Biomedical subjects
Publications and source records attributed to J L Li.
We would consider not only the significance level alpha, but also the power 1-beta, when making a significance test. This paper presents the method of finding the power of the significance test of a multiple regression equation, and the method of finding the necessary sample size, and has listed the power table and the sample size table for ready reference.
A simple and rapid method for detecting Plasmodium falciparum in human blood was used in this study. The assay is based on DNA-DNA spot hybridization. For this purpose, the total genomic DNA of P. falciparum was isolated and purified from the parasite cultured in vitro. Then the total genomic DNA was used as a probe and labelled with [alpha-32P]-dATP by nick-translation. Twenty-five test samples, ten-microliter lysed infected blood each, were spotted onto dry nitrocellulose paper and hybridized with labelled genomic DNA. After hybridization, the paper was exposed to X-ray film for autoradiography, resulting in an image in places where hybridization occurred. The result shows that the assay appears to be sensitive enough to detect parasitaemia up to 0.0009%. No visible hybridization was detected in normal human blood or human leukocytes. Many samples can be processed simultaneously. This may be applicable to mass survey for detecting P. falciparum in epidemiological study (Fig. 2).
Rats intraperitoneally injected with a daily dose of cupric nitrilotriacetate (Cu-NTA), which contained 4 to 7 mg of copper/kg body weight, showed submassive liver necrosis, hemolytic anemia, and acute renal tubular necrosis at the beginning of the experiment and intermittently after 4 weeks of injections. All rats that survived over 8 weeks exhibited liver fibrosis with portal-portal, portal-central, and central-central bridging. In all rats that survived over 16 weeks, micronodular cirrhosis of the liver or extensive liver fibrosis was observed. The copper content of the cirrhotic/fibrotic liver was above 250 micrograms/g dry weight. Electron-microscopic x-ray analysis at day 93 revealed that copper stored in secondary lysosomes was always accompanied by a proportional amount of sulfur (correlation coefficient, 0.98; P less than 0.005). An experimental model of copper toxicosis in terms of copper-induced cirrhosis of the liver was established with exogenous copper chelated by nitrilotriacetate.
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A mycotoxin was extracted and purified from a strain of Fusarium moniliforme var. subglutinans isolated from mouldy corn seeds harvested in a serious Keshan disease region in Shaanxi Province. The purification procedure involves water extraction, ion exchange chromatography, desalination and crystallization. Its UV spectrum, IR spectrum and NMR are identical with that of the moniliformin. The toxin is highly toxic to young Beijing ducklings. The electrocardiogram (ECG) of the duckling was changed immediately after feeding with moniliformin. The cardiac muscle cells of Beijing ducklings were injured by the toxin. Toxicity may be alleviated to certain extent by applying adequate dosage of Selenium (3.18 X 10(-10) mol/L of H2SeO4) prior to moniliformin treatment. The permeability of the cardic muscle cells of the rats and young ducklings was damaged posterior to the injection of the toxin as tested by extracellular marcromolecular tracer (HRP) method. The relationship between moniliformin and Keshan disease was discussed. We consider that the moniliformin may be the causal agent of the disease.
Ricin A chain-containing immunotoxins (IT-As) specific for the human B-cell antigen, CD22, were prepared from 4 monoclonal antibodies (MAbs) or their Fab' fragments: RFB4, HD6, UV22-I and UV22-2. The ITs were tested for their ability to kill cells from the Burkitt lymphoma line, Daudi, the pre-B-cell leukemia line, NALM-6, and the myeloma cell line, ARH-77. Daudi expresses high levels of CD22, whereas NALM-6 and ARH-77 express low levels of CD22. The IgG-RFB4-A was highly toxic to all 3 cell lines; it killed 50% of the Daudi cells at a concentration of 1.2 x 10(-12) M and 50% of NALM-6 and ARH-77 cells at concentrations of 1.5 to 2.1 x 10(-11) M. IgG-RFB4-A was 10-30 times more toxic to Daudi cells than were the IgG-As constructed from the other 3 CD22 MAbs and 10 times more toxic than ricin itself. IT-As constructed from the Fab' fragments of the 4 CD22 antibodies were 2 to 5 times less toxic to Daudi cells than their IgG-A counterparts. Fab'-RFB4-A was twice as toxic to Daudi cells as ricin, whereas the other Fab'-As were about 7 times less toxic than ricin. Scatchard analyses of the binding of the radio-iodinated antibodies to Daudi cells showed that the intact RFB4 antibody bound 3-10 times more strongly than the other antibodies, whereas the Fab'-RFB4 bound 1.2 to 3.5 times more strongly than the Fab' fragments prepared from the other antibodies. Thus, the potent cytotoxic activity of the RFB4-As appears to derive, in part, from their superior binding affinity. Prior studies have shown that UV22-I and HD6 cross-react with certain normal human tissues lacking cells of B-cell lineage, whereas UV22-2 and RFB4 are B-cell-specific. This fact, together with its superior potency as an IT-A, suggests that RFB4 is the antibody of choice for preparing Fab'-As or IgG-As for in vivo therapy of human B-cell leukemias and lymphomas.
