Cancer chemotherapy and somatic cell mutation

The occurrence of a second neoplasm is one of the major obstacles in cancer chemotherapy. The elucidation of the genotoxic effects induced by anti-cancer drugs is considered to be helpful in identifying the degree of cancer risk. Numerous investigations on cancer patients after chemotherapy have demonstrated: (i) an increase in the in vivo somatic cell mutant frequency (Mf) at three genetic loci, including hypoxanthine–guanine phosphoribosyl-transferase (hprt), glycophorin A (GPA), and the T-cell receptor (TCR), and (ii) alterations in the mutational spectra of hprt mutants. However, the time required for and the degree of such changes are quite variable among patients even if they have received the same chemotherapy, suggesting the existence of underlying genetic factor(s). Accordingly, some cancer patients prior to chemotherapy as well as patients with cancer-prone syndrome have been found to show an elevated Mf. Based on the information obtained from somatic cell mutation assays, an individualized chemotherapy should be considered in order to minimize the risk of a second neoplasm.     

Involvement of the acyl chain of ceramide in carbohydrate recognition by an anti-glycolipid monoclonal antibody: the case of an anti-melanoma antibody,M2590, to GM3-ganglioside

The effect of the chain length of the fatty acid residue of the ceramide moiety of ganglioside G_M3 on the binding ability of monoclonal antibody M2590, which is specific for the carbohydrate structure of G_M3-ganglioside, was examined by means of a direct binding assay on thin layer chromatography plates (TLC immunostaining) and a quantitative enzyme-linked immunosorbent assay (ELISA). Derivatives of G_M3 with a long fatty acid chain reacted with the M2590 antibody, but those with a short fatty acid chain showed no reaction in either assay system. These results suggested that the acyl fatty acid moiety of the ganglioside played an important role in the formation or maintenance of the antigenic structure of the carbohydrate moiety of the ganglioside.     

Successful treatment for perinephric abscess with recombinant human granulocyte colony-stimulating factor following nephrectomy in a patient of myelodysplastic syndrome: A case report

The 35-year-old man with myelodysplastic syndrome (MDS) and granulocytopenia with dry cough and high fever was eventually found to have a left perinephric abscess ofStaphylococcus aureus. He underwent left nephrectomy and drainage of perinephric space in conjunction with appropriate antibiotics. However, because of persistent granulocytopenia,Staph. aureus never cleared up with formation of only poor granulation. Recombinant human granulocyte colony-stimulating factor (G-CSF) was added to the above treatment leading to prompt improvement in granulocytopenia and emergence of the good granulation tissue. G-CSF will probably become one of the important agents in treating MDS with granulocytopenia.     

Effect of pressure on thermal insulation in humans wearing wet suits

The present work was undertaken to determine the critical water temperature (Tcw), defined as the lowest water temperature a subject can tolerate at rest for 3 h without shivering, of wet-suited subjects during water immersion at different ambient pressures. Nine healthy males wearing neoprene wet suits (5 mm thick) were subjected to immersion to the neck in water at 1, 2, and 2.5 ATA while resting for 3 h. Continuous measurements of esophageal (T(es)) and skin (Tsk) temperatures and heat loss from the skin (Htissue) and wet suits (Hsuit) were recorded. Insulation of the tissue (Itissue), wet suits (Isuit), and overall total (Itotal) were calculated from the temperature gradient and the heat loss. The Tcw increased curvilinearly as the pressure increased, whereas the metabolic heat production during rest and immersion was identical over the range of pressure tested. During the 3rd h of immersion, Tes was identical under all atmospheric pressures; however, Tsk was significantly higher (P less than 0.05) at 2 and 2.5 ATA compared with 1 ATA. A 42 (P less than 0.001) and 50% (P less than 0.001), reduction in Isuit from the 1 ATA value was detected at 2 and 2.5 ATA, respectively. However, overall mean Itissue was maximal and independent of the pressure during immersion at Tcw. The Itotal was also significantly smaller in 2 and 2.5 ATA compared with 1 ATA. The Itissue provided most insulation in the extremities, such as the hand and foot, and the contribution of Isuit in these body parts was relatively small. On the other hand, Itissue of the trunk areas, such as the chest, back, and thigh, was not high compared with the extremities, and Isuit played a major role in the protection of heat drain from these body parts.     

