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Biomedical subjects

R Zhang

Publications and source records attributed to R Zhang.

At least 523 records · Page 29Linked to original sources

Genetic regulation of mammary carcinogenesis in the rat by susceptibility and suppressor genes.

Rat strains differ in their susceptibilities to mammary carcinogenesis. Strains such as Wistar-Furth are very susceptible to chemically induced carcinogenesis. This phenotype is controlled by autosomally dominant susceptibility genes. Strains such as the Copenhagen are resistant to spontaneous and induced mammary carcinogenesis. This phenotype is controlled by an autosomal dominant gene termed the mammary carcinoma suppressor (MCS). Strains with intermediate susceptibility such as the F344 carry neither the MCS nor susceptibility genes. Both the MCS and susceptibility genes are chiefly active within the mammary parenchyma. Both genes act at carcinogenesis stages beyond carcinogen metabolism and DNA adduction. The MCS gene completely inhibits both palpable and microcarcinomas. It does not inhibit focal alveolar hyperplasias. Its gene product acts solely within the mammary epithelial cell in which it is produced. We are currently investigating the interactions of various oncogenes and the MCS gene. In addition, efforts are underway to identify and clone this gene.

9,10-Dimethyl-1,2-benzanthracene↗

Purification and primary structure of C-1027-AG, a selective antagonist of antitumor antibiotic C-1027, from Streptomyces globisporus.

C-1027-AG, a selective antagonist of antitumor antibiotic C-1027, was isolated by column chromatography on DEAE-cellulose, butyl-Toyopearl and Sephadex G-50 from a culture filtrate of Streptomyces globisporus. The amino acid sequence of purified C-1027-AG was determined with a protein sequencer on the basis of fragment peptides obtained by enzymatic hydrolysis with lysylendopeptidase, V8 protease, endopeptidase AspN and chymotrypsin, after performic acid oxidation. C-1027-AG is shown to consist of a single polypeptide chain cross-linked by two disulfide bonds, and to contain a total of 110 amino acid residues with alanine and glycine as its amino- and carboxyl-termini, respectively; its molecular weight was calculated to be 10,500 daltons. The primary structure of C-1027-AG is indicated to be identical to the protein moiety of C-1027, and is highly homologous to the sequences of antitumor proteins obtained from other Streptomyces species.

Amino Acid Sequence↗

Serum-free culture system for L-CFU assay on acute non-lymphocytic leukemia cases.

A completely serum-free culture system for L-CFU assay in vitro on 5 cases of acute non-lymphocytic leukemia (ANLL) is reported. Several agents were tested for the requirement of L-CFU assay in order to substitute the animal or human serum in the conventional culture medium. The results showed that fraction V of bovine serum albumin (2 x 10(-4) mol/L), iron saturated human transferrin (400 micrograms/ml), insulin (1 U/ml), and cholesterol (20 micrograms/ml) were indispensible components for the growth of ANLL L-CFU. Colonies of larger size could be obtained by adding 2-mercaptoethanol. HTB9-CM as the source of growth stimulating factor was used in all experiments. This method is useful for the study of L-CFU proliferation regulated by the human hemopoietic growth factors and the standardization of L-CFU assay.

Adult↗

[Studies on assessment of intensity of infection of Schistosoma japonicum in cattle].

In order to carry out quantitative epidemiological survey of animal schistosomiasis, a sensitive egg-counting method was studied both in the laboratory and in the field. Fecal material was filtered by a copper gauze (60 meshes/inch) into a nylon-tissue bag with 2 layers, 150 and 260 meshes/inch respectively. Thin smears were made from the residue in the bag. The mean recovery rate of mature schistosome eggs by previously adding 100 eggs to 5g of feces from noninfected cattle was 67.5%, ranging from 53 to 81%. To compare the egg-concentration thin smear method mentioned above, with egg-concentration thick smear method after hyalinization, various numbers of eggs, namely, 25, 50 and 100, were added to 5g of feces. The mean recovery rates of fecal eggs were 57.6%, 57.6% and 69.1% respectively, for the thin smear method and 3.2%, 13.8% and 19.5% for the thick smear method. The coefficients of variability in the former were from 12.9% to 17.4% and in the latter, from 30.7% to 98.8%. The total number of schistosome eggs per 5g of feces found in 34 egg-positive cattle in the field were 434 and 178 by the thin smear method and the thick smear method, respectively. A correlation analysis performed on the numbers of detected eggs in a total volume of fecal sediment and from half a volume of fecal sediment multiplied by two, showed a correlation coefficient of 0.98 (P less than 0.01), indicating that half a volume of fecal sediment may be used instead of a whole volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Effects of stimulating periaqueductal gray on the nociceptive neuron discharges of post-thalamic nucleus evoked by stimulation of splanchnic nerve in cats].

