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Biomedical subjects

C S Song

Publications and source records attributed to C S Song.

At least 55 records · Page 3Linked to original sources

Structure and regulation of the senescence marker protein 2 gene promoter.

The liver-specific expression of the senescence marker protein 2 (SMP-2) in the male rat is markedly reduced during the androgen-sensitive state of young adulthood, whereas it is up-regulated during the androgen-insensitive phases of prepuberty and senescence. Nuclear runoff studies show that the age-dependent changes in SMP-2 expression are due to transcriptional regulation of the gene. In order to explore the mechanism of the regulatory process, we have cloned the upstream flanking regions of two distinct SMP-2 genes (SMP-2A and SMP-2B) and established their nucleotide sequence. These clones contain approximately 2.2 kb of the 5'-flanking sequence, exons 1 and 2, the first intron, and a portion of the second intron. The SMP-2 genes, as well as the upstream sequences, contain the sequence motifs for a number of cis-acting regulatory elements, such as the hepatocyte-specific element (HP1) and the androgen response element (ARE). S1 nuclease and primer extension analyses have established the transcription initiation sites for these genes. For functional analysis of the upstream sequences, we have constructed a hybrid plasmid containing the SMP-2A gene sequence (-1970 to +38 bases) fused to the structural gene for chloramphenicol acetyl-transferase (CAT). Upon transfection into rat hepatoma cells (FT02B), this construct was able to drive expression of the CAT gene. The same construct, however, failed to function in fibroblast-derived L cells, indicating tissue-specific regulation of the construct promoter.

Animals↗

Loss of androgenic induction of alpha 2u-globulin gene family in the liver of NIH black rats.

Unlike all known strains of rat, the androgen-inducible alpha 2u-globulin gene family is totally silent in the liver of NIH black (NB) rats. No endocrinological or reproductive abnormalities are apparent, and the mRNA for the androgen-repressible hepatic protein SMP-2 is normally regulated in these animals. Furthermore, immunoblot analysis shows a normal level of the male-specific cytoplasmic androgen-binding protein. Cross-breeding of the NB male and Sprague-Dawley female shows that the hybrid male in the F-1 generation regains the androgen-dependent expression of alpha 2u-globulin in the liver. These results along with the observation of high constitutive level of alpha 2u-globulin mRNA in the preputial gland of NB rats indicate a tissue- and gene-specific regulatory defect which prevents androgenic induction of alpha 2u-globulin in the liver.

Alpha-Globulins↗

Cloning, sequencing, and regulation of rat liver carnitine octanoyltransferase: transcriptional stimulation of the enzyme during peroxisome proliferation.

Several complementary DNAs for the peroxisomal enzyme carnitine octanoyltransferase (COT), cloned in the expression vector lambda gt11, have been isolated. Together, these clones cover 2143 bp of the COT cDNA sequence with an open reading frame for 523 amino acids. Northern analysis showed the mRNA size for this enzyme to be 3.5 kilobases. The 523 residue long amino acid sequence amounts to a molecular mass of 60,269 daltons, indicating that the cloned cDNAs contain most or all of the coding sequence for COT (Mr approximately 62,000). Hybridization studies showed that the increased COT activity in the liver of rats, fed the potent peroxisome-proliferating drug Wy-14,643, is associated with a more than 40-fold rise in the steady-state level of the COT mRNA.

Acyltransferases↗

Pseudomonas aeruginosa cytotoxin stimulates secretion of amylase and protease zymogens with a concomitant decrease of mRNA levels in isolated rat pancreatic acini.

The action of Pseudomonas aeruginosa cytotoxin on isolated pancreatic acini was investigated. The release of amylase and serine protease zymogens from the isolated rat pancreatic acini was induced with increasing amounts of cytotoxin in vitro. The stimulated release of amylase reached 30% of total cellular content with 100 micrograms/mL of the purified cytotoxin. The induced release of amylase, trypsinogen, proelastase, and chymotrypsinogen reached the maximum after 75 minutes of incubation while lactate dehydrogenase began to appear after 15 minutes of incubation with a secondary biphasic increase at 75 min of incubation. The concentrations of acinar mRNAs of amylase, trypsinogen, proelastase, and chymotrypsinogen, as measured by dot-blot hybridization with the cloned cDNAs of amylase, trypsinogen I, proelastase II, and chymotrypsinogen B of the rat, decreased with time and were significantly lower than in the untreated acini. It is concluded that cytotoxin stimulates the release of amylase and protease zymogens with a concomitant increase in membrane permeability and a decrease of cellular mRNA levels. The inhibition of gene expression is attributable merely to a generalized toxic effect upon cellular metabolism.

Amylases↗

Computed tomography of cavernous sinus diseases.

