D-propranolol and DL-propranolol both decrease conversion of L-thyroxine to L-triiodothyronine.

The effects of propranolol (DL-propranolol) and D-propranolol on thyroid hormone metabolism were studied in six euthyroid volunteers receiving L-thyroxine (T4) and six hypothyroid patients receiving T4 replacement. D-propranolol as well as propranolol decreased L-triiodothyronine (T3) concentrations and the ratio of T3 to T4 in the euthyroid subjects, and D-propranolol decreased these variables in the subjects with hypothyroidism (propranolol was not given to this group). It is concluded from this study and from parallel invitro investigations that the effect of propranolol on the conversion of T4 to T3 is unrelated to its beta-adrenergic blocking activity, and that at low therapeutic doses propranolol may exert appreciable "membrane-stabilising" effects in vivo.     

Miniature two-dimensional thin-layer chromatographic separation of lecithin and sphingomyelin

A miniature two-dimensional thin-layer chromatographic procedure employing silica gel impregnated glass-microfiber chromatography sheets (commercial product, ITLC-type SG sheets) has been developed for the separation of lecithin (L) and sphingomyelin (S) from a standard lipid mixture containing L, S, lysolecithin, phosphatidyl inositol (PI), phosphatidyl serine (PS), phosphatidyl ethanolamine, phosphatidyl glycerol, and diphosphatidyl glycerol. The newly developed procedure eliminates possible interference from PI and PS. Complete separation of L and S was easily achieved with chromatographic solvent migration times of approximately 3 and 2 min for the first and second dimensions, respectively. The lipids were visualized by charring and fluorescent staining techniques. The procedure has been adapted for the separation of L and S from amniotic fluid samples.     

Chemical modifications of actin: effects on interaction with deoxyribonuclease I

Maleylation of lysine residues, nitration of tyrosine residues or modification with 2,3-butanedione or 1,2-cyclohexanedione of arginine residues on actin resulted in a loss of polymerizability of the modified actin. However, only lysine modification produced a complete loss of the deoxyribunuclease I inhibitory ability of actin at low degrees of modification. By the level of one modified lysine per actin monomer, the samples completely lost polymerizability and lost 65% of their inhibitory power against deoxyribonuclease I-catalysed hydrolysis of DNA. By two lysines modified per actin, all inhibitory activity was lost. One lysine residue on actin apparently overlaps both an actin action contact site and an actin-deoxyribnuclease 1 contact site, offering a suggestion as to how deoxyribonuclease I blocks actin polymerization.     

Urinary excretion of a novel hexasaccharide and glycopeptide analogue in fucosidosis.

Repeated Biogel P6 chromatography of the urine from a patient with fucosidosis yielded several fractions containing fucosyloligosaccharides and glycopeptides. Two of these were shown by ¹H nuclear magnetic resonance (¹H-n.m.r.) spectroscopy and permethylation analysis to have the following structures respectively: (I) αfuc (1→3) [βgal (1→4)] βglcNAc (1→2) αman ($\text{1→}\text{3}\text{6}$) βman (1→4) glcNAc and (II) αfuc (1→3) [βgal (1→4)] βglcNAc (1→2) αman ($\text{1→}\text{3}\text{6}$) βman (1→4) βglcNAc (1→4) [αfuc ($\text{1→}\text{3}\text{6}$)] βglcNAc-Asn.     

A spectrofluorimetric investigation of calf thymus DNA modified by BP diolepoxide and 1-pyrenyloxirane

7β,8α-Dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BP diolepoxide, $\text{1}$) and 1-pyrenyloxirane ($\text{2}$) bind chemically to calf thymus DNA. The fluorescence efficiency of pyrenyl groups in mutagen modified DNA varies appreciably with its conformation and decreases in the order: pyrenees, modified denatured DNA and modified native DNA. A particularly interesting observation is that the fluorescence efficiency of mutagen modified DNA intensifies substantially upon denaturation. Our results suggest that the pyrenyl groups in mutagen modified DNA are intercalated between the base pairs of DNA. Since both $\text{1}$ and $\text{2}$ are powerful frame-shifting mutagens for S. typhimurium TA-98, the intercalative covalent binding of these compounds to DNA may provide a molecular basis for their mutagenic activity.     

Halogenated monoterpenes of the red alga Microcladia

The red marine algae Microcladia borealis, M. californica and M. coulteri produce several unusual halogenated monoterpenes including violacene, plocamene-B, plocamene-C, and plocamane-D. The isolation of these terpenes along with a study of their variation in each Microcladia at different locations are described.     

Death of Staphylococcus aureus in Liquid Whole Egg Near pH 8

Incubating and shaking Staphylococcus aureus in liquid whole egg causes a decline in viability. During the period of agitation, the natural pH of the egg rises from about 7.2 to between 8.0 and 8.2 as a result of a loss of carbon dioxide. However, if the pH of the egg is prevented from rising, either by not shaking or by addition of a buffer, S. aureus will grow. The cause of death is traced to the presence of lysozyme of egg white. Interestingly, the action of lysozyme is not attributable to its bacterial lytic property but, instead, to the basicity of the lysozyme molecule. This conclusion is supported by the fact that the lytic property of lysozyme is known to have its optimal activity near neutrality and by the finding that protamine sulfate, a nonenzymatic basic polypeptide, also caused death of S. aureus at pH 8.0 but not at 7.0. It was postulated that the rise in pH renders the bacterial cells more negatively charged, so that in the presence of positively charged molecules like lysozyme or protamine sulfate a complex is formed, agglutinating the cells.     

