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Biomedical subjects

Y N Wu

Publications and source records attributed to Y N Wu.

At least 19 recordsLinked to original sources

Three- versus four-week administration of benzathine penicillin G: effects on incidence of streptococcal infections and recurrences of rheumatic fever.

OBJECTIVE: To investigate the effects of 3-week versus 4-week administration of benzathine penicillin G (BPG) on the incidence of Group A streptococcal infections and the recurrences of rheumatic fever (RF). STUDY DESIGN: We started, in 1979, randomly allocating all patients with RF to a 3-week or 4-week BPG prophylaxis program. They were examined at the RF clinic, every 3 to 6 months, and at any time they did not feel well. During 1979 to 1989, throat cultures and sera for antistreptolysin O and streptozyme titers were obtained at each clinic visit. Chest radiographs, electrocardiogram, color Doppler echocardiograms, and acute phase reactants were obtained. SUBJECTS: Two hundred forty-nine patients fulfilled the revised Jones criteria and were followed until December 1991: 124 in the 3-week and 125 in the 4-week program. Their age, sex, weight, percentage with history of RF, severity of cardiac involvement, follow-up duration, and compliance to program were comparable. Eight hundred eighty throat cultures were collected in the 3-week program and 770 were collected in the 4-week program. Six hundred sixteen and 627 sera were determined in each program for antistreptolysin O, and 582 and 592 sera for streptozyme titers. RESULTS: True streptococcal infections occurred in both programs: 39 infections in the 3-week program, and 59 infections in the 4-week program (7.5 vs 12.7 per 100 patient-years). Four infections with no antibody response occurred in the 3-week program, and three such infections in the 4-week program. Nine RF recurrences occurred in 8 patients in the 3-week program, and 16 recurrences in 16 patients in the 4-week program. Prophylaxis failure occurred in 2 of 124 patients in the 3-week program, and in 10 of 125 patients in the 4-week program (0.25 vs 1.29 per 100 patient-years). The overall recurrences/infections rate in each program was comparable, 13.6% vs 15.5%, but the recurrences/ infections rate due to prophylaxis failure was higher in the 4-week program than in the 3-week program, 3.0% versus 9.7%. CONCLUSIONS: This 12-year prospective and controlled study documented that streptococcal infections and RF recurrences occurred more often in the 4-week program than in the 3-week program. The risk of prophylaxis failure was fivefold greater in the 4-week program than in the 3-week program.

Adolescent

Presynaptic inhibition of gamma-aminobutyric acidB-mediated synaptic current by adenosine recorded in vitro in midbrain dopamine neurons.

Adenosine receptor antagonists such as caffeine cause dopamine-dependent behavioral arousal and hyperlocomotion in rodents. In the present study, we used the whole-cell recording technique in the rat brain slice to investigate effects of adenosine on dopamine neurons and their synaptic inputs in the substantia nigra zona compacta and ventral tegmental area. Adenosine was most potent for inhibiting the amplitude of the inhibitory postsynaptic current (IPSC) mediated by gamma-aminobutyric acid (GABA)B receptors (EC50 = 47 +/- 3 microM) compared with inhibition of the GABAA-mediated IPSC (117 +/- 51 microM) and the excitatory amino acid-mediated excitatory postsynaptic current (119 +/- 36 microM). Adenosine failed to inhibit current evoked by exogenous GABA or baclofen, suggesting that adenosine acted presynaptically to reduce GABA release from nerve terminals. Adenosine inhibited the GABAB-mediated IPSC by acting at the adenosine A1 receptor, because its effect was blocked by the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (100 nM), as well as by the methylxanthines caffeine (1 mM) and theophylline (300 microM). The rank-order of potency of adenosine agonists [N6-cyclohexyladenosine > R-(-)-N6-(2-phenylisopropyl)-adenosine = N6- cyclohexyladenosine > 5'-N-ethylcarboxamidoadenosine > 2-chloroadenosine] also was consistent with activation of the adenosine A1 receptor, whereas the selective adenosine A2A agonist CGS 21680 [2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine] had no effect on the GABAB IPSC. None of the adenosine agonists or antagonists affected holding current or membrane conductance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine

RNase inhibition of human immunodeficiency virus infection of H9 cells.

