Biomedical subjects
Publications and source records attributed to Y F Wang.
A mutation at nucleotide 1101 of Sindbis virus ts11 nsP1 caused temperature-sensitive negative-strand synthesis and suppressed the 24R phenotype, which is caused by a mutation in nsP4. Nonstructural proteins synthesized and accumulated by ts11 at 40 degrees C did not cause the reactivation of negative-strand synthesis upon return to 30 degrees C and did not prevent the formation of new replication complexes at 30 degrees C.
Recombinant growth factors have been shown to alter the sensitivity of acute myeloblastic leukemia (AML) blast cells to cytosine arabinoside (ara-C) in culture. The mechanism is controversial and suggestions for it include changes in ara-C metabolism, changes in cell cycle parameters, and changes in the balance between self-renewal and determination in blast stem cells. We addressed this issue by measuring the cisplatin sensitivity of freshly obtained AML blasts in rG-CSF, rGM-CSF, or the two together. For comparison, simultaneous measurements of ara-C sensitivity were made. We found that exposure to different factors in suspension altered the cisplatin sensitivity of AML blasts in the same direction as the change observed in ara-C sensitivity. Similar changes in cisplatin sensitivity were seen when cells were briefly exposed to the drug, washed, and then grown in suspension in the presence of different growth factors. Control experiments showed that the conditions in suspension, not in the clonogenic assay in methylcellulose, were responsible for the changes in cisplatin sensitivity. The capacity of high specific activity to inactivate clonogenicity was tested at several times under growth conditions which altered the sensitivity of cells to cisplatin. Whereas changes in survival after 3HTdR and cisplatin both were seen with time, growth conditions that altered cisplatin sensitivity were not associated with changes in 3HTdR toxicity. The data do not support explanations of the effects of growth conditions on drug toxicity which depend either on drug metabolism or cell cycle effects. Instead, the findings are consistent with a model that postulates an association between drug sensitivity and the balance between self-renewal and differentiation in the blast population.
Cytosine arabinoside (ara-C) and cis-dichlorodiammineplatinum II (cisplatin) are lethal to mammalian cells by very different mechanisms; however, they share interactions with the biology of blast cells in acute myelogeneous leukemia (AML). Both agents are more toxic to AML blasts in suspension than when a clonogenic assay in methyl cellulose is used; both agents are more toxic in suspension in the presence of rG-CSF than with rGM-CSF. Accordingly, preclinical tests were undertaken of cisplatin and ara-C in combination. At the same time, a phase I/II clinical trial of the combination was conducted, using AML patients refractory to treatment or in relapse. In the laboratory, blasts from eight AML patients were tested against each agent singly and in combination. The observed survival values for the mixture were compared with those predicted by assuming either an additive effect or a more general effect that allows synergism or antagonism. Blasts from two patients were tested with this design in the presence of rG-CSF or rGM-CSF. In most instances the toxic effects of ara-C and cisplatin were additive. Evidence of synergism was seen in blasts from three patients.
This paper describes the properties of a continuous cell line derived from the blast cells of a patient with acute myeloblastic leukemia (AML), secondary to the treatment of Hodgkin's disease. The line grows slowly without stimulation but responds to interleukin-3 (IL-3), GM-CSF and mast cell growth factor (MGF), a ligand for the receptor encoded by the c-kit oncogene. When OCI/AML-4 cells are exposed to MGF with IL-3 or GM-CSF, additive or synergistic effects are seen. Combinations of MGF and G-CSF, IL-6 or CSF-1 give less growth than MGF alone. OCI/AML-4 cells are sensitive to retinoic acid; a dose related decrease in clonogenic cells is observed when OCI/AML-4 cells are exposed to retinoic acid in suspension culture. OCI/AML-4 cells are sensitive to cytosine arabinoside (ara-C), but the ara-C dose-response curve can be changed by altering the regulatory milieu in suspension culture. The cells are more ara-C sensitive in MGF or G-CSF than in IL-3 or GM-CSF. Following a 24 h exposure to retinoic acid, the ara-C sensitivity increases; in contrast, after a similar exposure to hydrocortisone, the cells become less ara-C sensitive. These changes in ara-C sensitivity occur in cells that are actively making DNA, as indicated by the reduction in colony formation after exposure to tritiated thymidine. Since OCI/AML-4 cells respond to many of the regulators that affect the growth of freshly obtained AML blast cells, it is proposed that this cell line may be useful for the study of regulation on AML in general and the interaction between different regulators in particular.