We retrospectively analyzed CT scans of 21 cavernous sinus lesions in an attempt to discover CT findings helpful to the differential diagnosis. With the integration of various CT observations it was possible to categorize the lesions into inflammatory, vascular, benign neoplastic and malignant metastatic lesions with few exceptions. Four of 5 cases of septic cavernous sinus thrombophlebitis revealed unilateral or bilateral multiple irregular filling defects in the enhancing cavernous sinus with or without orbital inflammatory change. Four of 5 cases of carotid-cavernous fistula demonstrated unilateral or bilateral diffuse bulging and homogeneous enhancement of the cavernous sinus with obliteration of normal low densities of cranial nerves and gasserian ganglion. Dilatation and tortuosity of superior ophthalmic vein were also associated. Four of 5 cases of benign neoplastic lesion showed well-circumscribed enhancing masses confined to the cavernous sinus with pressure erosion or hyperostosis of adjacent bone. Five of 6 cases of malignant metastatic lesion showed changes suggesting malignancy such as destruction of adjacent bone or associated manifestations of intracranial spread. As compared with the axial scan, coronal scans proved to be more sensitive in detection of subtle cavernous sinus expansion, and superior in evaluation of intracavernous neural structures, relationships with the pituitary gland and changes in the skull base. Axial scans, however, were superior in detection of associated orbital and intracranial abnormalities. Scans in both projections are needed in the evaluation of most cavernous sinus diseases.

Arteriovenous Fistula↗

Antibodies to the alpha-subunit of insulin receptor from eggs of immunized hens.

Simple methods for the generation, purification, and assay of antibodies to the alpha-subunit of insulin receptor from eggs of immunized hens have been described. Chicken antibodies against the alpha-subunit inhibit insulin binding to the receptor and stimulate glucose oxidation as well as autophosphorylation of the beta-subunit. Thus the properties of chicken antibodies are very similar to those of antibodies found in human autoimmune diseases and different from rabbit antibodies obtained against the same antigen.

Adipose Tissue↗

Reevaluation of properties of acetyl-CoA carboxylase from rat liver.

Rat liver acetyl-CoA carboxylase can be rapidly isolated by a new procedure which uses avidin-Sepharose affinity chromatography. The isolated enzyme has Mr = 260,000; none or very little of the proteolytic products of the carboxylase which are formed in conventional purification procedures are found in our preparations. It is apparent that the previously reported subunit of the carboxylase, with Mr = 230,000, is itself the product of proteolysis. The properties of the enzyme produced by our new method are quite different from those of the conventionally prepared enzyme. Our enzyme contains 6 mol of alkali-labile phosphate/mol of subunit, rather than 2 mol; the Km for acetyl-CoA is about 8-fold higher and the specific activity is only about one-fifth of that previously reported. The large amount of phosphate does not appear to cause the low specific activity of the new enzyme preparation, because alkaline phosphatase treatment reduces the number of phosphates/subunit from 6 to 3 mol but does not change the specific activity.

Acetyl-CoA Carboxylase↗

Niacin Reduces Paraquat Toxicity in Rats.

Rats poisoned with paraquat benefited from daily niacin therapy. Niacin-treated rats showed delayed and reduced dyspnea. Deaths began approximately 30 hours later. The time required for niacin-treated rats to reach 50 percent mortality increased from 60 to 120 hours, and the dealth rate was reduced form 75 to 55 percent. The benefit by niacin is consistent with the demonstrated role of niacin in preventing cellular decreases of nicotinamide adenine dinucleotide during poisoning of bacteria by paraquat and by hyperbaric oxygen.

Animals↗

Coenzyme A activation of acetyl-CoA carboxylase.

Acetyl-CoA carboxylase is activated by physiological concentrations of CoA. Activation of partially purified enzyme by CoA is accompanied by a decrease in the Km for acetyl-CoA from 0.2 mM to about 4 microM, which is the physiological concentration of acetyl-CoA in the cytosol. CoA activation of the purified enzyme is accompanied by an increase in the Vmax, without changing the Km for acetyl-CoA. The Km for acetyl-CoA of the purified enzyme is about 10 to 40 microM. The purification procedure results in a decrease in the Km for acetyl-CoA; under these conditions, CoA activation does not cause further lowering of the Km. CoA activation is accompanied by polymerization of the enzyme. However, CoA activation is not causally related to polymerization. There is one CoA binding site/subunit of acetyl-CoA carboxylase. CoA binding at that site is not affected by the presence of citrate, but palmityl-CoA inhibits CoA binding. CoA alone cannot reverse palmityl-CoA inhibition of the carboxylase. Bovine serum albumin and CoA together can activate the palmityl-CoA-inhibited enzyme. This indicates that the involvement of bovine serum albumin-like protein, CoA, and palmityl-CoA may play a physiologically significant role in the control of acetyl-CoA carboxylase.

Acetyl-CoA Carboxylase↗

The uses and limitations of radioisotopes in the investigation of gastrointestinal diseases.

Advances in the physical and biological sciences have in recent years led to a rapidly increasing use of radioactive agents in clinical medicine. The distinctive properties of these agents have made them invaluable for a large variety of unique in vivo and in vitro diagnostic tests. In order to help the clinician employ such tests productively and realistically, we have attempted to review the present status of radiosotopes with regard to gastrointestinal diseases. Emphasis has been placed not only on their value but also on their limitations; the degree of safety for in vivo application has also been briefly considered.

Adult↗