Biliary excretion of bile acids and organic anions in zone 1- and zone 3-injured rats.

AIMS: Hepatocytes in zone 1 of the hepatic lobule play a role in the uptake and biliary excretion of bile acids and organic anions under physiological conditions, and those in zone 3 may play a role only with a high-dose load. To further elucidate the role of hepatic zonation on the handling of bile acids and organic anions, biliary excretion of these compounds was studied in zone 1- and zone 3-injured rats. METHODS: Biliary excretion of bile acids and organic anions was studied in zone 1- and zone 3-injured rats, caused by allyl alcohol and bromobenzene, respectively. RESULTS: Biliary excretion of a tracer dose of taurocholate was unchanged in the injury in both zones, but that of leukotriene C4 was decreased in zone 1 injury. The excretory maximum of taurocholate was decreased with zone 1 and the zone 3 injuries. Biliary excretion of deoxycholate metabolites was decreased in zone 3 injury, although the profile of metabolites in the bile was unchanged. Sulfobromophthalein excretion was decreased in zone 1 injury, but unchanged in zone 3 injury. CONCLUSIONS: These findings indicate that zone 1 is very important for biliary excretion of both organic anions and bile acids. In contrast, zone 3 is considered not to have a role in biliary excretion of organic anions, but to play a role in the excretion of bile acids.

Effect of tauro-alpha-muricholate and tauro-beta-muricholate on oestradiol-17 beta-glucuronide-induced cholestasis in rats.

The effect of tauro-beta-muricholate (beta MC-tau) and tauro-alpha-muricholate (alpha MC-tau) on oestradiol-17 beta-glucuronide (E217G)-induced cholestasis was compared with that of tauroursodeoxycholate (UDC-tau) in rats. Like UDC-tau, alpha MC-tau and beta MC-tau infused at the rate of 0.2 mumol/min per 100 g bodyweight (BW) completely inhibited the cholestasis induced by E217G infused at the rate of 0.06 mumol/min per 100 g BW for 20 min. These findings indicate that beta MC-tau and alpha MC-tau are useful in protecting against various types of experimental cholestasis, as well as against bile acid-induced cholestasis.

[Aspergillus lumbar discitis in a patient with acute lymphoblastic leukemia following induction therapy].

A 47-year-old female was admitted in October 1988 because of anemia and lymphoblastic cells in peripheral blood. A bone marrow aspirate was hypercellular with 93.9% lymphoblasts negative for peroxidase staining. The case was diagnosed as ALL (L2), and treated with JALSG ALL-87 regimen. She developed spiky fever and endotoxin shock due to bacteremia caused by pseudomonas aeruginosa, then was treated with several antibiotics. With the recovery of leukocytes, the chest X-ray showed an infiltrative shadow and a cavity forming lung abscess resembling aspergilloma in her left lung. The cavity improved of transbronchial infusion following amphotericin B (AMPH-B). Although she achieved complete remission, she felt severe lumbago accompanied by a marked erosion of the vertebral body with disc space narrowing on her X-ray. Then she underwent surgery to remove a disc abscess, and 1 colony of the aspergillus species was cultured from the specimen. She was treated with intravenous AMPH-B, and post remission therapies were performed under the injection of anti-fungal agents. No remarkable symptoms of complications were recognized during the chemotherapy. AMPH-B is useful and safe for the management of aspergillus discitis.

[A "retinoic acid syndrome" observed in two cases of acute promyelocytic leukemia].

Two cases of acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) developed fever, dyspnea and chest pain. A chest roentgenogram showed bilateral pleural effusion (case 1) and bilateral interstitial infiltration (case 2). The first case was a 50-year-old female in her first relapse, who was initially diagnosed as having pleuritis tuberculosa and was treated with anti-tuberculotic agents. Her symptoms continued for 44 days and complete remission was achieved 53 days after commencing ATRA therapy. The second case was a previously untreated 46-year-old male. His case had been diagnosed as adult respiratory distress syndrome and he had been treated with prednisolone. His symptoms rapidly improved and complete remission was achieved 38 days after the ATRA therapy. This was the first report of patients in Japan considered to have developed "retinoic acid syndrome (RAS)". In our five APL cases treated with ATRA, the syndrome was not always accompanied by peripheral blood leukocytosis even though the two cases with RAS showed higher leukocyte counts than the other two cases without RAS and also had DIC. We should pay attention to the severe respiratory symptoms that develop in APL patients after ATRA treatment and immediate steroid therapy is required for such patients.

Interstitial pneumonitis possibly due to mitoxantrone.

A 41-year-old patient with chronic myelogenous leukemia in the accelerated phase was treated with mitoxantrone. She developed pyrexia 7 days after receiving the third administration of mitoxantrone. After 3 more days, she experienced dry cough and dyspnea. Bilateral fine crackles were audible, but no signs of heart failure were found. A chest X-ray film revealed diffuse reticulogranular infiltrates bilaterally. An increase in the prednisolone dosage led to an improvement. Specimens of the bronchoalveolar lavage revealed an increase in CD4-/CD8- lymphocytes. The peripheral lymphocytes also expressed neither CD4 nor CD8. Specimens of a transbronchial lung biopsy disclosed thickening of the alveolar wall with infiltration of lymphoid cells.

Myeloblastoma formation in acute myeloid leukemia.

