Dose-response relations for dicentric yields in GO lymphocytes of man and crab-eating monkey following acute and chronic gamma-irradiations.

A comparison has been made of dicentric yields in G₀ lymphocytes between man and crab-eating monkey, Macaca fascicularis, after acute and chronic γ-irradiations. With acute irradiation (49.6 rad/min) there was no significant difference between them, but for the chronic irradiation (17.1 rad/h) a significant difference was observed between the species. When the dose-response relations were fitted to the linear-quadratic model (Y = D + βD²), the species-difference observed for chronic irradiation was almost entirely due to change in the value of β. In addition, after chronic irradiation the β-value for monkey was almost negligible, but that for man was significant. Post-irradiation incubation experiment showed that cells with dicentrics were partly eliminated during the course of chronic irradiation, because there were appreciable reductions of dicentric yields (ca. 25% for both man and monkey at 400 rad) together with mitotic indices (ca. 30% and 60% for man and monkey, respectively, at 400 rad). Accordingly, it would be reasonable to postulate that G₀ repair for dicentrics other than selection mechanism must play a major role in the effects of low dose rate. It can be further suggested that G₀-repair capacity for chromosal damages leading to dicentrics may be different among different primate species.     

Processing of mengovirus precursor polypeptides in the presence of zinc ions and sulfhydryl compounds.

The effect of zinc ions on the post-translational cleavage of mengovirus polypeptides has been examined. The cleavage of the "A" precursor, which gives rise to the capsid proteins, was the most sensitive at concentrations of zinc chloride from 0.1 to 1.0 mM. Beta-mercaptoethanol and dithiothreitol antagonized the zinc-promoted inhibtion of clevage. Our results indicate that zinc ions interfere with the proper folding of the nascent polypeptide precursor rather than inhibit the proteases responsible for the cleavages. Thus, proper folding of mengovirus polypeptide "A" appears to be necessary for subsequent processing by proteases.     

Studies of the genetic mechanism of radiation-induced mitotic segregation in yeast

Summary Sectoring was induced with x-rays or ultraviolet in a diploid yeast strain heterozygous for seven genes located on one chromosome arm. The frequencies of sectoring of different genes were approximately linearly related to their distance from the centromere. If two or more adjacent genes sectored, the event could be explained by mitotic crossing over. Sectoring of single genes, however, was mostly nonreciprocal and resembled a conversion-type event. Approximately 80% of the sectored colonies could be explained single mitotic crossovers in one of the intergenic regions.     

Letter to the editor Synthesis of 16-fluoromethylene-prostaglandin F2α

Prostaglandin (PG) E₂, thromboxane (TX) B₂ and the stable breakdown product of prostacyclin, 6-oxo-PGF_1α are present in carrageenin-induced inflammatory exudates. Carrageenin-impregnated polyester sponges were implanted subcutaneously in rats and inflammatory exudates were collected 4–192 h after implantation. The concentrations of cyclo-oxygenase products in sponge fluids was measured by radioimmunoassay after extraction and purification. All three products were detectable after 4 h and reached a peak at 12–24 h. Mean TXB₂ concentrations reached 74 ng/ml at 12 h but decreased to less than 10 ng/ml after 24 h. PGE₂ concentrations were 65 ng/ml at 24 h, after which there was no significant increase and then dropped to about 20 ng/ml between 96 and 192 h. 6-oxo-PGF_1α reached a concentration of 33 ng/ml at 24 h which did not change significantly until levels fell to less than 10 ng/ml between 96 and 192 h. The presence of PGE₂, TXB₂ and 6-oxo-PGF_1α was confirmed by gas-liquid chromatography and mass spectrometry. Total leukocyte numbers increased steadily and were at their highest (116.0 × 10⁶ cells/ml) at 192 h. These results suggest that thromboxanes and prostacyclin, as well as PGE₂, contribute to the acute inflammatory response.     

EFFECT OF EHRLICH ASCITES CELL CHALONE ON NASCENT DNA SYNTHESIS IN ISOLATED NUCLEI

Ehrlich Ascites Tumor (EAT) chalone has been shown to inhibit nascent DNA synthesis by inhibiting DNA polymerase α and β (Nakai, 1976), but one of the problems in studying eurkaryotic DNA replication has been the relative impermeability of the cell membrane to precursors and macromolecules; hence, to circumvent this restriction without sacrificing the integrity of the replication process, a broken cell system utilizing nuclei in aqueous media was investigated. Isolated nuclei appear to continue the process of DNA replication that was proceeding in vivo before their isolation and under optimal conditions are able to initiate new synthesis (Fraser & Huberman, 1977). The effects of partially purified EAT chalone on nascent DNA could be studied directly in this nuclear system, which excluded effects of the cell membrane, nucleotide pools and other cytosol elements. A concentration-related inhibition of [³H]thymidine triphosphate ([³H]-dTTP) incorporation was noted over a chalone range of 50–200 μg/ml. It appears that chalone can inhibit DNA polymerase α directly within the nucleus without an intermediate step such as a cell membrane receptor.     

