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Biomedical subjects

B Q Li

Publications and source records attributed to B Q Li.

7 recordsLinked to original sources

Nerve growth factor stimulation of the Ras-guanine nucleotide exchange factor and GAP activities.

The biological activity of Ras proteins is thought to be controlled by the guanine nucleotide exchange factor and the guanosine triphosphatase activating protein (GAP). Treatment of rat pheochromocytoma PC-12 cells with nerve growth factor (NGF) increased the amount of active Ras guanosine triphosphate complex and stimulated the activities of both the guanine nucleotide exchange factor and GAP. In PC-12 cells that overexpressed the tyrosine kinase encoded by the trk proto-oncogene (a component of the high-affinity NGF receptor), the NGF-induced activation of the regulatory proteins was potentiated. These results suggest that the NGF receptor system enhances the activities of both the guanine nucleotide exchange factor and GAP and that the activation of Ras might be controlled by the balance in activity between these two regulatory proteins.

Animals

A new class of anti-HIV agents: GAP31, DAPs 30 and 32.

Three inhibitors of human immunodeficiency virus (HIV) have been isolated and purified to homogeneity from Euphorbiaceae himalaya seeds (Gelonium multiflorum) and carnation leaves (Dianthus caryophyllus). These proteins, GAP 31 (Gelonium Anti-HIV Protein 31 kDa) and DAPs 30 and 32 (dianthus anti-HIV proteins, 30 and 32 kDa), inhibit HIV-1 infection and replication in a dose-dependent manner with little toxicity to target cells. The therapeutic indices of these compounds are in the order 10(4), suggesting that they may be clinically important agents in the treatment of AIDS. The N-terminal amino acid sequences of these proteins show little homology to those of previously described anti-HIV proteins. The structure-function features of these HIV inhibitors, based on the 40-60 amino acid residues of N-terminal sequences, are examined.

Amino Acid Sequence

TAP 29: an anti-human immunodeficiency virus protein from Trichosanthes kirilowii that is nontoxic to intact cells.

An anti-human immunodeficiency virus (anti-HIV) protein capable of inhibiting HIV-1 infection and replication has been isolated and purified to homogeneity from Trichosanthes kirilowii. This protein, TAP 29 (Trichosanthes anti-HIV protein, 29 kDa), is distinct from trichosanthin [also known as GLQ 223 (26 kDa)] in size, N-terminal amino acid sequence, and cytotoxicity. In addition to three conservative substitutions--namely, Arg-29 to Lys, Ile-37 to Val, and Pro-42 to Ser--a total difference of residues 12-16 was found. TAP 29 yielded -Lys-Lys-Lys-Val-Tyr-, whereas trichosanthin has -Ser-Ser-Tyr-Gly-Val-. Although the two proteins exhibit similar anti-HIV activity, as measured by syncytium formation, p24 expression, and HIV reverse transcriptase activity, they differ significantly in cytotoxicity, as measured by their effects on cellular DNA and protein syntheses. At the dose level of the bioassays, 0.34-340 nM, trichosanthin demonstrates a dose-dependent toxic effect on host cells. TAP 29 displays no toxic effect, even at 100 X ID50, whereas trichosanthin demonstrates 38% and 44% inhibition on cellular DNA and protein synthesis, respectively. These results indicate that the therapeutic index of TAP 29 is at least two orders of magnitude higher than that of trichosanthin. Thus TAP 29 may offer a broader safe dose range in the treatment of AIDS.

Amino Acid Sequence

Decrease in cytokine production by HIV-infected macrophages in response to LPS-mediated activation.

The capacity of human monocytes/macrophages (M/M) infected with a human immunodeficiency virus-1 (HIV-1) isolate to produce several immunomodulating cytokines including interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8, and macrophage chemoattractant and activating factor (MCAF) was examined. Although HIV infection itself induced significant increases in the level of mRNAs for IL-1 beta, TNF-alpha, IL-6, and IL-8, the levels of lipopolysaccharide (LPS)-induced mRNAs for IL-1 alpha, IL-1 beta, TNF-alpha, IL-6, IL-8, and MCAF were decreased over those of uninfected LPS-stimulated cells. In addition, HIV-infected M/M produced lower amounts of IL-8 protein, as measured by radioimmunoassay over an 18-day culture period. These results suggest that HIV infection generally suppresses the LPS-inducible cytokine production in human M/M. The impact of the role of these cytokines in the immunity and pathogenesis of HIV-1 infection is discussed.

Acquired Immunodeficiency Syndrome

[Multicentric carcinoma of the esophagus and double primary malignant neoplasm of the upper alimentary tract--report on 44 patients].

During the past fifteen years, 44 patients with multicentric carcinoma of the esophagus or double primary malignant neoplasm of the upper alimentary tract, collected from 5316 patients with cancer of esophagus or gastric cardia in the same period, were treated in our hospital. The incidence was 0.83%. All were proven by pathology. Exploratory thoracotomy was done in 32 patients and 26 lesions were resected with a resection rate of 81.3%. All patients with cancer resected survived over 1 year, 6 out of 9 survived over 3 years and 2 out of 3, over 5 years. In the 18 patients who received chemotherapy alone, 12 were followed and all died within 1 year. It is shown that multicentric carcinoma of the esophagus or double malignant neoplasm of the upper alimentary tract should be given energetic treatment. Finally, the incidence, diagnosis criteria, diagnosis method, etiology and management are discussed with a review of literature.

Adenocarcinoma