Critical water temperature during water immersion at various atmospheric pressures

The present work was undertaken to determine the effect of atmospheric pressure [ranging from a high altitude of 4,300 m above sea level or 0.6 atmospheres absolute (ATA) to depths of 10 m deep or 2 ATA] on the critical water temperature (Tcw), defined as the lowest water temperature a subject can tolerate at rest for 2 h without shivering, of the unprotected subject during water immersion. Nine healthy males wearing only shorts were subjected to immersion to the neck in water at 0.6, 1, and 2 ATA while resting for 2 h. Continuous measurements included esophageal (Tes) and skin (Tsk) temperatures, direct heat loss from the skin (Htissue), and insulation of the tissue (Itissue). The Tcw was significantly higher at 0.6 ATA than 1 and 2 ATA: however, Tcw at 1 ATA was identical to that at 2 ATA. The metabolic heat production remained unchanged among the pressures. During the 2-h immersion in Tcw, Tes was identical among all atmospheric pressures: however, Tsk was significantly higher (P less than 0.05) at 0.6 ATA and was identical between 1 and 2 ATA. The overall mean Itissue was near maximal during immersion in Tcw in each pressure, and no difference was detected among the pressures. However, Itissue at the acral extremities (arm, hand, and foot) decreased significantly at 0.6 ATA, and subsequently heat loss from these parts was increased, which elevated an extremity-to-trunk heat loss ratio to 1.4 at 0.6 ATA from 1.1 at 1 and 2 ATA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increase in nucleoside diphosphatase in rat brain striatum lesioned with kainic acid

The activity of ammoniagenesis from guanine nucleotides was found to increase significantly in rat brain after infusion of kainic acid into the striatum. Among the enzymes involved in degrading guanine nucleotides, nucleoside diphosphatase was markedly increased in the lesioned striatum. The enzyme activity began to increase 2 days after the infusion, and reached the maximum on the 13th day, the level being 4 times as high as that of the intact contralateral region. The increased activity was due to Type L enzyme, judging from its substrate specificity. Puromycin and cycloheximide inhibited this increase, indicating that the increased activity resulted from an increase in the net synthesis of the enzyme. These findings suggest that Type L NDPase might play some important roles in gliosis after neuronal lesion.     

Identification of the region including the epitope for a monoclonal antibody which can neutralize human parvovirus B19.

In this study, we identified a region in the human parvovirus structural protein which involves the neutralization of the virus by a monoclonal antibody and site-specific synthetic peptides. A newly established monoclonal antibody reacted with both viral capsid proteins VP1 and VP2. The epitope was found in six strains of independently isolated human parvovirus B19. The monoclonal antibody could protect colony-forming unit erythroid in human bone marrow cell culture from injury by the virus. The monoclonal antibody reacted with only 1 of 12 peptides that were synthesized according to a predicted amino acid sequence based on nucleotide sequences of the coding region for the structural protein of B19 virus. The sequence recognized by the antibody was a site corresponding to amino acids 328 to 344 from the amino-terminal portion of VP2. This evidence suggests that the epitope of the viral capsid protein is located on the surface of the virus and may be recognized by virus-neutralizing antibodies.     

A novel MHC class I-related molecule expressed on mouse thymic stroma cells and mature lymphocytes

A monoclonal antibody (mAb) TP-3 has been established by immunizing rats with the BALB/c mouse thymic epithelial cell line TEL-2. The TP-3 antigen is expressed on stroma cells of thymus, spleen, and lymph node in syngeneic BALB/c mice (H-2 ^d ). This antigen is also expressed at a low level on the cell surface of immature thymocytes, and at a high level on mature T and B cells. In allogeneic mice such as C57BL/6 (H-2 ^b ) or C3H (H-2 ^k ), no cells expressed the TP-3 antigen. Using H-2 congenic mice, reactivity with mAb TP-3 was found to map to a region of H-2D ^d L ^d or between D ^d and Qa, suggesting that TP-3 is a major histocompatibility complex (MHC) class I antigen. However, immunoprecipitation analysis indicated that this antigen is not identical to the classical mouse class I molecules in terms of molecular size, antigenicity, and tissue distribution.     

Gene structure and expression of a tobacco endochitinase gene in suspension-cultured tobacco cells

We have isolated and characterized the genomic clone CHN50 corresponding to tobacco basic endochitinase (E.C.3.2.1.14). DNA sequence and blotting analysis reveal that the coding sequence of the gene present on CHN50 is identical to that of the cDNA clone pCHN50 and, moreover, the CHN50 gene has its origin in the progenitor of tobacco, Nicotiana sylvestris. Tobacco basic chitinases are encoded by a small gene family that consists of at least two members, the CHN50 gene and a closely related CHN17 gene which was characterized previously. By northern blot analysis, it is shown that the CHN50 gene is highly expressed in suspension-cultured tobacco cells and the mRNA accumulates at late logarithmic growth phase. To identify cis-DNA elements involved in the expression of the CHN50 gene in suspensioncultured cells, the chimeric gene consisting of 1.1 kb CHN50 5 upstream region fused to the coding sequence of -glucuronidase (GUS) was introduced by electroporation into protoplasts isolated from suspension-cultured tobacco cells. Transient GUS activity was found to be dependent on the growth phase of the cultured cells, from which protoplasts had been prepared. Functional analysis of 5 deletions suggests that the distal region between -788 and -345 contains sequences that potentiate the high-level expression in tobacco protoplasts and the region (-68 to -47) proximal to the TATA box functions as a putative silencer.