Biomedical subjects
Publications and source records attributed to M Liu.
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X-14547A is a novel antibiotic produced by a new strain of Streptomyces antibioticus (NRRL 8167). The antibiotic is active in vitro against Gram-positive bacteria and is capable of complexing and transporting divalent as well as monovalent metal cations.
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In 11 fetal sheep experiments, the blood pressure in the fetal aorta (FA) and in the umbilical vein (UV) was measured following umbilical vein occlusion (UVO), as was the fetal heart rate (FHR), pH, Pco2, and oxygen saturation (So2) in both fetal vessels, and umbilical blood flow (Qumb) of the common UV. The fetal electroencephalogram was recorded continuously throughout the experiment. The results (No. = 17) were grouped according to the response of FA So2 into moderate (So2greater than40 per cent, mean 49.8, S.D. 6.3, and severe So2less than40 per cent, mean 20.4, S.D. 9.2). After 8 to 10 seconds, the fetal blood pressure in FA increased. Umbilical vein blood pressure increased to 25 mm. Hg (S.D. 8) and 35 mm. Hg (S.D. 9) in the moderate and severe groups, respectively. As a result of the decreased perfusion pressure (FA-UV blood pressure) across the fetal side of the placenta, the Qumb fell from 147 ml. per kilogram per minute (S.D. 57) and 30 ml. per kilogram per minute (S.D. 55) to 84 ml. per kilogram per minute (S.D. 48) and 120 ml. per kilogram per minute (S.D.22), respectively. The fall in FA So2 was related to the decrease in Qumb: FA So2=37.6 x log Qumb - 22.8 (2alphaless than 0.001). There was a mild decrease in So2 from 70 to 55 per cent when Qumb fell from 250 to 120 ml. per kilogram per minute. Below 80 to 120ml. per kilogram per minute, the fall in FA So2 was almost linear. The So2 in the UV remained constant so that arteriovenous difference for oxygen (AV Do2) increased. Oxygen consumption decreased almost linearly when Qumb fell below 80 to 120 ml. per kilogram per minute. The fetal electroencephalogram showed no significant change in voltage and the faster activities. From these observations, it is concluded that a decrease in Qumb following UVO jeopardizes the fetus only if a critical Qumb of 80 to 120 ml. per kilogram per minute and fetal artery So2 of 50 to 60 per cent is achieved.
Cerebral function and metabolism, morphology and histology of the nervous system, and lung maturity in terms of surfactant production were studied at term in five sheep fetuses thyroidectomized at gestational ages ranging from 104 to 111 days. Compared to age-matched controls, body weight (thyroidectomized animals, 2.8 +/- 0.11 kilograms; controls, 3.9 +/- 0.2 kilograms; P less than 0.0005) and brain weight (thyroidectomized animals, 43.51 +/- 1.38 grams; controls, 48.49 +/- 1.75 grams; P less than 0.05) were significantly reduced. In the nervous system, morphology, histology, brain function, and metabolism were not significantly different from those of the controls. Lung weight was less, but not significantly, and surfactant production was not deficient as compared to that of age-matched controls. The failure to find any disturbance of maturation in the brain and lungs of fetuses thyroidectomized at 104 to 111 days may be related to the relative maturity of the sheep fetus at this age.
This paper contains a preliminary report of the crystal structure of the acid protease from Rhizopus chinensis at 2.5 A resolution. The molecule is bilobal with a large cleft between the lobes. Pepstatin binds in the cleft near the catalytically active Asp-35. The overall folding of the molecule consists primarily of antiparallel beta-strands, there being only four small helices.
The molecular structures of two fungal acid proteases at 3 A resolution have been compared, and found to have similar secondary and tertiary folding. These enzymes are bilobal and have a pronounced cleft between the two lobes. This cleft has been identified as the active site region from inhibitor binding studies. The results of the comparison are discussed in terms of homology among the acid proteases in general.
