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Biomedical subjects

H J Cheng

Publications and source records attributed to H J Cheng.

28 records · Page 2Linked to original sources

Identification and cloning of ELF-1, a developmentally expressed ligand for the Mek4 and Sek receptor tyrosine kinases.

Mek4 and Sek are tyrosine kinases with expression patterns in the mouse embryo that suggest important functions in early development. However, like all Eph family kinases, both were identified as orphan receptors without known ligands. We show that Mek4 and Sek soluble receptor-alkaline phosphatase fusion proteins can be used in a procedure termed RAP in situ to identify regions of ligand expression in the mouse embryo. Based on this spatial information, a cDNA expression library was prepared, and was screened with the fusion proteins to identify Eph ligand family-1 (ELF-1). In cell lines and embryos, ELF-1 is membrane bound by a phosphatidylinositol tail, a feature that may account for unique biological functions. Its sequence is homologous with B61, a ligand for the Eck kinase, defining a family of related ligands. The expression domains of ELF-1, Mek4 and Sek indicate potential roles in embryonic patterning.

Amino Acid Sequence↗

Transmembrane kit ligand cleavage does not require a signal in the cytoplasmic domain and occurs at a site dependent on spacing from the membrane.

The kit ligand (KL) is one of several growth factors that are active as transmembrane molecules and can also be proteolytically cleaved to yield soluble forms. We have investigated the signals and structural determinants that control the cleavage of KL. Presentation at the membrane appears to be critical, because no cleavage occurs in variants that lack a transmembrane domain. Signals in the cytoplasmic domain do not seem to be required, because cleavage was not blocked by removal of the C-terminal valine residue, deletion of the whole cytoplasmic tail, or the replacement of the cytoplasmic tail that occurs in the Sl17H mutation. KL thus appears to differ from transforming growth factor-alpha, which apparently requires a C-terminal valine as a signal for cleavage. Although proteolysis must be tightly restricted to the correct cell surface proteins and sites within each protein, cleavage of KL does not seem to be determined entirely by a requirement for a specific substrate sequence. However, the effects of deletion or insertion variants of KL suggest that cleavage may be limited to sites within a specific range of distances from the cell membrane.

Amino Acid Sequence↗

Identification of the types of adenovirus isolates with monoclonal antibodies.

The types of 59 isolates of adenovirus (Adv) which were isolated between winter, 1984 and spring, 1986 were identified by type-specific monoclonal antibodies (McAb) against Adv types 3 and 7. The results showed that the method could not only identify the types of Adv, but also discover the changes of their subtypes with time. The tedious neutralization test can be replaced by this simple method.

Adenoviruses, Human↗

Manufacture and clinical employment of an antibiotic silicon-rubber catheter.

In order to present or minimize the frequent occurrence of urinary infection and other complications following indwelling catheterization, we devised a drug-releasing silicon catheter. Attached to its tip is an appliance which has a honeycomb pattern with many spaces into which antibiotic particles are inserted. In our series, 28 patients suffering from various conditions were treated accordingly with very gratifying results. Kanamycin is found to be the antibiotic of choice which can be slowly but constantly released when coming into contact with the urine. Following treatment the concentration of kanamycin in urine could be maintained at a level of 25-100 micrograms/ml of urine for a period of 20-24 days, much higher than the therapeutic value of 20 micrograms/ml of urine.

Female↗

Two-balloon and four-channel silicone rubber catheter for drug injection in the treatment of chronic bacterial prostatitis.

A new type of silicone rubber catheter with two balloons and four channels is introduced for the treatment of chronic bacterial prostatitis. Through this specially conceived catheter, a drug can be instilled in the posterior urethra, the two balloons blocking the drug from passing either into the bladder or the membranous urethra. Treatment has been applied in 212 cases of chronic bacterial prostatitis with very good results.

Adult↗

An epidemiological study on the effect of N, N'-methylene-bis-(2-amino-1,3,4-thiadiazole) (MATDA) on outcomes of pregnancy.

A retrospective cohort study on the effect of the suspected teratogenic pesticide N, N'-methylene-bis-(2-amino-1,3,4-thiadiazole) (MATDA) on outcomes of pregnancy was conducted. The exposed group (6,173 pregnancies) was composed of childbearing women who, during their gestation, consumed rice harvested from a field where MATDA had been applied. The control I group (10,145) came from an adjacent county where MATDA had never been used; the control II group (3,326) consisted of women who had been pregnant previous to the introduction of this pesticide in the same region as the exposed group. The validity of the survey was verified by comparability and data-checking studies. After adjustment for the calendar year, maternal age, and pregnancy order, no significant differences were found in rates of spontaneous abortion, fetal death and stillbirth, birth defects, as well as in sex ratio and birth weight between the study groups. The same result was found in the comparison of individual categories of malformation. The rates of the birth defects were 23.84, 21.49, and 22.78 per 1,000 live births for the exposed, internal, and external control groups, respectively. No dose-response relationship was revealed. The results were consistent with previous reports and indicated the difference between animal experiments and human exposures. Although MATDA is teratogenic in animals, it is clear that the pesticide does not adversely effect outcomes of pregnancy in humans as currently applied.

Abortion, Spontaneous↗

Macromolecular transport across arterial and venous endothelium in rats. Studies with Evans blue-albumin and horseradish peroxidase.

Atherosclerotic lesions are characterized by lipid infiltration in regions with high rates of endothelial cell turnover. The present investigation was designed to elucidate the route of macromolecular transport across vascular endothelium. The aorta and vena cava of male Sprague-Dawley rats were perfusion-fixed after the intravenous injection of Evans-blue albumin (EBA) or horseradish peroxidase (HRP). Fluorescence microscopic examination of en face preparation of the aorta stained with hematoxylin allowed the identification of endothelial cells that underwent mitosis, together with the localization and quantification of fluorescent spots for EBA leakage. The HRP specimens were subjected to histochemical treatment, and HRP leakage was seen as brown spots under the light microscope. Silver nitrate stain was added in both EBA and HRP studies to outline cell boundaries and to visualize stigmata, stomata, and dead cells. In the aorta, almost every dividing cell showed junctional leakage to albumin and HRP, with clustering of leaky spots around the branch orifices. Time-dependent studies showed gradual increases in the diameter and number of these heterogeneously sized leaky spots, which finally fused to sizes corresponding to the "blue areas" for EBA or "brown areas" for HRP. Compared with arteries, veins had fewer mitotic cells, but more dead cells and diffuse dye-staining areas, indicating a more rapid transport of macromolecules. The leaky spots in the artery were associated mainly with mitotic cells, dead cells, and stigmata, whereas those in the vein occurred primarily at regions with dead cells. These results suggest that the preferential association of the enhanced transport of macromolecules with mitosis in the arterial as compared to venous endothelium and the differential behavior in transmural transport between arteries and veins may form the basis for the predilection of atherosclerosis in arteries.

Animals↗