Blood gas determinations in hypothermic mammals.
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Anesthesia↗
Biomedical subjects
D C Lee
Publications and source records attributed to D C Lee.
Variation in cardiac output with acid-base changes in the anesthetized dog.
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Acidosis↗
Presynaptic and postsynaptic actions of procainamide on neuromuscular transmission.
Procainamide (PA), a cardiac anti-arrhythmic agent, was applied in vitro to the rat neuromuscular junction and its effect on neuromuscular transmission was investigated using intracellular microelectrode recording techniques. Clinically relevant doses of PA produced a dose-dependent decrease in the amplitude of spontaneous miniature end-plate potentials (MEPPs) and a marked increase in the half-decay time without altering MEPP frequency or resting membrane potential. The amplitude of impulse-evoked end-plate potentials was also reduced in a similar dose-dependent manner, with a marked prolongation of the decaying phase. Direct quantal analysis using magnesium-blocked preparations showed that the drug also caused a reduction in the mean number of acetylcholine quanta released per nerve impulse. This presynaptic inhibitory effect of the drug, however, contributed less to the overall blocking action than did the postsynaptic effect. The junctional effects of the drug were completely reversible, with all affected parameters returning to the control levels after washout of PA with control solution. These direct inhibitory actions on neuromuscular transmission could account for the clinical exacerbations associated with the administration of PA to patients with myasthenia gravis and other neuromuscular diseases.
Animals↗
Purification and characterization of thermostable D-hydantoinase from thermophilic Bacillus stearothermophilus SD-1.
A thermostable D-hydantoinase of thermophilic Bacillus stearothermophilus SD-1 was purified to homogeneity using an immuno-affinity chromatography. The affinity chromatography that employed polyclonal antibody immobilized on Sepharose 4B was simple to operate and gave a purification yield of 60% of enzyme activity. Molecular mass of the enzyme was determined to be about 133.9 kDa by gel filtration chromatography and the molecular mass of the subunit was 54 kDa on SDS-PAGE. Mass spectrometric analyses were also performed for the determination of the molecular mass of the native enzyme and its subunit. The apparent molecular masses were 51.1 and 102.1 kDa for the subunit and native enzyme, respectively. Based on the molecular masses determined by these two methods, it is suggested that the D-hydantoinase exists as a dimeric conformation in the cell. Isoelectric pH of the enzyme was observed to be 4.47. It was found that the enzyme requires one manganese ion per molecule of enzyme for the activity. The optimal pH and temperature for the catalytic activity were about 8.0 and 65 degrees C, respectively. The half-life of the enzyme was estimated to be 30 min at 80 degrees C, confirming that the enzyme purified is one of the most thermostable D-hydantoinase reported so far. Kinetic constants of the enzyme for different substrates were also determined.
Amidohydrolases↗
Sequential polypeptides. 2. Helix--coil transition in poly(gamma-benzyl epsilon-carbobenzoxy-L-lysyl-L-glutamate).
Helix--coil transitions of an alternating copolypeptide poly(gamma-benzyl epsilon-carbobenzoxy-L-lysyl-L-glutamate) (poly[Lys(Z)-Glu(OBzl)]) in binary mixtures of dichloroacetic acid (DCA) and ethylene dichloride (EDC) were investigated by optical rotatory dispersion (ORD). The ORD data obtained were analyzed to evaluate the equilibrium constant s for helix formation and the cooperativity parameter sigma. The values of sigma1/2 are substantially independent of temperature and solvent composition, yielding 0.4 X 10(-2) on the average. The transition enthalpy deltaHc at the transition point decreases from 291 to 154 cal mol-1 as the DCA content is increased from 56 to 64 vol%. At about 20 degrees C and at 58 vol% DCA, poly[Lys(Z)-Glu(OBzl)] in binary mixtures of DCA and EDC undergoes a solvent-induced transition. This DCA content is intermediate between those for poly(gamma-benzyl L-glutamate) and poly(epsilon-carbobenzoxy-L-lysine) in the same binary solvent and close to that of an equimolar random copolymer of the two peptides. However, the s of poly[Lys(Z)-Glu(OBzl)] is not a geometrical mean of those of the parent homopolypeptides. This fact suggests that the helical conformation of the copolypeptide is stabilized by a conformational induction operative between adjacent residues.
Benzyl Compounds↗
Cloning and sequence analysis of a cDNA for rat transforming growth factor-alpha.
Transforming growth factors (TGFs) are mitogenic polypeptides produced most conspicuously by transformed cells and conferring on normal cells several phenotypic alterations associated with transformation. TGFs comprise two distinct sets of molecules: TGF-alpha s are structurally similar to epidermal growth factor (EGF), binding to and inducing the tyrosine phosphorylation of the EGF receptor in a manner indistinguishable from that of EGF. In addition, the 50-amino acid rat TGF-alpha has 33 and 44% homologies with mouse and human EGFs, respectively, and shares with EGFs a conserved pattern of three disulphide bridges. Thus, it has been proposed that TGF-alpha s belong to a family of EGF-like polypeptides. TGF-beta s, on the other hand, display no measurable binding to EGF receptors, but potentiate the growth-stimulating activities of TGF-alpha. Here we report the isolation of a complementary DNA clone encoding rat TGF-alpha. This cDNA hybridizes to a 4.5-kilobase (kb) messenger RNA that is 30 times larger than necessary to code for a 50-amino acid polypeptide and is present not only in retrovirus-transformed rat cells but also at lower levels in normal rat tissues. The nucleotide sequence of the cDNA predicts that TGF-alpha is synthesized as a larger product and that the larger form may exist as a transmembrane protein. However, unlike many polypeptide hormones (including EGF), cleavage of the 50-amino acid TGF-alpha from the larger form does not occur at paired basic residues, but rather between alanine and valine residues, suggesting the role of a novel protease.