A variety of transplantable mouse tumor lines were shown to contain murine type C viruses and virus-associated antigens. The type of virus isolated and antigens detected could not invariably be correlated with the original method of tumor induction, but testing of the majority of tumor lines for infectious virus at various levels of in vivo or in vitro passage yielded isolates that were consistent in tissue culture host range for each tumor. In contrast, during the course of in vivo transplantation, some of the lines underwent considerable change in the pattern of virus-associated cell-surface antigens. When the transplanted tumor lines were placed into culture, all showed some alteration in the detectable surface antigens. Upon retransplantation and passage of the cultured cells in mice, the surface antigens gradually returned to the original in vivo patterns and occasionally acquired additional type C virus-associated antigens not detected in the original tumor line. To test for association of antigens with infectious virus, appropriate tissue culture cell lines were infected with the viruses isolated from the tumors. In these infected indicator cells, some new virus-associated cell-surface and virion evelope antigens were detected, but the complete array of antigens found in the original tumor lines was not acquired. These findings indicated the presence of several different type C viruses in long transplanted cell lines and demonstrated that environmental and host cell factors may have major influences on expression of virus-associated antigens.
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The effect of methadone on fetal brain function in terms of the electroencephalogram (EEG) was studied in eight short-term fetal sheep experiments by single injections of 5 to 20 mg. of methadone into the fetal circulation. Plasma methadeone concentrations (determined by radioimmunoassay) greater than 0.065 mg. per cent were associated with an immediate brief decrease in carotid blood flow, a rapid decrease in frequency and amplitude in the EEG that occasionally became isoelectric but recovered, and immediate and relatively prolonged bradycardia. Similar cardiovascular observations were obtained with plasma methadone concentrations less than 0.065 mg. per cent, but the EEG changes were either minimal or not observed. These results indicate that uptake of methadone by the fetal brain is rapid and that electrical activity and heart rate are affected.
Gibbon natural antibody examined by immunoelectron microscopy reacted with the entire envelope of type C virus and with areas on the cell surface equivalent to or smaller than the diameter of a virion in gibbon and human culture cells infected with or releasing type C viruses. The antibody activity was absorbed completely by two cell cultures infected with gibbon ape leukemia virus and by the virus itself, and partially by normal gibbon spleen cells and dog thymus-derived cells infected with baboon endogenous type C virus, and fresh white blood cells obtained from a patient with chronic myelogenous leukemia in acute blastic crisis.
Sera from healthy humans contained naturally occurring antibody against group- or subgroup-specific antigen on the envelope of the following type C viruses isolated from primates: gibbon ape leukemia virus, simian (woolly monkey) sarcoma virus, baboon endogenous type C virus, and putative human type C viruses [HL23V isolated from blood cells of a patient with acute myelogenous leukemia (HL23) and HEL-12V from human embryonic diploid cells (CIH-32)]. Two sera also reacted with C57BL/6 mouse leukemia induced by Friend virus. These results were obtained by indirect immunoelectron microscopy with various virus-producing cells and by absorption tests using as targets gibbon lymphosarcoma cells that release gibbon ape leukemia virus. In a previous report, the presence of natural antibody in sera from healthy gibbon apes was demonstrated. When the specificities of the human and gibbon natural antibodies were compared, the human natural antibody reacted with two nonproducing culture cell lines of human lymphocytic leukemia (CEM-A and MOLT) and with human embryonic diploid (CIH-1(V-) cells [which became type C virus-producing CIH-32(V+) cells after many passages], but did not react with normal gibbon spleen monolayer cells. In contrast, gibbon natural antibody showed no reaction with CEM-A, MOLT, and CIH-1(V-) cells but reacted with gibbon spleen monolayer cells. Neither human nor gibbon natural antibody that was reactive with gibbon ape leukemia virus crossreacted with feline leukemia virus and mouse wild-type AKR leukemia virus. The gibbon lymphosarcoma cells releasing gibbon ape leukemia virus were used in a screening study of sera from healthy humans. Out of 72 sera screened by indirect immunoelectron microscopy using this system, 55 were positive (76%), i.e., 26 out of 35 males (74%) and 29 out of 37 females (78%). The highest incidence of antibody production was in 1- to 10-year-olds and 31- to 40-year-olds, with the adults exhibiting higher levels. Differences in incidence of natural antibody were not found to be sex-linked. These findings suggest that type C RNA viruses related to the gibbon ape leukemia virus and simian (woolly monkey) sarcoma virus family as well as the baboon endogenous type C virus family may be widespread in humans.