Onconase and bovine seminal RNase, two members of the RNase A superfamily, inhibit human immunodeficiency virus type 1 replication in H9 leukemia cells 90-99.9% over a 4-day incubation at concentrations not toxic to uninfected H9 cells. Two other members of the same protein family, bovine pancreatic RNase A and human eosinophil-derived neurotoxin, have no detectable antiviral activity, demonstrating a strikingly selective antiviral activity among homologous ribonucleases. The antiviral RNases do not appear to affect viral particles directly but inhibit replication in host cell cultures. Onconase, already in clinical trials for cancer therapy, and bovine seminal RNase have potential as antiviral therapeutics.

Animals

Control of cationic amino acid transport and retroviral receptor functions in a membrane protein family.

A partial cDNA sequence indicated that the T lymphocyte early-activation gene (Tea) encodes a protein related to the dual-function ecotropic retrovirus receptor/cationic amino acid transporter (ecoR/CAT1), and RNA blots suggested highest Tea expression in T lymphocytes and liver (MacLeod, C.L., Finley, K., Kakuda, D. Kozad, C.A., and Wilkinson, M.F. (1990) Mol. Cell. Biol. 7, 3663-3674). The sequence of full-length Tea cDNA from liver (3683 bases) predicts a 657-amino-acid protein (CAT2 alpha) with 12-14 transmembrane domains. A long (515 base) region with six initiation codons and termination codons precedes the translation start codon. The liver Tea cDNA is identical to Tea cDNA from T lymphocytes (encoding CAT2 beta) with the exception of an apparent alternatively spliced sequence encoding a hydrophilic loop of 43 amino acids. The liver-specific sequence contains unique consensus sites for phosphorylation by cyclic AMP-dependent protein kinase and by protein kinase C. Injection of Xenopus oocytes with CAT2 alpha or CAT2 beta messenger RNA resulted in expression of Na(+)-independent cationic amino acid transport that was detected by current measurements under voltage-clamp. Although the amino acid sequences of the isoforms differ in only 21 of 43 residues with the majority of substitutions being conservative, the apparent affinity of CAT2 beta for arginine uptake was 70-fold higher than the CAT2 alpha isoform (Km 38 microM versus 2.7 mM). Neither isoform functioned as a receptor for ecotropic or amphotropic murine retroviruses. However, CAT1-CAT2 chimeric proteins that contain the first three putative extracellular loops of ecoR/CAT1 functioned as ecotropic receptors despite a diminished capacity to bind the viral envelope glycoprotein. The chimeric proteins also functioned as basic amino acid transporters with substrate affinities corresponding to the CAT2 isoform constituting the carboxyl-terminal portion. These results demonstrate that domains of these transporters can function in chimeric combinations to control viral receptor and transport functions.

Amino Acid Sequence

Long-term outcome of patients with rheumatic fever receiving benzathine penicillin G prophylaxis every three weeks versus every four weeks.