Animals↗
Integral membrane glycoprotein properties of the prohormone pro-transforming growth factor-alpha.
Transforming growth factor-alpha (TGF-alpha) is a mitogenically active polypeptide hormone produced by acutely proliferating neoplastic and embryonic tissues. Molecular cloning of TGF-alpha cDNA from human and rat has indicated that this factor is synthesized as part of a larger precursor, proTGF-alpha. An intriguing feature of proTGF-alpha is that it contains a sequence of 24 hydrophobic amino acids following the bioactive TGF-alpha sequence. Similar hydrophobic sequences present in transmembrane proteins are cotranslationally anchored into the phospholipid bilayer of the rough endoplasmic reticulum, suggesting the possibility that pro TGF-alpha might be an integral membrane protein. Other secretory proteins including all known prohormones lack membrane anchoring sequences and are completely translocated across the endoplasmic reticulum membrane. To address the question of whether proTGF-alpha is as an integral membrane protein we have translated rat proTGF-alpha mRNA transcripts in the presence of rough endoplasmic reticulum membrane vesicles. The results indicate that proTGF-alpha is synthesized as an integral membrane glycoprotein. The 50-amino-acid TGF-alpha sequence in proTGF-alpha is exposed to the fluid extracellular phase where it can be released after cleavage by the appropriate enzyme.
Amino Acid Sequence↗
Modification of cardiovascular function in dogs by acupuncture: a review.
Acupuncture at Jen Chung (Go-26) in dogs under halothane anesthesia produces sympathomimetic-like effects on the cardiovascular system. This response can be inhibited by pretreatment with propranolol and to a lesser extent with phentolamine. Severe hypotension and cardiac arrest produced by hypoxia in dogs under halothane anesthesia can be reversed by acupuncture at Jen Ying (St-9). This also was interpreted as a sympathomimetic-like effect. Acupuncture at Tsu San Li (St-36) results in a parasympathomimetic-like effect on the cardiovascular system which can be inhibited by atropine. A parasympatholytic-like effect resembling that produced by atropine can be obtained in dogs with sinus arrhythmia and pulsus alternans by acupuncture at Yang Hsi (LI-5).
Acupuncture Therapy↗
TGF alpha is dispensable for skin tumorigenesis in Tg.AC mice.
Alterations in growth factor signaling pathways frequently accompany the development and maintenance of epithelial neoplasia. Transforming growth factor alpha (TGF alpha) and its epidermal growth factor receptor have been thought to play an especially important role in epithelial neoplasia. In this study, mice were derived genetically deficient (null) in functional TGF alpha expression and carrying the Tg.AC/v-Ha-ras transgene. The goals were to determine if (a) papillomagenesis was dependent on TGF alpha and (b) progression to malignancy was dependent on TGF alpha expression. Groups of male and female mice heterozygous or homozygous for the TGF alpha null allele and hemizygous for the Tg.AC transgene were treated twice weekly for 10 or 15 wk with doses of 12-O-tetradecanoylphorbol-13-acetate (TPA) known to produce papillomas in Tg.AC mice. Papillomas were readily induced in both male and female TGF alpha null mice. Malignant progression of papillomas was observed in all TGF alpha null treatment groups. Additionally, we examined the response of TGF alpha null mice to full thickness dorsal wounds, a stimulus known to promote papillomagenesis in Tg.AC mice. As in the TPA study, papillomas were induced in both male and female TGF alpha null mice. These studies indicate that TGF alpha is not required for the induction and maintenance of papillomas nor is it essential for the malignant conversion of papillomas in Tg.AC mice.
Animals↗
Esophageal cytology in patients receiving cytotoxic drug therapy.
Our experience with the cytology of esophageal brush specimens from patients who did not have either gastric or esophageal cancer but who received a variety of chemotherapeutic agents is reported. Ten patients received chemotherapy alone, and nine received combined chemotherapy and radiation therapy. Of the ten patients, three showed evidence of moderate to severe epithelial atypia, which was not seen in the combined treatment group or the control group. The cytologic atypias in the three patients consisted of variation in nuclear size with crowding and overlapping, an increased nuclear-cytoplasmic ratio and multiple nucleoli, many of which varied in size and shape. There was also evidence of cell death and keratinization. Although these patients had not been irradiated, other striking changes were similar to those seen following radiation therapy. The cytologic changes reported here pose a serious diagnostic problem because they may be so severe as to mimic malignant transformation. Evidence of infection by herpes simplex alone or herpes simplex associated with Candida was seen in 32% of the treated patients and in 4% of the control group.
Antineoplastic Agents↗
Intranuclear cytoplasmic inclusions in carcinoma of the thyroid gland.
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Carcinoma↗