The cell surface markers on the leukemic cells of 76 patients with adult acute myeloid leukemia (AML) have been analyzed by indirect immunofluorescence, and the presence of CD56+ leukemic cells was detected in ten of these patients. Four of these 10 CD56+ AML patients developed extramedullary myeloblastomas and in two of them an intracranial myeloblastoma. In contrast, in the remaining 66 CD56- AML patients, only one patient developed a myeloblastoma formation of the subcutaneous. It may be that the CD56 antigen which is an isoform of the neural cell adhesion molecule (NCAM), expressed on neurons, satellite cells of skeletal muscle cells, and on stromal cells, binds these tissues by a homophilic mechanism. CD56+ leukemic cells are capable of invading and of surviving in extramedullary tissues, where they proliferate and develop into a myeloblastoma. Because of this possibility, CD56+ AML patients should be carefully monitored for signs of myeloblastoma formation.

The monocyte tumor necrosis factor-alpha production in patients with acute leukemia in complete remission.

Tumor necrosis factor-alpha (TNF-alpha) production by unstimulated and lipopolysaccharide (LPS)-stimulated peripheral monocytes has been studied in 17 acute myeloid leukemia (AML) patients, 54 AML patients in complete remission (AML-CR), 9 acute lymphoblastic leukemia (ALL) patients and 13 ALL patients in complete remission (ALL-CR). TNF-alpha production by the unstimulated monocytes in ALL patients (n = 6, mean: 6.6 +/- 4.9 u/ml) was higher than that of normal controls (n = 13, 0.9 +/- 0.7 u/ml), AML patients (n = 14, 2.0 +/- 2.1 u/ml) and AML-CR patients (n = 21, 1.4 +/- 1.2 u/ml). TNF-alpha production by the LPS-stimulated monocytes of the AML-CR patients (n = 54, 12.4 +/- 13.4 u/ml) was significantly higher than that of the normal controls (n = 21, 3.5 +/- 2.5 u/ml) and the AML patients (n = 17, 2.6 +/- 2.4 u/ml), p < 0.01, but there were not any significant differences among the AML-CR patients and the ALL patients or the ALL-CR patients. We separated the AML-CR patients into 3 groups, depending on the length of their remission, and found that AML-CR patients with longer than 6 months (M) but less than 60 M (n = 21, 15.7 +/- 16.9 u/ml) and the patients with a remission longer than 60 M (n = 11, 18.2 +/- 15.9 u/ml) had significantly higher TNF-alpha production than that of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum soluble CD4, CD8 and IL-2R levels in adult acute myeloid leukemia in remission.

We have measured the serum levels of soluble CD4, CD8 and IL-2R in 43 patients with AML in complete remission (AML-CR). The sCD8 levels of AML-CR patients (443.9 +/- 224.4 u/ml) were significantly high as compared to that of the normal controls (177.1 +/- 76.3 u/ml), p < 0.01. The sIL-2R levels of AML-CR patients were 715.0 +/- 646.3 u/ml, which significantly differed when compared to 322.1 +/- 65.7 u/ml for the normal controls, p < 0.01. However, the sCD4 levels of AML-CR patients were 9.6 +/- 4.7 u/ml, which did not differ from the 8.3 +/- 2.6 u/ml of the normal controls. The AML-CR patients showed significantly increased sCD8 and sIL-2R levels at all ranges during the remission from one to 188 months. The sCD8 levels and sIL-2R levels of the AML-CR patients showed a close correlation, p < 0.01. Further, the sCD8 levels and lymphokine activated killer cell cytotoxic activity showed a close correlation, p < 0.05. The presence of the activation of anti-tumor immunity may be related to the continuance of the remission in the AML-CR patients.

Telecommunication and international health research.

Telecommunication will revolutionize how international medical research is completed. It is faster, more accurate, less expensive, and potentially more accessible than all other existing modes of communication. It is time for medical scientists to come into the age of electronic communication.

Axonal transport of angiotensin-converting enzyme in the rat striatonigral pathway.

We analyzed the transport of angiotensin-converting enzyme (kininase II, EC 3.4.15.1) in the striatonigral pathway by quantitative autoradiography using the specific converting enzyme inhibitor, 125I-351A. 125I-351A binding was studied at different time intervals after knife cut lesions of the striatonigral pathway. Twenty-four h after the lesion, accumulations of 125I-351A binding sites were observed both rostral and caudal to the lesioned site. No change in 125I-351A binding was observed at this time in the caudate putamen and substantia nigra. Ten days after the lesion, a significant decrease (58%) in 125I-351A binding was found in the pars reticulata of the ipsilateral substantia nigra. These results suggest that the angiotensin-converting enzyme is transported axonally in the rat striatonigral pathway.

Axonal transport of dopamine D1 receptors in the rat brain.

Binding of a specific dopamine D1 receptor antagonist, 125I-SCH 23982, was measured in rat brain sections by quantitative autoradiography at various time intervals, following a knife cut through the striatonigral pathway. Twenty-four hours after lesioning, accumulations of D1 receptor binding sites were found in sagittal sections both rostral and caudal to the lesion site. No other regions studied (caudate-putamen, nucleus accumbens, olfactory tubercle, and substantia nigra pars reticulata) showed any change in D1 receptor binding 24 h after the lesion. In brain sections obtained 10 days after lesioning, only the substantia nigra pars reticulata had a significant decrease in D1 receptors ipsilateral to the lesion. These findings suggest the possibility of a presence of bidirectional axonal transport of D1 receptors in rat striatonigral pathway.

Dopamine D1 receptor in rat brain: a quantitative autoradiographic study with 125I-SCH 23982.

We report the regional distribution and characteristics of 125I-SCH 23982 binding to D1 receptors in rat brain using a quantitative autoradiographic technique. The substantia nigra pars reticulata, the caudate putamen, the nucleus accumbens and the olfactory tubercle had a single class of high affinity binding sites for 125I-SCH 23982. Binding sites were also present in a discrete, continuous band connecting the caudate putamen with the substantia nigra.