OBJECTIVE: To compare the efficacy of injections of 1.2 million units of benzathine penicillin G given every 3 weeks versus every 4 weeks for secondary prevention of rheumatic fever, based on the long-term outcome of patients receiving such prophylaxis. METHODS: A total of 249 consecutive patients with rheumatic fever, randomly assigned to either a 3-week or a 4-week regimen, were examined every 3 to 6 months, and followed for 794 and 775 patient-years, respectively. RESULTS: Compliance with each regimen was comparable: 83 (66.9%) of 124 patients in the 3-week group versus 92 (73.6%) of 125 patients in the 4-week group stayed in the program (p > 0.05). Streptococcal infections occurred less frequently in those receiving the 3-week regimen: 7.5 versus 12.6 per 100 patient-years (p < 0.01). Prophylaxis failed in 2 patients receiving the 3-week regimen and in 10 receiving the 4-week regimen (0.25 and 1.29 per 100 patient-years respectively; p = 0.015). Serum penicillin levels were adequate (> or = 0.02 micrograms/ml) in 100 (56%) of 179 samples obtained 21 days after penicillin injection in the 3-week regimen, and in 51 (33%) of 155 samples obtained 28 days after injection in the 4-week regimen (p < 0.01). Of 71 patients with mitral regurgitation in the 3-week regimen, 47 (66%) no longer had the murmur; of 87 patients in the 4-week regimen, 40 (46%) no longer had the murmur (p < 0.05). CONCLUSIONS: This 12-year controlled study indicates that the outcome of patients with rheumatic fever is better with a 3-week than with a 4-week penicillin prophylaxis regimen. Greater emphasis and more widespread use of the 3-week regimen should be recommended.

Adolescent

Retinoic acid disrupts the Golgi apparatus and increases the cytosolic routing of specific protein toxins.

All-trans retinoic acid can specifically increase receptor mediated intoxication of ricin A chain immunotoxins more than 10,000 times, whereas fluid phase endocytosis of ricin A chain alone or ricin A chain immunotoxins was not influenced by retinoic acid. The immunotoxin activation by retinoic acid does not require RNA or protein synthesis and is not a consequence of increased receptor binding of the immunotoxin. Vitamin D3 and thyroid hormone T3, that activate retinoic acid receptor (RAR) cognates, forming heterodimers with retinoid X receptor (RXR), do not affect the potency of immunotoxins. Among other retinoids tested, 13-cis retinoic acid, which binds neither RAR nor RXR, also increases the potency of the ricin A chain immunotoxin. Therefore, retinoic acid receptor activation does not appear to be necessary for immunotoxin activity. Retinoic acid potentiation of immunotoxins is prevented by brefeldin A (BFA) indicating that in the presence of retinoic acid, the immunotoxin is efficiently routed through the Golgi apparatus en route to the cytoplasm. Directly examining cells with a monoclonal antibody (Mab) against mannosidase II, a Golgi apparatus marker enzyme, demonstrates that the Golgi apparatus changes upon treatment with retinoic acid from a perinuclear network to a diffuse aggregate. Within 60 min after removal of retinoic acid the cell reassembles the perinuclear Golgi network indistinguishable with that of normal control cells. C6-NBD-ceramide, a vital stain for the Golgi apparatus, shows that retinoic acid prevents the fluorescent staining of the Golgi apparatus and eliminates fluorescence of C6-NBD-ceramide prestained Golgi apparatus. Electron microscopy of retinoic acid-treated cells demonstrates the specific absence of any normal looking Golgi apparatus and a perinuclear vacuolar structure very similar to that seen in monensin-treated cells. This vacuolization disappears after removal of the retinoic acid and a perinuclear Golgi stacking reappears. These results indicate that retinoic acid alters intracellular routing, probably through the Golgi apparatus, potentiating immunotoxin activity indepedently of new gene expression. Retinoic acid appears to be a new reagent to manipulate the Golgi apparatus and intracellular traffic. As retinoic acid and immunotoxins are both in clinical trials for cancer therapy, their combined activity in vivo would be interesting to examine.

4-Chloro-7-nitrobenzofurazan

Detection of varicella-zoster virus DNA in air samples from hospital rooms.