Since male A/J mice are much more susceptible to both acute and subacute nephrotoxicity and the carcinogenic effect of ferric nitrilotriacetate than female mice, sex differences in the lipid peroxidation level after ferric nitrilotriacetate use were examined. The effects of orchiectomy and testosterone were also investigated. Male and female A/J mice were given a single intraperitoneal injection of ferric nitrilotriacetate (3 mg of iron/kg of body weight) and then thiobarbituric acid reactivity was determined in the liver and the kidney. Only male mice showed high thiobarbituric acid reactivity after 30 min, with the kidney showing higher activity than the liver. Castrated male mice showed a reduction in thiobarbituric acid reactivity, whereas testosterone-pretreated castrated male or testosterone-pretreated female mice showed increased thiobarbituric acid reactivity. In addition, daily intraperitoneal injections of ferric nitrilotriacetate resulted in the death of all normal male mice within 6 days, whereas all female and castrated male mice survived 3 months of treatment. Thus, male and female mice showed differences in ferric nitrilotriacetate-induced toxicity as reflected in the degree of lipid peroxidation and mortality.
The effect of dietary vitamin E on renal tissue damage and lipid peroxidation was investigated following treatment with ferric nitrilotriacetate (Fe-NTA) in rats. Almost 100% renal proximal tubular necrosis was observed in the vitamin E-deficient rats following Fe-NTA treatment (5 mgFe/kg body wt, ip) as early as 12 hr. In the vitamin E-supplemented rats, no injury was observed in the proximal convoluted (cortical) tubules, although some injury was seen in the medullary outer stripe (mostly pars recta of the proximal tubules) 24 hr after Fe-NTA treatment. The tissue lipid peroxidation was dose-dependently increased 1 hr after a single ip injection of Fe-NTA (1 to 10 mg Fe/kg body wt). Vitamin E-deficient animals had an increased tissue content of thiobarbituric acid-reactive substance following Fe-NTA treatment, whereas vitamin E-supplemented animals showed suppressed lipid peroxidation. This study indicates that vitamin E provides some protection against the nephrotoxicity and associated lipid peroxidation induced by Fe-NTA.
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Iron and aluminum complexes of nitrilotriacetic acid cause severe nephrotoxicity in Wistar rats. In addition, a high incidence of renal cell carcinoma is seen in ferric nitrilotriacetate-treated animals. The present study was performed to see if lipid peroxidation is involved in ferric nitrilotriacetate toxicity. Ferric nitrilotriacetate had more bleomycin-detectable 'free' iron than any ferric salt, while iron complexed with desferrioxamine or ferric chondroitin sulfate had none. The toxicity of ferric nitrilotriacetate in vivo was more pronounced in vitamin E-deficient rats. A thiobarbituric acid-reactive substance was present in the kidneys of vitamin E-deficient rats in amounts markedly elevated compared to vitamin E-sufficient, or vitamin E-supplemented rats. Non-complexed nitrilotriacetate or aluminum nitrilotriacetate did not produce any thiobarbituric acid-reactive substance in vitamin E-sufficient rats died by the 58th day of administration. We suggest that the iron-stimulated production of free radicals leading to lipid peroxidation is the major cause of ferric nitrilotriacetate-mediated renal toxicity. Vitamin E, a known scavenger of free radicals, is effective in protecting against this iron-induced toxicity.
We investigated the induction of renal tumors by the ferric complex of nitrilotriacetic acid (Fe-NTA) in male and female A/J mice. Fifty-three male and 21 female mice received i.p. injections of Fe-NTA, 1.8 to 2.7 mg of iron/kg of body weight/day, 6 days a wk for 12 wk, at the longest. Ten male and ten female mice received nitrilotriacetic acid (NTA) i.p. at the dose equivalent to the NTA portion of Fe-NTA for the same period of time. Twenty male and 20 female mice left untreated served as the controls. Twenty-eight of the 53 Fe-NTA-treated male mice died within 14 days of the treatment. Renal proximal tubular cell necrosis was the major autopsy finding in these mice. On the other hand, all the Fe-NTA-treated female mice and NTA-treated male and female mice survived the 12 wk of treatment. Renal tubular cell carcinoma had developed in 15 of the 25 male mice and in one of the 21 female mice by the 420th day after the start of the experiment. The NTA-treated and control mice did not develop any tumors. In conclusion there is no species specificity in rats or mice in the induction of the renal carcinoma by Fe-NTA, but male mice are far more susceptible to both the acute or subacute toxicity and carcinogenic effect of Fe-NTA than are female mice.
A range of monoclonal antibodies specific for Plasmodium falciparum were tested in vitro for their abilities to inhibit the multiplication of a partially synchronized culture of P. falciparum, to augment the phagocytosis of the parasites by macrophages, and to enhance the killing of parasites by peritoneal cells depleted of adherent cells. Seven of 17 monoclonal antibodies, ranging from culture supernatant fluid and ascitic fluid to purified IgG, showed dose- and time-dependent inhibition of parasite growth in vitro. At a concentration of 0.6 mg/ml, the inhibitory capacity of these monoclonal IgGs was above 94% over a 3-day culture period, much higher than that of the relevant polyclonal IgG. Four of 6 monoclonal antibodies tested augmented the phagocytosis of the parasites by macrophages, which occurred as a result of opsonization of the parasites. Four of 7 monoclonal antibodies examined showed cytotoxic activity on malaria parasites. Peritoneal cells depleted of adherent cells were capable of killing the parasites in the presence of monoclonal antibodies. These results indicate that there may be 'monofunction', 'bifunction', and 'multifunction' types of monoclonal antibodies against P. falciparum. The putative protective antigen of malaria parasites purified by 'multifunctional monoclonal antibody' affinity chromatography may have potential interest as a vaccine against the parasite or as an immunodiagnostic reagent for human malaria.
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