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Abstract Background To address the clinical and virological significance of a high HTLV-1 proviral load (VL) in practical blood samples from asymptomatic and symptomatic carriers, we simultaneously examined VL and clonal expansion status using polymerase chain reaction (PCR) quantification (infected cell % of peripheral mononuclear cells) and Southern blotting hybridization (SBH) methods. Results The present study disclosed extremely high VL with highly dense smears with or without oligoclonal bands in SBH. A high VL of 10% or more was observed in 16 (43.2%) of a total of 33 samples (one of 13 asymptomatic carriers, 8 of 12 symptomatic carriers, and 7 of 8 patients with lymphoma-type ATL without circulating ATL cells). In particular, an extremely high VL of 50% or more was limited to symptomatic carriers whose band findings always contained at least dense smears derived from polyclonally expanded cells infected with HTLV-1. Sequential samples revealed that the VL value was synchronized with the presence or absence of dense smears, and declined at the same time as disappearing dense smears. Dense smears transiently emerged at the active stage of the underlying disease. After disappearance of the smears, several clonal bands became visible and were persistently retained, explaining the process by which the clonality of HTLV-1-infected cells is established. The cases with only oligoclonal bands tended to maintain a stable VL of around 20% for a long time. Two of such cases developed ATL 4 and 3.5 years later, suggesting that a high VL with oligoclonal bands may be a predisposing risk to ATL. Conclusion The main contributor to extremely high VL seems to be transient emergence of dense smears detected by the sensitivity level of SBH, corresponding to polyclonal expansion of HTLV-1-infected cells including abundant small clones. Major clones retained after disappearance of dense smears stably persist and acquire various malignant characteristics step by step.

The article presents a study which synthesizes 4-hydroxyisoleucine (4-HIL) by aldolase-transaminase coupling reaction and basic characterization of the aldolase purified Arthrobacter simplex AKU 626. It describes the screening of an aldolase-producing bacterium. It is revealed that A. simplex AKU 626 synthesized 4-HIL from acetaldehyde, alpha-ketobutyrate and L-glutamate with Escherichia coli harboring the branched chain amino acid transaminase gene.

Linalool oxide is frequently used as a flavoring agent, however, data on its toxicity is limited. In this study, we performed a 13-week subchronic toxicity study of linalool oxide (furanoid) in male and female Crl:CD(SD) rats. Doses of 0, 80, 250, and 800 mg/kg body weight (bw) per day were orally administered by gavage, using corn oil as the vehicle. Abnormal gait in both sexes and decreased locomotor activity in males were observed in the 800 mg/kg group. Reduced body weight gain was noted in both sexes at 800 mg/kg and at 250 mg/kg in males. In the 800 mg/kg group, serum biochemistry showed increased γ-glutamyl transpeptidase and decreased glucose in both sexes, increased total protein in males, and increased total cholesterol and phospholipids in females, suggesting that linalool oxide may have adverse effects on the liver. Increased relative and/or absolute liver weights, centrilobular hepatocellular hypertrophy in both sexes, and periportal microvesicular fatty changes in females were observed in the 800 mg/kg group. Increased relative liver weights and decreased serum glucose levels were observed in the 250 mg/kg male and female groups, respectively. Increased serum magnesium levels and relative kidney weights were observed in both sexes in the 800 mg/kg group, suggesting possible adverse effects of linalool oxide. Although histopathology showed accumulation of hyaline droplets in the male kidneys, immunohistochemistry revealed α 2u -globulin nephropathy, which was not considered toxicologically significant. These results indicate that the no-observed-adverse-effect level of linalool oxide was 80 mg/kg bw/day for both sexes., Competing Interests: The authors declare no conflict of interest., (©2024 The Japanese Society of Toxicologic Pathology.)

The substrate specificities of deuterolysin, a 19-kDa zinc-protease (EC 3.4.24.39) from Aspergillus oryzae, were investigated at pH 9.0 with various fluorogenic acyl-peptide-4-methylcoumaryl-7-amides (peptide-MCAs). N-Butoxycarbonyl-Arg-Val-Arg-Arg-MCA was the best substrate for deuterolysin. We therefore measured its kinetic parameters. Deuterolysin had high activity toward the peptide bonds next to pairs of basic residues in calf thymus histone H4. The specificity of cobalt-substituted deuterolysin (Co-deuterolysin) for peptide-MCAs was similar to that of native deuterolysin. The CD spectrum of Co-deuterolysin was similar to that of the native deuterolysin. The metal coordination sphere of Co-deuterolysin was analyzed by Q-band (33.9570 GHz) electron paramagnetic resonance (EPR) spectroscopy. Using computer simulation of EPR, we found the g principal values to be g(xx) = 5.20, g(yy) = 4.75, and g(zz) = 2.24; the metal center was a divalent cobalt ion in a high spin state.