Varicella-zoster virus (VZV) is a highly contagious infectious agent that causes outbreaks in institutional settings. Transmission of VZV is felt to occur following direct contact with an infected individual and by aerosol spread. To document the aerosolization of VZV, a polymerase chain reaction (PCR) assay was used to detect VZV DNA in air samples obtained from hospital rooms of patients with active VZV infection. VZV DNA was detected in 64 (82%) of 78 air samples from rooms housing patients with active varicella and 9(70%) of 13 samples from rooms of patients with herpes zoster. VZV was detected 1.2-5.5 m from patients' beds and for 1-6 days following onset of rash. On some occasions, VZV DNA could be detected outside the hospital isolation rooms housing patients. This PCR-based method allows the detection and semiquantitation of VZV aerosolization and can be a useful tool for monitoring efforts to control VZV aerosols in the environment.

Adolescent

[Conservative therapy of combining laparoscopy and Chinese medicine for ectopic pregnancy].

44 cases of ectopic pregnancy have been treated conservatively by combining laparoscopy with TCM and all were successful. After confirmatory diagnosis was made under laparoscope low dose (5-15mg) of Methotrexate (MTX) was injected into tubal swelling, as well as taking modified Huo-Luo-Xiao-Ling Dan orally and using Ding-Tong paste and Zi-Gong pill externally, it not only improved the function of herbal medicine that was not potent enough to kill active embryo, but also gave full play of TCM which could remove stasis and masses by promoting blood circulation to assist in killing the embryo. The successful rate (100%) of combined therapy was significantly higher than that (78.2%) of control group (using TCM only, P < 0.01). Comparing with the two groups in successful cases, the mean serum hCG concentrations per day of combined therapy lowered faster than that of control group (P < 0.005), the mean time of abdominal pain disappearance and hospitalized period of combined group were shorter (P < 0.01). In a word, this combined therapy is a simple and safe method which could preserve reproductive function to the maximum.

Adult

The blocking effect of phenolic acid on N-nitrosomorpholine formation in vitro.

Phenolic acids (PAs) are widely found in many daily consumed vegetables and fruits. The inhibitory effects of PAs on N-nitrosomorpholine (NMOR) formation in vitro under simulated gastric juice condition were studied. The results showed that the inhibitory potency of thirteen varieties of PAs differed greatly, which may be related to their chemical structures; the blocking rate (BR) of different kinds of PAs were as follows: caffeic acid, 92.5%; tannic acid, 90.0%; gallic acid, 86.8%; sinapinic acid, 86.2%; ferulic acid, 81.1%; chlorogenic acid, 69.4%; gentisic acid, 69.2%; syringic acid, 62.1%; protocatechuic acid, 56.0%; p-coumaric acid, 52.5%; vanillic acid, 35.4%; moreover, p-hydroxybenzoic acid and m-coumaric acid had the least blocking effect or even slight catalyzing effect. The results also demonstrated that amounts of NMOR formed were negatively correlated with molar ratio of PAs to nitrite and that the optimum pH for inhibition was between 2 and 3.

Carcinogens

Implication of aneurysmal transformation in isolated perimembranous ventricular septal defect.

Defects on the membranous ventricular septum (perimembranous ventricular septal defect [VSD]) may spontaneously close or diminish in size by "aneurysmal transformation" (i.e., adherence of the tricuspid valve or adjacent tissue onto the VSD). It was recently shown that the appearance of aneurysmal transformation may be associated with subaortic ridges, as well as left ventricular (LV)-to-right atrial (RA) shunts. In all, 877 consecutive patients with isolated perimembranous VSD were retrospectively studied. Results of actuarial analysis showed that patients with a perimembranous VSD had a 98% probability of aneurysmal transformation by the age of 240 months. Of these patients, the expected probabilities of developing LV-RA shunt, spontaneous closure and subaortic ridge were 45, 35 and 6%, respectively. Patients with LV-RA shunts had higher probabilities of developing infective endocarditis (p = 0.002) and persistent left-to-right shunts (p < 0.001). The presence of a subaortic ridge may be accompanied by LV outflow tract obstruction (10 of 25 patients), infundibular pulmonary stenosis (n = 3), or aortic valve deformity or aortic regurgitation (n = 5), and none of those with a subaortic ridge closed spontaneously. It was confirmed that a substantial proportion of aneurysmal transformation of isolated perimembranous VSD is associated with LV-RA shunts and subaortic ridges.

