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Biomedical subjects

T T Sun

Publications and source records attributed to T T Sun.

At least 181 records · Page 10Linked to original sources
PubMed1979

1-aminocyclobutane[11C]carboxylic acid, a potential tumor-seeking agent.

1-Aminocyclobutane[14C]carboxylic acid [C-14) ACBC] was incorporated preferentially by several tumor types in rats and hamsters. The agent was cleared rapidly from rat blood, attaining its maximum tissue concentrations within 30 min after i.v. injection. Carrier ACBC had little effect on the tissue distribution of (C-14) ACBC. This agent showed no affinity for a Staphylococcus aureus abscess in rats. The total excretion was low, 3.6% in 2 hr. (C-11) ACBC was synthesized in amounts up to 415 mCi (55% chemical yield) using our modified Bücherer-Strecker technique. Forty minutes were required for the two-step synthesis and chromatographic purification. ACBC was found to be nontoxic in three animal species. The radiation dose from (C-11) ACBC should be minimal. (C-11) ACBC thus appears to have good potential as a tumor-seeking agent, particularly when used with a positron emission computed tomograph.

Adenocarcinoma↗
PubMed1979

DL-[Carboxyl-11C]tryptophan, a potential agent for pancreatic imaging; production and preclinical investigations.

In animal studies, DL-[carboxyl-14C]tryptophan [DL-Try(C-14)] showed a high specificity for the pancreas, which suggested the potential of DL-[carboxyl-11C]tryptophan [DL-Try(C-11)] for clinical pancreatic inaging. The blood clearance and tissue uptake of the amino acid were very rapid, and no carrier effect was observed through a dose of 5 mg/kg. None of three transplanted hamster pancreatic adenocarcinomas that we studied showed a selective uptake of DL-Try(C-14) by the tumor, and none of the three enzymatic regimens investigated gave significant enhancement of the pancreatic specificity. Commercial L-Try(C-14) gave slightly better pancreatic specificity than the analogous racemic compound but without enough improvement to warrant attempts at optical resolution. DL-Try(C-11) was synthesized in amounts up to 325 mCi using a rapid, high-temperature, high-pressure modification of the Bücherer-Strecker amino acid synthesis. Yields ranged from 30--60%, and a total of 40 min was required for synthesis and chromatographic purification. DL-Try(C-11) thus appears to have significant potential as a clinical pancreas-imaging agent, particularly when used in conjunction with positron computerized transaxial tomography.

Adenocarcinoma↗
PubMed1978

Keratin filaments of cultured human epidermal cells. Formation of intermolecular disulfide bonds during terminal differentiation.

Human epidermal cells grown in culture synthesize abundant keratins. These keratins are similar to those of stratum corneum of human epidermal callus in their insolubility in dilute aqueous buffers, their molecular weight range of 40,000 to 60,000, their immunolgical reactivity, and their ability to assemble into 80 A tonofilaments in vitro; but there are differences in the molecular weights of some of the proteins, the number of components, and their charge heterogeneity, related at least in part to phosphorylation. About 30% of all the proteins of living cultured keratinocytes consists of keratins, compared with over 85% of stratum corneum. All the keratins of human stratum corneum were found to be cross-linked by intermolecular disulfide bonds while most keratins of the living cells were not. As the cells mature in Methocel-stabilized suspension culture, their keratins become increasingly disulfide cross-linked. When uncross-linked tonofilaments of living keratinocytes are dissolved in 8 M urea and the filaments reconstituted in vitro their keratins become disulfide cross-linked under aerobic conditions and consequently insoluble in solutions of 8 M urea or sodium dodecyl sulfate. The results indicate that the uncross-linked state of the keratins in living cells is due to the reducing intracellular environment and not to a precursor state related to the primary structure of the proteins. The disulfide cross-links stabilizing the keratin filaments must be distinguished from the epsilon-(gamma-glutamyl)lysine cross-links stabilizing the cornified cell envelope.

Cell Differentiation↗
PubMed1978

Immunofluorescent staining of keratin fibers in cultured cells.