The administration of Li2CO3 to female LACA mice for three consecutive days before or after 4Gy whole body gamma-irradiation appeared to have both preventive and therapeutic effects on radiation-induced leucopenia, especially on the depression of CFU-GM. It is effective in small dosage, short course, and even when given 24 hours after irradiation.
In this series of studies, the innervation patterns of whole-mount preparations of bicuspid and tricuspid valves were studied by light microscopy in the mouse, rat, guinea pig, and opossum. The acetylcholinesterase-positive networks of nerve fibers showed many similarities in the basic patterns of valve innervation in all of the species studied, but several interspecies variations were observed. The basal zone of the valve adjacent to the fibromuscular atrioventricular ring displayed the most dense plexus of nerves, with acetylcholinesterase-positive fibers being seen across the width of the valve. In the intermediate zone of the valve, less dense plexuses of nerve fibers were found; and these were more numerous in the cuspal areas and less numerous in the intervening commissural areas. In the distal portions of the valve, nerve networks arborized extensively, with some of their nerve fibers extending toward the chordae tendineae and the free edges of the valve cusps. Only in the guinea pig and opossum did these fibers reach the free margin of the valve cusp, where they either ended directly as free nerve endings or lay parallel to the free edge of the cusp, often running between adjacent chordae tendineae. Although the patterns of innervation were similar in both bicuspid and tricuspid valves, the innervation density of the bicuspid valve was greater than that of the tricuspid valve for each species examined. A distinguishing feature of guinea pig and opossum tricuspid valves was that their chordae tendineae were relatively more prominent and more densely innervated than the bicuspid chordae tendineae. Free nerve endings with no light microscopic evidence of specialization were present throughout the bicuspid and tricuspid valves of all species studied. Some nerve endings in the opossum showed evidence of specialization, with brush-like arborizations leading to presumed free terminals seen chiefly in the distal zone of the valve cusps. Although some general tendencies were apparent, we have demonstrated that interspecies heterogeneity exists in the terminal networks of the atrioventricular valves of mouse, rat, guinea pig, and opossum.
D-galactosamine produces an early defect in protein synthesis, independent of its effects on RNA synthesis. Here we show that the defect in protein synthesis is inherent in purified ribosomal subunits in vitro. Further, galactosamine treatment is associated with an 85% decrease in methylation of ribosomal RNA, involving all sites (2'-0-ribose and base positions), intact ribosomes from galactosamine-treated animals can be methylated to a greater extent than control ribosomes and in vitro methylation restores their functional capacity. Statistical analyses of these data, along with those with a number of other hepatotoxins, reveal a correlation coefficient of r = 0.95 (p less than 0.003) between protein synthetic capacity and ribosomal RNA methylation, and linear regression accounts for more than 90% of the observed variation. In contrast, no relationship was found between nucleolar RNA methylation and protein synthetic capacity. A relationship of borderline statistical significance was found between messenger RNA methylation and protein synthetic capacity, but it does not appear consistent with results obtained after CCl4 intoxication. These results lend strong support to the notion that methylation status of ribosomal RNA is an important control for protein synthesis in quiescent hepatocytes and that net hypomethylation is a common response to such divergent hepatotoxins as CCl4, ethionine and D-galactosamine.
