Kazuo Nomiyama

A novel recombinant adeno-associated virus vaccine induces a long-term humoral immune response to human immunodeficiency virus

Recombinant adeno-associated virus (AAV) has attracted tremendous interest as a promising vector for gene delivery. In this study we have developed an HIV-1 vaccine, using an AAV vector expressing HIV-1 env, tat, and rev genes (AAV-HIV vector). A single injection of the AAV-HIV vector induced strong production of HIV-1-specific serum IgG and fecal secretory IgA antibodies as well as MHC class I-restricted CTL activity in BALB/c mice. The titer of HIV-1-specific serum IgG remained stable for 10 months. When AAV-HIV vector was coadministered with AAV-IL2 vector, the HIV-specific cell-mediated immunity (CMI) was significantly enhanced. Boosting with AAV-HIV vector strongly enhanced the humoral response. Furthermore, the mouse antisera neutralized an HIV-1 homologous strain, and BALB/c mice immunized via the intranasal route with an AAV vector expressing the influenza virus hemagglutinin (HA) gene showed protective immunity against homologous influenza virus challenge. These results demonstrate that AAV-HIV vector immunization may provide a novel and promising HIV vaccination strategy.

Respiratory retention, uptake and excretion of organic solvents in man

SummaryMechanisms of respiratory retention of organic solvents are discussed. Respiratory retention, uptake and excretion were estimated separately in 66 men and women volunteer students exposed to benzene, toluene, n-hexane, trichloroethylene, acetone, ethyl acetate and ethyl alcohol.After 2 hrs exposure, respiratory retention reached constant levels; these differed for each of the 7 organic solvents tested. No sex difference in retention was observed. Respiratory excretion values differed as 100 × concentration in expired air immediately following breathing of solvent free air/concentration of solvent in air breathed during exposure. Men excreted more toluene and trichloroethylene than did women. Uptake varied 27–60%.

Respiratory elimination of organic solvents in man

SummaryRespiratory elimination of benzene, toluene, n-hexane, trichloroethylene, acetone, ethyl acetate and ethyl alcohol were studied after exposure in human volunteers to those solvents.1.Solvent concentration in expired air decreased rapidly with time after the cessation of exposure and the decrease was expressed as an equation. Ethyl acetate and ethyl alcohol in expired air decreased faster than did other organic solvents. The decrease was very slow in acetone.2.Large amounts of retained acetone, benzene and n-hexane were eliminated through the lungs as unchanged solvents, while the amount of eliminated ethyl acetate was almost negligible.3.The ratio of respiratory elimination to the inhaled (environmental) organic solvent suggested that the determination of respiratory concentration is helpful for estimating environmental benzene, acetone, trichloroethylene and toluene concentration.

Early signs of cadmium intoxication in rabbits

Abstract Nineteen male rabbits were given sc injections of cadmium chloride at dose levels of 15, 6 and 1.5 mg Cd/kg/day. Body weight, renal function and urinary excretion of enzymes were periodically examined. Loss of body weight and increase of urinary excretion of protein, alkaline phosphatase and acid phosphatase were found to be early warning signs suggestive of renal injuries. Temporal dysfunction of distal tubules, accompanied by warning signs, and renal dysfunction appeared later. Signs of intoxication were found to be closely correlated with the accumulated dose of cadmium. The cumulative median lethal dose was estimated to be 40–44 mg Cd/kg. Stop-flow analysis, performed at the end of successive cadmium administrations, revealed proximal tubular dysfunction as well as glomerular and distal tubular dysfunction.

Assay of urinary enzymes in toxic nephropathy

Abstract The activity of several enzymes found in rabbit urine was determined at various time intervals after a single iv injection of uranyl acetate. Significant increases occurred in the activity of alkaline phosphatase, glutamicoxaloacetic transaminase and glutamic-pyruvic transaminase and appeared earlier than pathologic changes indicated by urinalysis or renal function tests. The increased activity of urinary enzymes was found to be almost proportional to the dose 24 hr after uranyl administration. Urinary enzyme values soon returned to normal levels whereas renal function tests remained depressed. These findings suggest that the increased activity of enzymes in the urine results mainly from renal cellular injury. Clearance studies indicate that most urinary enzymes after uranyl administration were released from renal tubular cells. These findings suggest that the assay of urinary enzymes may be useful in the detection of early injury in renal tubules. Specifically, proximal tubular injury is indicated by increased alkaline phosphatase activity and distal tubular injury by an elevation of lactic dehydrogenase.

Metabolism of trichloroethylene in human

SummaryRetention and respiratory elimination of trichloroethylene, and urinary excretion of trichloroethylene metabolites were determined in ten volunteer students exposed to 250–380 ppm trichloroethylene for 160 min.1.Retention amounted to 36% of the inhaled trichloroethylene.2.Trichloroethylene was eliminated through respiration after exposure, and the concentration in expired air decreased exponentially with a rate constant k∶:0.14 hour−1. Respiratory elimination of trichloroethylene was 16% of the retained trichloroethylene.3.Urinary excretion of total trichloro-compounds decreased exponentially with k∶:0.23 day−1 in males and 0.20 in females.4.Urinary excretion of trichloroacetic acid and trichloroethanol were 32.6% and 48.6% in males, and 43.9% and 42.7% of the retained trichloroethylene in females.5.Trichloroacetic acid in females was found to be 2–3 times more than that in males for the first 24 hours after exposure. Trichloroethanol, on the contrary, was excreted twice more in males than in females for the first 12 hours. Therefore, the trichloroethanol to trichloroacetic acid ratio was significantly different between males and females by 5.5 times for the first 24 hours after exposure.6.These findings suggest a sex difference in human metabolism of trichloroethylene. Urinary total trichloro-compounds form a better index of trichloroethylene exposure than urinary trichloroacetic acid.

Estimation of trichloroethylene exposure by biological materials.

SummaryThe relation between concentration of trichloroethylene in environmental air and trichloroethylene in expired air, as well as urinary excretion of total trichloro-compounds was studied. Application of the derived equations to data previously reported leads to close agreement between actual concentration of trichloroethylene in environmental air and that calculated either from respiratory elimination of trichloroethylene measured 2–6 hours after exposure or from urinary excretion of total trichloro-compounds determined 2–6 days later.

Urinary low-molecular-weight proteins in Itai-Itai disease

Abstract The etiology of the so-called Itai-Itai disease has been thought to relate to malnutrition and dietary cadmium exposure. Itai-Itai disease, named after its severe pain, was endemic in Zinzu River area in Japan; its characteristic signs and symptoms were osteomalacia and renal tubular dysfunction. Urinary low-molecular-weight proteins have been reported to be characteristic of renal tubular dysfunction. The components of urinary low-molecular-weight proteins in Itai-Itai disease are suggested in this paper to be retinol-binding protein and β2-microglobulin as determined by gel filtration, disc electrophoresis and immunoassay. Furthermore, vitamin D administration at a large dose is discussed and thought to contribute to the aggravation of renal tubular dysfunction in Itai-Itai disease.