Cloning of aklavinone biosynthesis genes from Streptomyces galilaeus.

Aklavinone is an aglycone of aclacinomycin A which is an important antitumor drug. Genes for the biosynthesis of aklavinone were cloned from Streptomyces galilaeus 3AR-33, an aklavinone-producing mutant, by use of the actI and actIII polyketide synthase gene probes. Restriction mapping and Southern analysis of the DNA cloned in a lambda phage vector established that the DNA represented three different regions of the S. galilaeus 3AR-33 genome that contained 3.4, 2.5, and 4.1 kb BamHI fragments which hybridized with actIII. Of those, only the 3.4 kb fragment also hybridized with actI. Complementation experiments with specifically blocked mutants confirmed that the cloned 3.4 kb BamHI fragment contains the genes required for the early stage of polyketide synthesis in aklavinone biosynthesis.     

Effect of lidocaine on histamine release and Ca2+ mobilization from mast cells and basophils

Background : Various anesthetic drags have been known to induce allergic reactions, which have been caused by histamine release from mast cells/basophils. Although lidocaine is reported to suppress allergic reactions, there have been no reports about lidocaine's direct effects to inhibit histamine release from mast cells/basophils. Methods : We examined the effect of lidocaine on histamine release in vitro from freshly extracted as well as cultured mast cells and basophils. Additionally, the effects of lidocaine on intracellular calcium concentration were monitored by assessing Fura-2 signals in cultured cells. Results : Lidocaine (10^?3～10^?2 M: approximately 234～2340 μg/ ml) inhibited both the IgE-dependent and IgE-independent histamine release from all mast cells/basophils in a dose-dependent manner. However, lidocaine inhibited the IgE-dependent response more than the IgE-independent response (P<0.01). Lidocaine also inhibited increases in intracellular Ca²⁺ to a greater extent after IgE-dependent stimulation as compared with IgE-independent stimulation. The degree of the inhibition of histamine release by lidocaine appeared to parallel decreases in Ca²⁺ mobilization. Conclusions : Our results indicate that lidocaine directly inhibits histamine release from both rodent mast cells and human basophils in vitro at concentrations from 10^?3 to 10^?2 M (234 to 2340 μg/ml). That may be influenced by Ca²⁺ mobilization. Although these results are not immediately relevant to clinical practice, allergic reaction caused by direct effect of lidocaine seems to be impossible.     

Brain metastases from Wilms' tumor without systemic involvement--a case report and review]

A 3-year-old boy presented with multiple brain metastases 21 months after the resection of stage II Wilms' tumor. Metastasis to other organs was not found. He was treated by total removal of a large metastatic tumor in the left temporal lobe and post-operative radiotherapy and chemotherapy. He has been in complete remission for 20 months after surgery. Cerebral metastasis from Wilms' tumor without systemic metastases is very rare. It is speculated that brain metastases occurred in this patient because most of the anticancer agents used in the primary treatment for Wilms' tumor were not able to cross the blood brain barrier.     

Uptake of bleomycin by human brain tumours

The uptake of bleomycin (BLM) by various types of brain tumours after intravenous or intrathecal administration was investigated by bioassay in 67 patients. The correlation between the BLM distribution and the type and characteristics of brain tumours was studied.     

A case of multiple cerebral aneurysms caused by cardiac myxoma

A case of neoplastic aneurysm caused by left atrial myxoma is reported. The patient was a 50-year-old woman who has been suffered from occasional vertigo and syncopal attack. She was admitted with a sudden loss of consciousness and cerebellar ataxia on December 1, 1983. Cerebral angiogram revealed multiple aneurysms in the periphery of both middle cerebral arteries and obstruction of the right superior cerebellar artery. Echocardiography displayed a cardiac myxoma in the left atrium. She suddenly died from recurrent cerebral embolism on January 7, 1984. The diagnosis was confirmed by the autopsy. The histopathological examination revealed that the wall of cerebral arteries were destroyed by the tumor cells of myxoma, and it caused cerebral aneurysms. We presented the detail of this case, and discussed about a mechanism and a treatment of neoplastic aneurysms.     

Regional differences in inhibition and recovery of protein synthesis after transient hindbrain ischaemia of gerbils

Regional protein synthesis was estimated autoradiographically in a model of transient hindbrain ischaemia of gerbils. In studies of 5 min ischaemia followed by 5 min recirculation, incorporation of [14C]valine into the TCA-insoluble protein fraction was not affected. In studies of 15 min ischaemia followed by 5 min recirculation, incorporation of the tracer into the protein fraction was severely depressed in the ischaemic lesion of the brain stem and cerebellum. However, the granular layer of the cerebellar cortex had partially preserved protein synthesis. When recirculation time was extended to 2 h after 30 min ischaemia, protein synthesis of the cerebellar cortex almost recovered to the full level of the control. However, in the pontine grey matter, inferior colliculus and vestibular nucleus, a significant reduction in protein synthesis persisted. These results indicate that protein synthesis in the pontine grey matter, inferior colliculus and vestibular nucleus are selectively inhibited by ischaemia. Further its recovery after recirculation is slow. The cerebellar cortex is less vulnerable to ischaemia, and recovery is relatively fast. The regional heterogeneity of protein synthesis is neither due to the degree of ischaemia in this model nor the extent of postischaemic hypoperfusion. Factors that influence protein synthesis in this ischaemic model are discussed.     

Meningeal gliomatosis models as a chemosensitivity assay system

Experimental models of meningeal gliomatosis (MG) have been produced by intracisternal inoculation of C6 and 9L glioma cells into Wistar and Fisher 344 rats, respectively. Chemotherapy of these models and in vitro chemosensitivity assay for these cell lines were studied with ACNU, BCNU and VM-26. In vitro chemosensitivity assay revealed that 9L cells were sensitive to all of the anticancer drugs above, and that C6 cells were resistant to ACNU and BCNU, but not to VM-26. In vivo experiment, the survival time of the rats inoculated with 9L glioma cells (9LMG) was prolonged by both ACNU and BCNU but not by VM-26. None of these drugs were effective against the rats inoculated with C6 glioma cells (C6MG). It is concluded that the result of in vitro chemosensitivity assay is not always correlative with that of in vivo. This implies that an in vivo chemosensitivity assay system including MG models is indispensable in researching into chemotherapy of brain tumor.