Age Factors

Cloning and expression of a human neutral amino acid transporter with structural similarity to the glutamate transporter gene family.

A cDNA was isolated from human brain that encodes an amino acid sequence 34-39% identical to previously published glutamate transporter sequences. Injection of RNA transcribed from this cDNA into Xenopus oocytes resulted in expression of a transport activity with the properties of the neutral amino acid uptake system ASC. Superfusion of alanine, serine, and cysteine evoked sodium-dependent inward currents in voltage-clamped oocytes expressing the transporter. These currents were dose-dependent, stereospecific, and saturable, with Km values ranging from 29 to 88 microM. Northern blot analyses revealed ubiquitous expression of this gene, termed ASCT1, consistent with the general metabolic role ascribed to system ASC.

Amino Acid Sequence

High performance liquid chromatographic determination of phenolic acids in fruits and vegetables.

A simple isocratic HPLC technique has been developed for the quantitative analysis of phenolic acids (PAs) in fruits and vegetables. Nine benzoic and cinnamic acid derivatives were separated in less than 30 min, and the resolution was all more than 1.23. The ranges of linearity for PAs standards were 0.2-100 ng, even up to 600 ng (r = 0.983-1.000) and the detection limits were 0.02-0.24 mg/kg. Samples of fresh vegetables and fruits were extracted with 80% methanol and ethyl acetate, then purified with C18 Sep-Pak cartridge and determined by HPLC. This method was applied to the determination of PAs in 7 kinds of fruits and vegetables, i.e., apple, pear, Chinese cabbage, cauliflower, turnip, soybean sprout and white grape wine. The content of the 9 PAs varied widely in the 7 kinds of foods studied. The average concentrations of chlorogenic acid in apple (100.2 mg/kg) and pear (30.8 mg/kg) were quite high, and sinapinic acid was remarkable (42.5 mg/kg) in Chinese cabbage, and protocatechuic acid had the highest concentration of all the PAs in white wine.

Chromatography, High Pressure Liquid

[Clinical evaluation of the ultrasonic root canal instrumentation].

Five hundred and fifty-nine teeth from 432 patient' were divided randomly into the ultrasonic or the hand root canal instrumentation group. The results are shown as follows: Less instrumentation time was needed significantly in the ultrasonic group (anterior tooth: 2.37 +/- 1.37 minutes, posterior tooth: 5.33 +/- 2.83 minutes) than in the hand group (anterior tooth: 3.15 +/- 2.43 minutes, posterior tooth: 8.42 +/- 4.64 minutes); The rate of instrument fracture in the ultrasonic group (5.28%) was significantly lower than in the hand group (10.97%); No significant difference both in the rate of postoperative pain within 1 week after root canal instrumentation and the 1 year treatment effective rate were found between two groups.

Adolescent

The inhibitory effect of Chinese tea and its polyphenols on in vitro and in vivo N-nitrosation.

The objective of this study is to evaluate the possible role of Chinese tea as a natural inhibitor of N-nitrosation, and to compare the relative inhibitory potency of various kinds of Chinese tea in vitro and in vivo. Studies on the inhibitory effect of 145 samples of Chinese tea on the formation of N-nitrosomorpholine (NMOR) showed that the inhibitory potency of the 7 types of Chinese tea differed greatly, the average blocking rate of green tea (89.04%, n = 60), crush, tear, and curl (CTC) black tea (86.99%, n = 13), brick tea (85.40%, n = 7), jasmine tea (84.99%, n = 21), Oolong tea (82.37%, n = 9), sun-dried tea (61.99%, n = 13) and Chinese Gongfu black tea (54.98%, n = 22), were positively correlated with their polyphenols contents. The inhibitory effect of green tea and black tea on endogenous N-nitrosation was also confirmed in 3 human volunteer experiments. Drinking tea after meal had a greater effect than drinking it before meal. It is concluded that Chinese tea can exert a relatively strong inhibitory potency for N-Nitroso compounds (NOC) formation both in vitro and in humans, and the active constituents may be related to their polyphenols contents, especially the tea catechin derivatives. The results also demonstrated that the amounts of NMOR formed in vitro depended on the molecular structure of tea catechin derivatives and their molar ratios to nitrite.