The effects of stimulating periaqueductal gray (PAG) on the nociceptive neuron discharges of pronucleus evoked by stimulating the splanchnic nerve in cats were studied. The two kinds of inhibitory action were observed. One was called early phase or prompt inhibition phase which occurred within 30 ms to 150 ms after stimulation of PAG. The other was called slow-pase or sustained inhibition which occurred from a few minutes to more than ten minutes after the stimulation of PAG. The results showed that PAG played an important role in the analgesia of visceral pain. Both kinds of inhibition may be blocked by naloxone, this suggests that endogenous opiate like substances involved in these inhibitory processes caused by stimulating role in the inhibitory effect of PAG.

Animals↗

[The role of midbrain periaqueductal grey in the inhibition of central cardiac ischemia by somatic nerve and its mechanism in rabbits].

UNLABELLED: Experiments were performed on vagotomized male rabbits weighing 1.8-2.2 kg. Urethane and chloralose were administered intravenously, and were paralyzed by flaxedil. After a cannula was inserted into femoral artery to measure blood pressure, the epicardial electrogram (EECG) was recorded. Then we inserted a bipolar electrode into caudal dorsolateral subdivision of periaqueductal grey (CDL), or dorsomedial hypothalamic nucleus (DMH). In some animals, a microinjecting tube was inserted into CDL for microinjection of enkephalin antibodies. In 12 animals, stimulation of CDL could elicit pressor response and elevation of EECG-ST segment. When stimulating deep peroneal nerve, these two responses were inhibited. In 14 animals, with brainstem transected in P5 level, the stimulation of DPN could not inhibit the presser response induced by CDL, but still inhibited the EECG-ST segment changes. After enkephalin antibodies were injected into CDL, DPN could not inhibited EECG-ST changes. In 4 animals, instead of enkephalin antibodies, rabbit serum had no effects. The unit discharges of 96 neurons in CDL were recorded by glass microelectrodes, among them, 15 neurons could be excited by DMH stimulation. We called these neurons the defence reaction related neurons. Stimulation of DPN or median nerve could inhibit the spontaneous discharge and DMH evoked discharge of these defence reaction related neurons. CONCLUSIONS: 1. DPN stimulation can inhibit the pressor response and cardiac ischemia induced by defence reaction centre in CDL of PAG. The inhibitory effect on cardiac ischemia is still eminently remained after the brainstem is cut in P5 level to eliminate the influence of hypothalamic arcuate nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Suppressive effect of high energy shock waves on tumor cells.

Suppressive effect on tumor cells of high energy shock waves (HESW) has aroused the interest of physicians in recent years. We assessed experimentally the cytotoxic effects of HESW on tumor cells both in vitro and in vivo and determined whether a Chinese domestic lithotriptor is capable of generating effective HESW, which has the potential to break tumor cells, reduce cell viability, retard cell growth, delay doubling time, impair cell attachment and cell clonogenicity. In nude rats, HESW was able to delay tumor growth and reduce tumor size without evidence of metastasis. The nature of HESW in the induction of cell damage and its clinical application need to be further investigated.

Animals↗

[Toxic principles of Oxytropis glabra DC].

Eight alkaloids were isolated from Oxytropis glabra and identified as anagirine, thermopsine, N-methylcytisine, sparteine, baptifoline, adenine, dictamnine and ethyl allophanate respectively by spectral analysis and physicochemical methods. All these alkaloids were isolated from this genus for the first time and ethyl allophanate was found in nature for the first time.

Alkaloids↗

Evidence of paired M2 muscarinic receptors.

Binding assays involving various antagonists, including N-[3H] methylscopolamine, [3H]quinuclidinyl benzilate, AFDX-116, pirenzepine, and propylbenzilylcholine mustard, disclosed only a single population of M2 muscarinic receptors in membranes from the rat "brainstem" (medulla, pons, and colliculi). However, competition curves between N-[3H]methylscopolamine and various agonists, including oxotremorine, cis-dioxolane, and acetylethylcholine mustard, showed approximately equal numbers of guanine nucleotide-sensitive high affinity (H) sites and guanine nucleotide-insensitive low affinity (L) sites. This 50% H phenomenon persisted in different buffers, at different temperatures, after the number of receptors was halved (and, thus, the remaining receptor to guanine nucleotide-binding protein ratio was doubled), after membrane solubilization with digitonin, and when rabbit cardiac membranes were used instead of rat brainstem membranes. Preferential occupation of H sites with acetylethylcholine mustard, and of L sites with quinuclidinyl benzilate or either mustard, yielded residual free receptor populations showing predominantly L and H sites, respectively. Low concentrations of [3H]-oxotremorine-M labeled only H sites, and the Bmax for these sites was 49% of the Bmax found with [3H]quinuclidinyl benzilate plus guanine nucleotide. These and other results are most consistent with the idea that H and L receptor sites exist on separate but dimeric receptor molecules and with the hypothesis that only the H receptors cycle between high and low affinity, depending upon interactions between this receptor molecule and a guanine nucleotide-binding protein.