Purification and regulatory properties of pyruvate kinase from Veillonella parvula.

The nonglycolytic, anaerobic organism Veillonella parvula M4 has been shown to contain an active pyruvate kinase. The enzyme was purified 126-fold and was shown by disc-gel electrophoresis to contain only two faint contaminating bands. The purified enzyme had a pH optimum of 7.0 in the forward direction and exhibited sigmoidal kinetics at varying concentrations o-f phosphoenol pyruvate (PEP), adenosine 5'-monophosphate (AMP), and Mg-2+ ions with S0.5 values of 1.5, 2.0, and 2.4 mM, respectively. Substrate inhibition was observed above 4 m PEP. Hill plots gave slope values (n) of 4.4 (PEP), 2.8 (adenosine 5'-diphosphate), and 2.0 (Mg-2+), indicating a high degree of cooperativity. The enzyme was inhibited non-competitively by adenosine 5'-triphosphate (Ki = 3.4 mM), and this inhibition was only slightly affected by increasing concentration of Mg-2+ ions to 30 mM. Competitive inhibition was observed with 3-phosphoglycerate, malate, and 2,3-diphosphoglycerate but only at higher inhibitor concentrations. The enzyme was activated by glucose-6-phosphate (P), fructose-6-P, fructose-1,6-diphosphate (P2), dihydroxyacetone-P, and AMP; the Hill coefficients were 2.2, 1.8, 1.5, 2.1, and 2.0, respectively. The presence of each these metabolites caused substrate velocity curves to change from sigmoidal to hyperbolic curves, and each was accompanied by an increase in the maximum activity, e.g., AMP greater than fructose-1,6-P2 greater than dihydroxyacetone-P greater than glucose-6-P greater than fructose-6-P. The activation constants for fructose-1,6-P2, AMP, and glucose-6-P were 0.3, 1.1, and 5.3 mM, respectively. The effect of 5 mM fructose-1,6-P2 was significantly different from the other compounds in that this metabolite was inhibitory between 1.2 and 3 mM PEP. Above this concentration, fructose-1,6-P2 activated the enzyme and abolished substrate inhibition by PEP. The enzyme was not affected by glucose, glyceraldehyde-3-P, 2-phosphoglycerate, lactate, malate, fumerate, succinate, and cyclic AMP. The results suggest that the pyruvate kinase from V. parvula M4 plays a central role in the control of gluconeogenesis in this organism by regulating the concentration of PEP.     

The HIV epidemic in China： history, response, and challenge

The first case of AIDS was reported in 1985 in China, but by the early 21st century, the government estimated that there were 840,000 citizens living with HIV/AIDS. The number is increasing rapidly. The major risk groups are injection drug users （IDUSs; 43%） and former plasma donors （27%）, but rates among heterosexual groups are rising rapidly. Sentinel surveillance was initiated in 1986, and now includes IDUs, men-who-have-sex-with-men, sexually transmitted disease clinic attendees, antenatal women, long-distance truck drivers, and sex workers. Although the government was slow to respond to the epidemic in the late 20th century, it has made a vigorous response in the early 21st century. Components of that response include implementation and evaluation of harm reduction programs for IDUs, education to increase knowledge and reduce stigma, treatment and social support for rural and poor HIV/AIDS patients, widespread testing, and increased funding for HIV/AIDS programs. International agencies have been generous in their support of the government initiatives. To successfully combat the epidemic, China needs to develop and train the necessary infrastructure to implement its intervention programs, particularly in the rural areas, to vigorously combat stigma and discrimination, support research especially in the universities and research institutions other than the China Centers for Disease Control, develop a system for efficient exchange of research and program information, and update legislation to reflect the current situation.     

NMR study of in vivo RIF-1 tumors: Analysis of perchloric acid extracts and identification of 1H, 31P and 13C resonances

Perchloric acid extracts of radiation-induced fibrosarcoma (RIF-1) tumors grown in mice have been analyzed by multinuclear NMR spectroscopy and by various chromatographic methods. This analysis has permitted the unambiguous assignment of the ³¹P resonances observed in vivo to specific phosphorus-containing metabolites. The region of the in vivo spectra generally assigned to sugar phosphates has been found in RIF-1 tumors to contain primarily phosphorylethanolamine and phosphorylcholine rather than glycolytic intermediates. Phosphocreatine was observed in extracts of these tumor cells grown in culture as well as in the in vivo spectra, indicating that at least some of the phosphocreatine observed in vivo arises from the tumor itself and not from normal tissues. In the ³¹P-NMR spectra of the perchloric acid extract, resonances originating from purine and pyrimidine nucleoside di- and triphosphate were resolved. HPLC analyses of the nucleotide pool indicate that adenine derivatives were the most abundant components, but other nucleotides were present in significant amounts. The ¹H and ¹³C resonance assignments of the majority of metabolites present in RIF-1 extracts have also been made. Of particular importance is the ability to observe lactate, the levels of which may provide a noninvasive measure of glycolysis in these cells in both the in vivo and in vitro states. In addition, the aminosulfonic acid, taurine, was found in high levels in the tumor extracts.