniotic sac. She underwent Caesarean section on the same day with 700 ml blood loss, but no blood transfusion was required. For several days after the operation, her hemoglobin level remained 7.8 g/dl and did not increase significantly in spite of parenteral iron therapy. On the 9th postoperative day, chills and pyrexia developed with leukopenia. Bone-marrow aspiration revealed severe erythroblastopenia with giant proerythroblasts, suggesting recent HPV infection, which was confirmed by the presence of anti-HPV IgM and HPV antigen by ELISA. The hemoglobin level gradually decreased to 6.0 g/dl by the 21st day, then began to increase rapidly. The serum of acute-phase containing HPV antigens inhibited BFU-E and CFU-E but not CFU-GM. The serum of convalescent-phase inhibited neither erythroid colony growth nor myeloid colony growth. These results indicate that the inhibitory effect of HPV in colony assay is highly specific for erythropoiesis and that HPV play a role in transient cessation of erythropoiesis. The reason, however, for leukopenia in HPV infection remained unclear. This case shows that HPV infection may induce severe hematological disorders even in normal person under erythropoietic stress.     

Discrepancy of xenon concentrations between end-tidal and blood collection methods in xenon-enhanced computed tomographic measurement of cerebral blood flow

Summary Using xenon-enhanced computed tomography for the study of cerebral blood flow, simultaneous measurements of end-tidal and arterial blood xenon concentrations using the blood collection method were performed to investigate the validity of substituting the end-tidal for the arterial blood xenon concentration. Simultaneous measurement by both methods was performed 68 times in 27 patients. There was no statistical correlation between the arterial blood accumulation rate constant obtained by arterial blood and end-tidal samples, nor between the arterial blood saturation value obtained by the two methods, even when correction was made for age. In brain tissue, all parameters calculated using the end-tidal concentration were lower than those using arterial blood. We therefore suggest that cerebral blood flow values calculated using end-tidal xenon concentration are useful only for qualitative cerebral blood flow mapping, and not applicable to absolute values of cerebral blood flow.