Impacts of Perinatal Dioxin Exposure on Motor Coordination and Higher Cognitive Development in Vietnamese Preschool Children: A Five-Year Follow-Up

Dioxin concentrations remain elevated in the environment and in humans residing near former US Air Force bases in South Vietnam. Our previous epidemiological studies showed adverse effects of dioxin exposure on neurodevelopment for the first 3 years of life. Subsequently, we extended the follow-up period and investigated the influence of perinatal dioxin exposure on neurodevelopment, including motor coordination and higher cognitive ability, in preschool children. Presently, we investigated 176 children in a hot spot of dioxin contamination who were followed up from birth until 5 years old. Perinatal dioxin exposure levels were estimated by measuring dioxin levels in maternal breast milk. Dioxin toxicity was evaluated using two indices; toxic equivalent (TEQ)-polychlorinated dibenzo-p-dioxins/furans (PCDDs/Fs) and concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Coordinated movements, including manual dexterity, aiming and catching, and balance, were assessed using the Movement Assessment Battery for Children, Second Edition (Movement ABC-2). Cognitive ability was assessed using the nonverbal index (NVI) of the Kaufman Assessment Battery for Children, Second Edition (KABC-II). In boys, total test and balance scores of Movement ABC-2 were significantly lower in the high TEQ- PCDDs/Fs group compared with the moderate and low exposure groups. NVI scores and the pattern reasoning subscale of the KABC-II indicating planning ability were also significantly lower in the high TCDD exposure group compared with the low exposure group of boys. However, in girls, no significant differences in Movement ABC-2 and KABC-II scores were found among the different TEQ-PCDDs/Fs and TCDD exposure groups. Furthermore, in high risk cases, five boys and one girl highly exposed to TEQ-PCDDs/Fs and TCDD had double the risk for difficulties in both neurodevelopmental skills. These results suggest differential impacts of TEQ-PCDDs/Fs and TCDD exposure on motor coordination and higher cognitive ability, respectively. Moreover, high TEQ-PCDDs/Fs exposure combined with high TCDD exposure may increase autistic traits combined with developmental coordination disorder.     

Engineering analysis of the high-density heterotrophic cultivation of mung bean sprouts

This study investigated the heterotrophic growth behavior of mung beans cultivated in an individual bed under water supply. The fresh weight of mung beans in the bed was estimated, and changes in temperature, and oxygen and carbon dioxide concentrations were recorded during the cultivation period. The specific growth rate, oxygen uptake rate, and carbon dioxide evolution rate, based on the fresh weight in the bed, were calculated. Growth under heterotrophic cultivation can be classified into the following three stages. Reductions in specific oxygen uptake rate, specific carbon dioxide evolution rate, and specific energy production rate corresponded to that of specific growth rate. Indicators of biological activity related to oxygen and carbon dioxide were evaluated quantitatively for beds under high-density heterotrophic cultivation. Moreover, the results obtained from this study successfully demonstrate that there is a relationship between the growth of mung beans and indicators of biological activity.     

Three-dimensional structure of 4-amino-4-deoxychorismate lyase from Escherichia coli

4-Amino-4-deoxychorismate lyase (ADCL) is a member of the fold-type IV of PLP dependent enzymes that converts 4-amino-4-deoxychorismate (ADC) to p-aminobenzoate and pyruvate. The crystal structure of ADCL from Escherichia coli has been solved using MIR phases in combination with density modification. The structure has been refined to an R-factor of 20.6% at 2.2 A resolution. The enzyme is a homo dimer with a crystallographic twofold axis, and the polypeptide chain is folded into small and large domains with an interdomain loop. The coenzyme, pyridoxal 5'-phosphate, resides at the domain interface, its re-face facing toward the protein. Although the main chain folding of the active site is homologous to those of D-amino acid and L-branched-chain amino acid aminotransferases, no residues in the active site are conserved among them except for Arg59, Lys159, and Glu193, which directly interact with the coenzyme and play critical roles in the catalytic functions. ADC was modeled into the active site of the unliganded enzyme on the basis of the X-ray structures of the unliganded and liganded forms in the D-amino acid and L-branched-chain amino acid aminotransferases. According to this model, the carboxylates of ADC are recognized by Asn256, Arg107, and Lys97, and the cyclohexadiene moiety makes van der Waals contact with the side chain of Leu258. ADC forms a Schiff base with PLP to release the catalytic residue Lys159, which forms a hydrogen bond with Thr38. The neutral amino group of Lys159 eliminates the a-proton of ADC to give a quinonoid intermediate to release a pyruvate in accord with the proton transfer from Thr38 to the olefin moiety of ADC.