Adult

Cytotoxic ribonucleases and chimeras in cancer therapy.

Ribonucleases serve as cytotoxic agents during host defense and physiological cell death pathways. In bacteria, higher plants, and mammals, ribonucleases appear to bind cells, enter the cytosol where they degrade RNA, and kill the target cell. This process functions in interstrain competition in bacteria, in the death of incompatible pollen in higher plants, and likely plays a role in the antiparasitic and anticancer activity of eosinophils in man. One can alter the target cell specificity of RNases by coupling them to new cell-binding domains. Chemically coupling RNases to new binding moieties or fusing RNase genes to antibody genes results in chimeric molecules with specified cell-type cytotoxicity. Thus, one can target one's own host defense cytotoxins to select cell populations. This allows the use of human proteins, instead of plant and bacterial toxins, in the construction of immunotoxins. RNases also can be engineered to kill cells by cytosolic expression or to kill viruses by packaging into viruses. Engineering RNases into cell-type-specific cytotoxins may result in a new class of therapeutic reagents. We review a number of interesting physiological cell cytotoxicity pathways utilizing RNases and then describe the recent results on engineering RNases for therapeutic use.

Amino Acid Sequence

Anti-(14-3-3 protein) antibody inhibits stimulation of noradrenaline (norepinephrine) secretion by chromaffin-cell cytosolic proteins.

Incubation of digitonin-permeabilized bovine chromaffin cells in the absence of Ca2+ results in a loss of both cytosolic proteins and Ca(2+)-dependent secretion. Addition of these leaked proteins prevents this loss of secretory activity. We have purified a protein from an extract of bovine adrenal medulla which can partially prevent this loss of Ca(2+)-dependent secretion. Antibody against this protein inhibited the ability of leaked chromaffin-cell proteins to prevent the loss of Ca(2+)-dependent secretion. Sequence analysis showed it to have sequence identity with bovine brain 14-3-3 protein. These results demonstrate that 14-3-3 protein makes a significant contribution to the ability of leaked chromaffin-cell proteins to maintain secretory activity.

14-3-3 Proteins

Modification of chromaffin cells with pertussis toxin or N-ethylmaleimide lowers cytoskeletal F-actin and enhances Ca(2+)-dependent secretion.

In an attempt to identify proteins involved in the secretory response, bovine chromaffin cells were modified with N-ethylmaleimide (NEM). NEM concentrations less than 30 microM enhanced norepinephrine secretion evoked by nicotine or by K+ depolarization and increased Ca(2+)-dependent secretion from digitonin-permeabilized cells. Higher concentrations of NEM inhibited secretion. The protein modified by NEM which was responsible for the enhancement of secretory activity appeared to rapidly diffuse out of the digitonin-permeabilized cells. When proteins which diffuse from control digitonin-permeabilized cells were incubated with pertussis toxin and [32P]NAD, several proteins were ADP-ribosylated. However, when proteins from cells preincubated with 30 microM NEM were incubated with pertussis toxin and [32P]NAD, these GTP-binding proteins (G-proteins) were not ADP-ribosylated, which suggests that they were modified in the cell by NEM. Stimulation of norepinephrine secretion by NEM was not additive with that caused by pertussis toxin. Modification of chromaffin cells with pertussis toxin or with 30 microM NEM caused a 40-50% decrease in the amount of cytoskeletal F-actin. This decrease in cytoskeletal F-actin may account for the increase in secretory activity.

Actins