Antibody prepared against a group of keratins purified from human stratum corneum was used to identify cells containing keratins by immunofluorescence. In sectioned tissue and in culture, keratinocytes of skin and other stratified squamous epithelia-whether human, rabbit of mouse-stained strongly, indicating homologous amino acid sequences in the keratins of these species. In all cases, the antibody revealed a dense cytoplasmic network of discrete fibers probably consisting of aggregated (tono-) filaments. The pattern of staining was not affected by cytochalasin B or colcemid. No keratins were detected in cultured cells of mesenchymal origin (3T3, NIL, BHK, human diploid fibroblasts) or in connective tissues, indicating that the 100 A filaments of fibroblasts are not related to the keratins. Keratinocytes at all stages of differentiation, including basal cells, stained brightly and therefore contained abundant keratins.

Animals↗
PubMed1978

Effect of structure on tumor specificity of alicyclic alpha-amino acids.

The selective affinity of [carboxyl-11C]-1-aminocyclopentanecarboxylic acid (ACPC) for tumor tissue has led us to study the tumor-localizing characteristics of a series of alicyclic alpha-amino acid analogs of ACPC. The tissue distributions of [14C]-1-aminocyclopropanecarboxylic acid, 1-aminocyclobutanecarboxylic acid (ACBC), 1-aminocyclohexanecarboxylic acid, 1-amino-2-methylcyclopentanecarboxylic acid were compared with that of ACPC in Buffalo rats bearing Morris 5123C hepatomas. ACPC and ACBC were found to have significantly higher tumor-to-nontumor concentration ratios than the other four amino acids. ACBC generally had higher tumor-to-nontumor ratios than did ACPC, significantly so for muscle, kidney, and testis and marginally so for blood. These results suggest that [carboxyl-11C]ACBC may be a better agent than [carboxyl-11C]ACPC for tumor imaging by positron tomography.

Amino Acids↗
PubMed1978

[1-11C] DL-valine, a potential pancreas-imaging agent.

There is a great need for a better pancreas-imaging agent. Studies with [1-14C] DL-valine have shown this amino acid to have a high pancreatic specificity in the four animal species examined. The tissue distribution was almost optimal by 30 min after injection, and no carrier effect was observed through a dose of 5 mg/kg. [1-11C] DL-Valine was synthesized in amounts up to 363 mCi using a rapid (T1/2 = 20.4 min for C-11), high-temperature, high-pressure modification of the Bücherer-Strecker amino acid synthesis. Purification was by anion-exchange followed by cation-exchange chromatography. [1-11C] DL-Valine was obtained in a 70% chemical yield with a total synthesis and purification time of 45 min. Studies in animals have demonstrated that it is a potentially useful new agent for clinical pancreatic imaging.

Animals↗
PubMed1977

Cultured epithelial cells of cornea, conjunctiva and skin: absence of marked intrinsic divergence of their differentiated states.

Keratinocytes of three different epithelia grown in cell culture express a large number of differentiation markers with either no differences or relatively small differences, depending on the species. Much of the distinctive phenotype of these epithelia in vivo must be due to external modulation and relatively little, at least in the case of the human, to permanent intrinsic divergence during development.

Animals↗
PubMed1977

Control of a cell surface major glycoprotein by epidermal growth factor.

When the serum concentration of the culture medium is below 0.7 per-cent, 3T3 mouse cells lose most of their large external transformation sensitive (LETS) protein at the cell surface, Subsequent addition of epidermal growth factor results in the reappearance of massive fibrillar LETS protein networks on the surface of conluent 3T3 cells. Thirteen other hormones tested do not have this effect. It appears that epidermal growth factor can control the expression of LETS protein.

Blood↗
PubMed1977

Properties of an epithelial cell type in culture: the epidermal keratinocyte and its dependence on products of the fibroblast.