Animals↗

Quantitating the frequency of initiation and cH-ras mutation in in situ N-methyl-N-nitrosourea-exposed rat mammary gland.

Mammary carcinogenesis is a multistep process consisting minimally of initiation and promotion/progression stages. The rate-limiting stage in the carcinogenesis process is undetermined but can in part be addressed by estimating the frequency of initiation, a heritable early event. Here, we use an in vivo limiting dilution transplantation assay to estimate initiation frequency in a rat mammary epithelial stem-like cell population that was exposed in situ to 50 mg/kg N-methyl-N-nitrosourea (NMU) administered i.v. We estimate that this dose resulted in the killing of 65% of exposed mammary cells. Known numbers of cells surviving NMU exposure were grafted into fat-pads of recipient rats in which the cells grew and differentiated into structurally and functionally normal mammary glands. Recipient rats were hormonally manipulated to provide maximal promotion of initiated cells. Mammary carcinomas developing at graft sites were quantitated over a 2-year period. Based on these results, we estimate that at least 1 surviving NMU-exposed mammary cell in 7,200 was initiated. Seventeen % of these graft site carcinomas had an activated H-ras oncogene with a G to A mutation in codon 12. This suggests that at least 1 mammary cell in 43,000 was mutated in this fashion by in situ exposure to NMU. These data suggest that cH-ras represents approximately 1 of 5 of the initiation events produced by NMU exposure of rat mammary glands.

Animals↗

[Experimental study on cricoarytenoid joint movement].

Through the study on 80 sides of the cricoarytenoid joints, it was proved that the cricoarytenoid joint was a small joint having multiple forms of movements. As the glottis opened or closed the arytenoid cartilage would slide first along the major axis of the joint facet, then round the inclined axle complemented by transverse and perpendicular movements round the joint facet. The closing movements of the glottis took place at the anterior part of the joints while the opening movements at the posterior part of the joints. The vocal process would move outwards and inwards as the arytenoid cartilage slided along the direction of the major axis of the joint facet.

Animals↗

[A survey on polio paralysis in Shandong Province Department of Program Immunization, Cooperation Group on the Survey of Polio Paralysis].

The survey was conducted in four counties where Polio consistently occurred during 1986-1988. According to the survey, there were 251 polio cases from 1974 to 1989, of which only 138 cases were reported. The paralytic rate by polio in the population under 15 years old was 0.486%. The survey also showed that polio was still a severe disease which paralysed children in the country. The number of polio cases accounted for 48% of all paralytic persons. Legs were the chiefly affected limbs, being about 90%. From analysis of vaccine history of polio cases, we found that the difference between two groups was highly significant. 90% of polio cases had no vaccine history or no full vaccine history. The reason for this was mainly due to lack of related knowledge. In addition, we also analysed multiple birth factor, which seemed to be not significant.

Adolescent↗

Reduction in the frequency of activated ras oncogenes in rat mammary carcinomas with increasing N-methyl-N-nitrosourea doses or increasing prolactin levels.

The role of c-Ha-ras-1 oncogene activation in the multistage biological process of N-methyl-N-nitrosourea (NMU)-induced mammary carcinogenesis was investigated. The average yield of NMU-induced mammary tumors in Wistar-Furth rats was altered by modification of either the initiation or promotion/progression stage of carcinogenesis. Initiation was varied by the use of different doses of NMU from 20 to 50 mg/kg. Tumor yield was increased with increasing NMU doses. However, the frequency of mammary tumors with activated c-Ha-ras-1 decreased in a linear fashion with increasing NMU doses. Promotion/progression was varied by increasing prolactin levels starting approximately 2 weeks after NMU administration. This hormonal manipulation increased tumor yield, while reducing the frequency of tumors with activated ras. It is postulated that ras activation represents one of several possible mechanisms by which NMU initiates mammary carcinogenesis. Furthermore, initiated cells without activated ras are more dependent on epigenetic promotional events provided by either prolactin or NMU than are ras-initiated cells.

Adrenalectomy↗

Relationship of a putative receptor protein kinase from maize to the S-locus glycoproteins of Brassica.