The effect of maternal alcohol infusions on fetal cerebral function in terms of the electroencephalogram (EEG) and fetal brain metabolism was studied in 10 fetal sheep experiments. A 9.75 per cent alcohol-dextrose solution was infused at the rate of 15 c.c. per kilogram of maternal weight for 1 or 2 hours. Fetal cerebral uptake of oxygen was unaffected. Blood flow was significantly increased as a result of a greater decrease in resistance than decrease in blood pressure. The cerebral uptake of glucose and the glucose-oxygen utilization ratio were significantly increased. The EEG showed a decrease in amplitude and slowing of the dominant rhythm as the blood alcohol concentration increased and became isoelectric on occasion during the postinfusion period associated with a severe fetal acidosis.
The placental transport of alcohol and its effect on maternal and fetal acid-base balance studied in 10 sheep experiments by the maternal infusion of a 9.75 per cent solution of alcohol-dextrose at a rate of 15 c.c. per kilogram for 1 or 2 hours. Serial maternal and fetal blood sampling during and following the alcohol infusion revealed rapid placental diffusion of alcohol, a highly significant correlation between maternal and fetal blood alcohol concentrations, and a similar peak concentration of approximately 0.230 Gm. per 100 ml. in maternal and fetal blood that differed only in time of onset during the 1 and 2 hour infusion periods. Blood alcohol concentrations remained high for several hours during the postinfusion period. A significant maternal hyperlactacidemia and hyperglycemia were noted but did not result in significant alterations in maternal acid-base balance. An initial fetal metabolic acidosis and later mixed acidosis were observed during the alcohol infusion and worsened during the postinfusion period.
The tissue-culture cell line HT-29, derived from a primary colon adenocarcinoma and previously shown to secrete carcinoembryonic antigen (CEA), was examined by immunoelectron microscopy for the location of CEA in relation to the cells. CEA was closely adjacent to the plasma membrane, a location indistinguishable from that of alloantigens and other tumor-associated antigens.
When Abelson murine leukemia virus (MuLV-A) was inoculated into pristane-primed BALB/c mice, either plasmacytomas (PCT), lymphosarcomas, or their mixed form was induced with a shorter latent period than that for PCT induction in mice treated with pristane alone. All 3 neoplasms were designated Abelson's tumors. The morphology of the induced malignant cells and the presence of known surface antigens were analyzed by electron microscopy. The cell surface antigens (CSA) examined were PC1, X.1, Gross (GCSA), and Moloney (MCSA); viral envelope antigens (VEA) were xVEA, x1-VEA, sub-gsVEA, and MVEA. MuLV-A-pristane-induced PCT cells produced markedly fewer intracisternal type-A particles than did mineral oil-induced PCT cells. Most, if not all, mineral oil-induced PCT cells carried PC1 antigen and produced many extracellular type-C viruses carrying xVEA and x1-VEA, whereas Abelson's tumor cells had both a lower incidence and a smaller amount of PC1 and X.1 antigens and xVEA+ virus and lacked x1-VEA+ virus. In addition, most Abelson's tumors and their type-C viruses did not carry MCSA and MVEA ro GCSA and sub-gsVEA. All the macrophages in the PC1+ Abelson's tumors and many macrophages in PC1-Abelson's tumors contained various amounts of PC1 on their cell surfaces. For these reasons, Abelson's tumors were clearly distinct from pristane- or mineral oil-induced BALB/c PCT and from M-MuLV- ro G-MuLV-induced tumors.
When viral envelope antigens (VEAs) and virus-associated cell surface antigens (CSAs) are used as markers of type C viruses, more heterogeneity of virus populations can be demonstrated than by using host range alone. In the present study, four CSAs (PC1, X.1, GCSA, and MEV-SA1) and three VEAs (xVEA, x1-VEA, and sub-gsVEA) were used as markers of virus populations present in various sublines of the BALB/c embryonic fibroblast BALB/3T3 clone A31 line. Of four spontaneously transformed sublines, two released N-tropic endogenous type C viruses spontaneously after long-term culture and each had distinct antigenic patterns. Treatment with 5-bromodoxyuridine (BrdU) resulted in the detection of X-tropic viruses in all four sublines. The expression of these X-tropic viruses was associated with two different antigenic patterns. When the clonal rabbit corneal SIRC cell line was infected with the X-tropic viruses obtained after BrdU treatment, the cells acquired detectable amounts of only one of the antigenic markers.