Keratinocytes of stratified squamous epithelium can be grown serially in culture and retain the various markers typical of their form of differentiation. In order to form colonies at each transfer, the keratinocytes must be suitably supported by fibroblasts. Established keratinocyte lines of teratomal origin show this dependence, as do diploid strains of finite culture life derived from human skin. For at least some keratinocyte lines, this requirement can be satisfied by soluble products elaborated by the fibroblasts. It is suggested that epithelial cells in general may not be independent cell types and that their poor cultivability may be due to failure to provide suitable fibroblast support. The existence of a number of established lines of epithelial origin that can grow without such support and of lines of fibroblastic origin which cannot support keratinocytes suggests that both epithelial dependence and the fibroblast supporting function can sometimes be lost in established cell lines.

Cell Adhesion↗
PubMed1976

Differentiation of the epidermal keratinocyte in cell culture: formation of the cornified envelope.

Human epidermal keratinocytes grow from single cells into stratified colonies. Cells in the upper layers of the colonies lose their ability to divide and begin terminal differentiation. In this process, there develops a cornified cell envelope that remains insoluble after heating in solutions of sodium dodecylsulfate and beta-mercaptoethanol. The insolubility of the cornified envelope depends upon proteins, since after treatment with proteolytic enzymes, the envelope becomes soluble in the detergent. Cells with cornified envelopes can be identified under the light microscope either in living colonies or following fixation and silver nitrate staining. Keratinocytes of the basal layer move in a characteristic way, but cornified cells do not move at all and form an immobile upper layer in the colonies. Keratinocytes disaggregated from growing colonies are of differing size and density, and can be separated on isopycnic gradients of Ficoll. The DNA-synthesizing cells are small (mean diameter 14 mum). The nonmultiplying cells are large and have a protein content proportionate to their size. Their final diameter may exceed 30 microns (volume increase greater than 10 fold). Cornified envelopes are found in some of the large cells but in none of the small. In growing colonies, usually 5-10% of the cells have cornified envelopes. The fraction is reduced in colonies growing in the presence of epidermal growth factor. Strain XB, an established keratinocyte line of mouse teratomal origin, also forms cornified envelopes, but the kinetics of the process are different, indicating that the program of terminal differentiation is not initiated at corresponding times in the two cell types.

Cell Adhesion↗
PubMed1976

Carboxyl-labeled 11C-1-aminocyclopentanecarboxylic acid, a potential agent for cancer detection.

Carboxyl-labeled 11C-1-aminocyclopentanecarboxylic acid (11C-ACPC) has been prepared in multimillicurie amounts. The conversion of H11CN to 11C-ACPC (t1/2 = 20.4 min) was accomplished by a rapid (20-min) two-step high-temperature modification of the Bücherer-Strecker amino acid synthesis technique, which should be applicable at other accelerator installations. Purification was by ion exchange techniques. Animal studies have indicated that 11C-ACPC is a potential tumor-localizing agent for detecting cancer in humans by nuclear medicine scanning techniques.

Animals↗
PubMed1975

The protein topography of the E. coli 30S ribosomal subunit: a preliminary model E. coli/30S subunit/ribosome/spatial arrangement of proteins.

A three dimensional model is presented which shows the apatial arrangement of 20 of the 21 proteins of the 30S ribosomal subunit of Escherichia coli. The model fulfills several purposes: (a) It summarizes currently available structural and functional data on ribosomal proteins; (b) It suggests an interesting correlation between stoichiometry and function. Functional proteins are both clustered and fractional; (c) It can be evaluated in relationships or point out critical experiments by which it can be tested.

Bacterial Proteins↗
PubMed1972

Similarity in the size and number of ribosomal proteins from different prokaryotes.

The ribosomal proteins from nine species of prokaryotes have been compared by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The stained gels were scanned spectrophotometrically, the weight and number average molecular weights were calculated, and the detailed distribution of the proteins as a function of molecular weight was determined. By all of these criteria, the ribosomal proteins from all the species closely resembled each other, despite differences in the pattern of protein bands by conventional disc-gel electrophoresis. Therefore, it is suggested that the structural requirements for the assembly of ribosomal subunits have imposed limitations on the evolution of the ribosomal proteins and that their size has been highly conserved.

Azotobacter↗