The protein kinase family of enzymes mediates the responses of eukaryotic cells to both inter- and intracellular signals. These enzymes are either serine/threonine-specific or tyrosine-specific. Many of the latter are transmembrane receptors and are important in transduction of extracellular signals across the plasma membrane, whereas few examples of receptor serine kinases have been reported. We have now identified a complementary DNA clone from Zea mays (L.) encoding a putative serine/threonine-specific protein kinase structurally related to the receptor tyrosine kinases. This structural similarity is evidence for a previously undescribed class of transmembrane receptor in higher plants likely to be involved in signal reception and transduction. Furthermore, the catalytic domain of this protein kinase is linked through a transmembrane domain to an extracellular domain similar to that of glycoproteins encoded in the self-incompatibility locus of Brassica which are involved in the self-recognition system between pollen and stigma.

Amino Acid Sequence↗

Isolation and characterization of two novel rat ovarian lactogen receptor cDNA species.

Two novel lactogen receptor cDNA clones (2.1 and 1.2 kb) were isolated from a rat ovarian cDNA library. Nucleotide sequence of the 2.1 kb clone codes for a 610 aa receptor (nonglycosylated mol. wgt. 66,000 D) with an extracellular domain, a transmembrane region and an intracellular domain, and exhibited significant overall similarity with the rat liver receptor (310 aa) and both rabbit mammary and human hepatoma receptors (616 and 622 aa). However, the ovarian lactogen receptor sequence contains a unique cytoplasmic domain of 110 aa and consensus sequences for both a tyrosine phosphorylation site and an ATP/GTP type A binding site, and thus has potential for signal transduction and mitogenic activity. The 1.2 kb clone codes for a truncated binding form of 150 aa that is identical with the ovarian long form over only the first 130 residues, and lacks the transmembrane region. Differences between long and short forms of the ovarian lactogen receptors and the truncated liver species may result from alternative splicing. The prolactin holoreceptor gene(s) has the potential for producing several receptor subtypes that differ in tissue-specific expression, size, compartmentalization and mode of signal transduction, and may subserve the divergent functions of prolactin in its several target cells.

Amino Acid Sequence↗

Purified N-cadherin is a potent substrate for the rapid induction of neurite outgrowth.

N-cadherin is the predominant mediator of calcium-dependent adhesion in the nervous system (Takeichi, M. 1988. Development (Camb.). 102: 639-655). Investigations using antibodies to block N-cadherin function (Bixby, J.L., R.L. Pratt, J. Lilien, and L.F. Reichardt. 1987. Proc. Natl. Acad. Sci. USA. 84:2555-2569; Bixby, J.L., J. Lilien, and L.F. Reichardt. 1988. J. Cell Biol. 107:353-362; Tomaselli, K.J., K.N. Neugebauer, J.L. Bixby, J. Lilien, and L.F. Reichardt. 1988. Neuron. 1:33-43) or transfection of the N-cadherin gene into heterologous cell lines (Matsunaga, M., K. Hatta, A. Nagafuchi, and M. Takeichi. 1988. Nature (Lond.). 334:62-64) have provided evidence that N-cadherin, alone or in combination with other molecules, can participate in the induction of neurite extension. We have developed an affinity purification procedure for the isolation of whole N-cadherin from chick brain and have used the isolated protein as a substrate for neurite outgrowth. N-cadherin promotes the rapid extension of neurites from chick ciliary ganglion neurons, which extend few or no neurites on adhesive but noninducing substrates such as polylysine, tissue culture plastic, and collagens. N-cadherin is extremely potent, more so than the L1 adhesion molecule, and comparable to the extracellular matrix protein laminin. Compared to laminin, however. N-cadherin promotes outgrowth from ciliary ganglion neurons extremely rapidly and with a distinct morphology. These results provide a direct demonstration that N-cadherin is sufficient to induce neurite outgrowth when substrate bound and suggest that the mechanism(s) involved may differ from that induced by laminin.

Animals↗

Site of expression and biological function of the rat mammary carcinoma suppressor gene.

The rat mammary carcinoma suppressor (MCS) gene is an autosomal dominant gene found in the Copenhagen (Cop) rat that specifically prevents carcinogen-induced and spontaneous mammary carcinomas. Mammary cells from the Wistar-Furth (WF) rat, which do not carry the MCS gene, were grafted into ectopic sites in WF X Cop and WF X Fischer 344 hybrid rats. Only the former hybrid carried the MCS gene. These chimeric rats were then treated with 7,12-dimethylbenz[a]anthracene (DMBA) and the development of mammary carcinomas was followed. The results suggested that the main site of MCS activity was within the mammary parenchyma. However, a minor abscopal effect of this gene was also observed. Ectopic mixed mammary glands composed of a mixture of Cop and WF cells were also examined for susceptibility to DMBA-induced carcinogenesis. The presence of Cop cells did not inhibit tumor development from WF cells in these mixed glands. Finally, graft sites in which palpable tumors did not develop were examined for focal epithelial lesions. The MCS gene was found to inhibit completely the formation of microcarcinomas, but did not affect the development of alveolar hyperplasias.

9,10-Dimethyl-1,2-benzanthracene↗