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Hatomamicin, a new alkaloid antibiotic, was isolated from the culture filtrate of a strain of Saccharopolyspora. The antibiotic was extracted with EtOAc and purified by silica gel column chromatography. The free alkaloid was obtained as pale yellowish prisms from CH3CN solution. It exhibits antimicrobial activity against Gram-positive organisms. The apparent molecular formula of hatomamicin was determined to be C22H31NO5. The structure has been established by a combination of spectroscopic and X-ray crystallographic studies.

A new Philadelphia chromosome (Ph1)-positive cell line, designated TOM-1, was derived from bone marrow cells of a patient with Ph1-positive acute lymphocytic leukemia (ALL). The TOM-1 cells were positive for Ia and B1 antigens and terminal deoxynucleotidyl transferase (TdT) but negative for common ALL antigen. Although neither surface Ig nor cytoplasmic Ig was detected, the TOM-1 cells contained rearranged immunoglobulin-H chain genes but retained germ-line kappa chain and germ-line T cell receptor beta-chain genes. These results indicate that the TOM-1 cells reside as the progenitor of pre-B cells. We have investigated the chromosome 22 breakpoint and c-abl gene expression in the TOM-1 cells. We found that the breakpoint on chromosome 22 was within the breakpoint cluster region (bcr) in the TOM-1 cells. We also found the breakpoints within or near bcr in four of six Ph1-positive ALL cases, similar to the findings in Ph1-positive CML cases. Amplification of the c-abl gene was not detected in the TOM-1 cells. The leukemic cells isolated from a patient with CML in myeloid crisis contained a novel 8-kilobase (kb) abl-related messenger RNA (mRNA), but the TOM-1 cells contained c-abl transcripts of only normal sizes, despite the fact that they showed the bcr gene rearrangement.

Sea urchin embryos were labeled with [3H]adenosine at two developmental stages (morula and prism) and the labeled acid-soluble nucleotides were fractionated successively by column chromatography with DEAE-Sephadex and DEAE-cellulose, and by thin-layer chromatography on a PEI-cellulose plate. Significant radioactivity was detected on the PEI-cellulose plate at the region of diadenosine 5',5'''-P1,P4-tetraphosphate (AP4A). After treatment of this fraction with phosphodiesterase, the radioactivity was all recovered in the AMP region, while alkaline phosphatase had no effect on the AP4A fraction. The present result suggests that AP4A is actively synthesized in the sea urchin embryos.

A case of polycythemia vera with an inhibitor against factor XII was reported. A 60-year-old female was admitted to Hokkaido University School Hospital because of erythrocytosis and hepatosplenomegaly. The hemoglobin was 22.5 g/dl and white cell count was 9,500/microliters without immature cells. The platelet count was 484,000/microliters. Bone marrow specimens showed marked hypercellularity. Philadelphia chromosome was not found on chromosome analysis. She was diagnosed as polycythemia vera according to the criteria of polycythemia Vera Study Group. Activity of factor XII was found to be decreased on the initial examination, but she had no personal and familial history of bleeding. In order to clarify the cause of decreased activity of factor XII, her plasma was mixed with normal plasma, and then examined PTT using factor XII deficient plasma. Her plasma mixed with equivalent normal plasma did not show the correction of prolonged PTT. It was suggested that an inhibitor of her plasma was included in the IgG fraction using gel chromatography. The patient was treated with phlebotomy and administration of N4-palmitoyl (1- -D-arabinofurasyl) cytosine (derivative of cytosine arabinoside; PLAC) 200 mg/day and Busulfan (1 mg/day). Factor XII was not corrected by phlebotomy, but corrected gradually by administration of PLAC and Busulfan.

The enzyme activity hydrolysing diadenosine 5,5'-P1, P4-tetraphosphate (AP4A) was demonstrated in the embryonic extract of sea urchin. The enzyme activity was preferentially inhibited by ZnCl2 and by high concentrations of isobutylmethylxanthine, indicating that two types of the enzyme, (AP4A) hydrolase and non-specific phosphodiesterase, are related to the degradation of (AP4A) in sea urchin embryos. The (AP4A)-hydrolysing activity was not detectable in the unfertilized eggs because of the presence of a high-molecular weight (HMW) and thermolabile inhibitory factor. Though the enzymes were activated immediately after fertilization, no cell cycle-dependent fluctuations in their activities were observed.

In acute lymphoblastic leukemia (ALL) of a 19-year-old woman, blast cells in the blood and bone marrow contained peculiar large cytoplasmic inclusions. The inclusions, measuring 0.5-3.5 micron in diameter, were stained with methylene blue, toluidin blue, pyronin, and periodic acid-Schiff. Activities for acid phosphatase and alpha naphthyl butyrate esterase were not detected in the inclusions. The cytochemical findings indicated that the inclusions contained basophilic material and polysaccharides and that they were not lysosomal in nature. In electron microscopy, the inclusions were membrane bound and contained densely packed microvesicles, measuring 40-70 nm in diameter; amorphous electron-dense material; and whorled membranous figures. The microvesicles often had a nucleoid-like core and resembled viruses in size and structure.

Forty-two cases of hematological malignancy (18 cases of CML, three cases of polycythemia vera, 10 cases of malignant lymphoma and 11 cases of multiple myeloma) were treated with MCNU. The results obtained were as follows. MCNU was markedly effective on CML cases, being especially useful during the chronic phase, and a partial remission was observed in one of three patients with CML blastic crisis. A good response was observed in all cases with polycythemia vera. In some cases of malignant lymphoma, a fair response was observed. No response was observed in any of the cases of multiple myeloma. Myelosuppression was a major side effect of MCNU, but other side effects other than melena were not severe.