To investigate the prevalence of hepatitis D virus (HDV) and hepatitis B virus (HBV) infection among intravenous drug abusers in Taiwan, a total of 761 male prisoners, including 680 intravenous drug abusers, were studied for serological markers of HBV and HDV. Questionnaires were distributed to evaluate the risk factors for HDV infection and also to estimate the strength of association among HDV infection and the risk factors. HBV infection was common, and the positive rates of HBV markers between intravenous drug abusers and non-drug abusers were not statistically different. However, the positive rate of the antibody to HDV was significantly higher among intravenous drug abusers than among non-drug abusers (21.3% vs. 8.6%). Of 131 chronic HBV carriers with intravenous drug abuse, 119 (91%) were anti-HD positive. Using multiple logistic regression models, we found that the most important risk factor for HDV infection was hepatitis B surface antigen (HBsAg) carriage, and intravenous drug addiction the next. A matched case-control study also was conducted to compare liver function tests among both anti-HD- and HBsAg-positive group anti-HD-negative, and HBs-AG-positive group as well as those with neither positive. Statistically significant difference in liver function tests was not found. It is concluded that the HBsAg carriers with intravenous drug abuse in Taiwan are commonly HDV infected with and that the infection does not seem to affect the liver as assessed by liver function tests.
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Previous work suggested that the major Mr 46,000 ATP-binding protein [a putative nucleoside triphosphatase (NTPase)] found in rat liver nuclear scaffold (NS) may be proteolytically derived from lamins A/C. To definitively establish this identification, we undertook a series of photolabeling, proteolysis, and immunoprecipitation experiments. Mice were immunized with human lamin C expressed in bacteria, and monoclonal antibody-producing hybridomas were obtained. The purified monoclonal antibodies all recognized lamins A and C on immunoblots of NS, as well as Mr 46,000 or 34,000 proteolytic fragments as minor components. The Mr 46,000 photolabeled band was the only major NS component photolabeled with low concentrations of azido-ATP, and it was immunoprecipitated with anti-lamin monoclonal antibodies. To preclude the possibility that the photolabeled Mr 46,000 protein represented a minor component which comigrated with the Mr 46,000 lamin fragment and which specifically associated with lamins A/C during immunoprecipitation, a series of proteolytic digestions were undertaken. Digestion of the photolabeled Mr 46,000 peptide with chymotrypsin and staphylococcal protease V8 produced a limited number of photolabeled fragments, all of which comigrated with major stainable fragments produced from the Mr 46,000 lamin fragment. Cyanogen bromide cleavage of the photolabeled Mr 46,000 polypeptide, followed by polyacrylamide gel electrophoresis or high performance liquid chromatography/amino acid analyses, defined the COOH-terminal cleavage site as the Y residue at amino acid 376 and localized the photolabeled site to the COOH-terminal region (amino acids 372-376). In support of this proposed proteolytic cleavage site, specific assays with tyrosine-containing thiobenzyl ester substrate documented the presence of NS protease activity which cleaves at tyrosine residues; this activity shows a Km of 0.2 mM and a Kcat of approximately 250/s. Parallel experiments with mildly proteolyzed cloned lamin C preparations showed selective photolabeling of an Mr 34,000 fragment, which corresponds to a proteolytic breakdown product of the Mr 46,000 NS polypeptide; this Mr 34,000 photolabeled fragment was also immunoprecipitated with anti-lamin monoclonal antibodies and contained the same photolabeled site as the Mr 46,000 peptide. Cloned lamin C preparations were inactive in NTPase assays but did exhibit substantial ATP binding with an apparent KD = 4 x 10(-5) M ATP. These results indicate that the major Mr 46,000 photoaffinity-labeled protein in NS, which represents the putative NTPase thought to participate in nucleocytoplasmic transport, is derived from lamin A or lamin C by NS proteolytic activity which exposes a cryptic ATP-binding site near the highly conserved end of coil-2.(ABSTRACT TRUNCATED AT 400 WORDS)
We report a 2 amnions, 1 chorion, single placenta, monozygotic identical twins, who were born by a mother with a subclinical rubella infection during the gestation; one twin had a congenital rubella infection, the other escaped from it. Both twins were premature and small for their gestational age at birth. They both had an intraventricular hemorrhage ascribed to prematurity. One had a strong positive rubella IgM antibody for more than 3 months and a persistent IgG antibody for more than 1 year. The other had a fading rubella IgG antibody within 3 months, and a negative IgM. The baby with the congenital infection of rubella did not have a defective appearance, but the auditory brain stem evoked potential test showed abnormal findings. In monozygotic identical twins, vessel communication usually exist and the escape of a twin from rubella is a rare condition; there have been only two such events reported in the English literature.
This paper intend to introduce the therapeutic method of combining TCM and WM as well as the laboratory study to 91 patients with malnourished vulvae. The results showed that the concentration of the luteinizing hormone (LH) in the patients' serum was evidently lower than that in the control group (P less than 0.01). The concentration of follicle-stimulating hormone (FSH) was evidently higher than that of the control group (P less than 0.01). The serum LH of the patients in cured group tended to be higher, and approximated to normal level (P greater than 0.05); the concentration of FSH got lower, and reached to normal level (P less than 0.05). The estradiol (E2) levels in the serum during the ovulation period and follicular period were obviously lower than that in the control group (P less than 0.01; P less than 0.05). The progesterone (P) level during the ovulation period was lower than that in the control group (P less than 0.05). The kraurosis index of the cast-off cells from the labium minus of the vagina in the test group was lower than that in the control group, but it was obviously higher in the cured group, and approximated to normal control group.
Of the 23 amino acids tested for their effect on the membrane potential of incubated toad oocyte, alanine, leucine and lysine were found to cause a decrease of polarization (depolarization) and K+ permeability, while tryptophan causes an increase of potential (hyperpolarization) and K+ permeability. For the rest 19 amino acids, no membrane effects were observed. Accompanying the alanine, leucine and lysine caused depolarization, the oocyte progesterone content became doubled and the maturation process hastened. These effects could be completely blocked by 1 mmol/L dibutyryl cAMP (db-cAMP) or 50 mumol/L estradiol. Tryptophan on the other hand could block the progesterone (10 mumol/L) induced depolarization but had no effect on the db-cAMP induced hyperpolarization. The regulatory function of the amino acids and steroid hormones underlying oocyte maturation is discussed.
Six compounds were isolated from the root of Astragalus chrysopterus Bunge. One of them was identified as a new triterpenoid glycoside, named astrachrysoside A. Its structure was elucidated as 3-O-[alpha-L-rhamnopyranosyl (1----2) beta-D-xylopyranosyl]-cycloastragenol on the basis of physicochemical evidence and chemical reactions. The others were shown to be known compounds, astrasieversianin XV (II), 7,2'-dihydroxy-3',4'-dimethoxy-isoflavane-7-O-beta-D-glucoside (III), soyasaponin I, daucosterol and beta-sitosterol. Full assignment of the chemical shift signals of II and III were established by various 2D-NMR techniques.
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A total of 2432 primary school children, aged 7-14 yrs. in urban areas of Beijing, were evaluated with the Children's Behaviour Questionnaire developed by Rutter. The frequency of behaviour problems in primary school was 8.3%-7.4% antisocial behaviour and 0.62% neurotic behaviour. Behaviour problems were higher in boys than girls: antisocial behaviour was dominant in boys, while neurotic behaviour was common in girls. The frequency of behaviour problems varied significantly with the different social environments in which the children were brought up, but were not different between one-child families and those with more children.
In this study, the effect of the herbal prescription Tian Ma Gou Teng Yen (TGY), which is traditionally used to treat certain diseases associated with elevated arterial pressure (AP), on the general development of hypertension was investigated in the spontaneously hypertensive rat (SHR). An aqueous extract of TGY was given orally (0.5 ml/100g body weight) to 5 week old SHR twice a day for six consecutive days followed by one day without herbal therapy. The herbal prescription was administered until the SHR were 16 weeks of age. Administration of TGY significantly altered the development and prevented hypertension in SHR. On the other hand, heart rate, body weight, food and water intake, and urine volume and electrolytes were not altered. These data suggest that the effect of TGY on AP was through an action of TGY on sympathetic vasomotor activity.