Search PubMedSearch

Biomedical subjects

T P Wang

Publications and source records attributed to T P Wang.

At least 19 recordsLinked to original sources

Merocyanine 540-sensitized photoinactivation of enveloped viruses in blood products: site and mechanism of phototoxicity.

The amphipathic dye, merocyanine 540 (MC540), which preferentially photosensitizes enveloped viruses and virus-infected cells, is currently being evaluated in preclinical models as a blood sterilizing agent. In this communication, we report on an initial analysis of the site and nature of MC540-mediated photodynamic damages to human herpes simplex virus type 1 and human cytomegalovirus. The comigration of dye molecules and virions on a gel filtration column, the red-shift of the fluorescence emission spectrum of virus-containing fractions, and the distribution of MC540-treated virions in an aqueous two-phase partition system were indicative of MC540 binding to the enveloped viruses and localizing in a lipophilic environment (most likely the viral envelope). Fluorescence quenching and fluorescence resonance energy transfer experiments suggested that both dye monomers and dimers were capable of partitioning into the lipid bilayer of the viral envelope. Adsorption and penetration assays and immunohistochemical analyses of viral antigen expression showed that MC540-sensitized irradiation interfered with early phases of the infectious process, the adhesion to the host cell, the penetration of the host cell, and the translocation of the virus into the nucleus of the host cell. The inactivation of viruses was inhibited if oxygen in the medium was displaced by argon, enhanced if air was displaced by pure oxygen or if water was replaced by deuterium oxide. This suggested that the MC540-sensitized photoinactivation of enveloped viruses is an oxygen-dependent process and that singlet oxygen is one but not necessarily the only mediator of the antiviral effects of MC540.

Animals

A clinical application of artery-including silicone tubing to peripheral nerve defect.

7 cases of 11 peripheral nerve defects (5 median nerves, 5 ulnar nerves, and 1 radial nerve) were repaired through artery-including silicone tubing. The nerves have gaps within 3 cm in 9, and 3 to 5 cm in 2. Repairing the defect's location, 4 of them were below the axilla; 1 at the upper 1/3 part of the forearm and 6 at the lower part of the forearm. The duration of injuries was from 4 to 7 months, except one case lasting over a year. Six patients with 9 nerves involved had adequate follow-up of 6 to 9 months. One patient with 2 nerves was lost to follow-up. The results were excellent in 5 nerves (M4S3), good in 2 (M3S3), and poor in 2 (M1S1).

Adolescent

Psoralens cleave pBR322 DNA under ultraviolet radiation.

Supercoiled (SC) pBR322 was used to probe the recent claim that 5-geranoxylpsoralen (5-GOP) did not photoreact with DNA. Contrary to expectations, 5-GOP was found to damage DNA in the presence of UV-A through two competing pathways: (a) single strand breaks, identified by the conversion of supercoiled into open circular and linear DNA, and (b) cross-linking, revealed by the fluence-dependent decrease in the extent of denaturation of the double stranded supercoiled DNA to single stranded circular DNA. In addition, a fluence-dependent modification reduced the ability of the restriction enzyme EcoR I to linearize the photosensitized DNA, and alkali-labile lesions were generated. Psoralen, 5-methoxypsoralen, and 8-methoxypsoralen, which are well-known to undergo cycloaddition to DNA, had a more pronounced effect on supercoiled DNA. Single strand breaks occurred more readily than with 5-GOP, and the surviving SC form remaining had reduced electrophoretic mobility in agarose gels. In all cases, the DNA damage was more prominent when oxygen was absent.

DNA, Superhelical

Photosensitization by 2-chloro-3,11-tridecadiene-5,7,9-triyn-1-ol: damage to erythrocyte membranes, Escherichia coli, and DNA.

The natural product 2-chloro-3,11-tridecadiene-5,7,9-triyn-1-ol (1) photosensitized the inactivation of Escherichia coli in the presence of near-ultraviolet light (320-400 nm; NUV) under both aerobic and anaerobic conditions. A series of E. coli strains differing in DNA repair capabilities and catalase proficiency exhibited indistinguishable inactivation kinetics following treatment with the chemical plus NUV. The presence of carotenoids did afford some protection to E. coli against inactivation under aerobic conditions, consistent with the involvement of singlet oxygen. The photosensitized hemolysis of human erythrocytes occurred more rapidly in the absence than in the presence of oxygen. Aerobically, the onset of hemolysis was partially inhibited by NaN3 and by 2,6-di-t-butyl-4-methylphenol (BHT) but not by superoxide dismutase (SOD). The aerobic lipid peroxidation observed in the membranes of erythrocyte ghosts was completely inhibited by BHT, and partially by NaN3, but not by SOD. These results suggest that either lipid peroxidation of the membrane is not the main cause of photohemolysis or that BHT has insufficient access to intact erythrocyte lipids to protect them. Aerobically, crosslinking of membrane proteins was also observed; it was not affected by SOD, but was partially inhibited by BHT and NaN3. The anaerobic photosensitized hemolysis of erythrocytes was more rapid; a radical mechanism was suggested since BHT inhibited the hemolysis to a greater extent than under aerobic conditions. Neither lipid peroxidation nor protein crosslinking was observed under conditions believed to be anaerobic. A light-dependent electron transfer to cytochrome c was obtained under argon but not under oxygen. Although induced mutations were not observed in the experiments with E. coli, 1 was capable of damaging both supercoiled pBR322 and Haemophilus influenzae transforming DNA in a manner that seemed to be equivalent under aerobic and anaerobic conditions. In conclusion, 1 can behave as typical photodynamic molecule under aerobic conditions but, in contrast to most photodynamic molecules, it is also phototoxic under anaerobic conditions. The extent to which the radical reactions detected under anaerobic reactions compete with the photodynamic processes when oxygen is present is not known.

Alkadienes

[Relation between left ventricular mass indexes and cardiac function in hypertensive patients: an approach with Doppler echocardiography].

73 age-matched hypertensive patients, 46 men and 27 women, were divided into the four groups according to left ventricular mass indexes (LVMI) and normal control groups were established correspondingly. Doppler and M-mode echocardiography were used to assess the systolic and diastolic functions of left ventricle (LV) and the alterations of heart construction. It was shown that when the LVMI increased slightly, the internal dimension and systolic function of LV had no significant change, but the diastolic function became abnormal and the left atrium enlarged. When the LVMI increased significantly, both the left atrium and left ventricle enlarged and the systolic and diastolic functions of LV were impaired. It is concluded that increase of LV mass may be present in the early stage of hypertension and left atrial enlargement is an early sign of left ventricular diastolic dysfunction, which occurs before systolic dysfunction in the patients with essential hypertension.

Aged

Classification of plasma cortisol patterns in normal subjects and in Cushing's syndrome.

The 24-h pattern of half-hourly sampled plasma cortisol in normal human subjects shows a 24-h (circadian) period, which may be variably distorted in patients who suffer from autonomous hypercortisolism (Cushing's syndrome). We have developed a pattern recognition system for computer classification of cortisol time series into the normal class and subclasses of Cushing's syndrome with different etiology ("pituitary" designating pituitary tumor, "adrenal" designating adrenal tumor, and "ectopic" designating tumor elsewhere). Discriminatory features were extracted from Fourier analysis and Karhunen-Loeve expansion coefficients of cortisol time series. Decision functions were trained by the LMSE algorithm and tested by the jack-knife test procedure on a data-base of 90 normal and patient patterns. The classification accuracy for normal, "pituitary," "adrenal," and "ectopic" classes was 100, 98.1, 98.3, and 100%, respectively. Hence this pattern recognition system may be useful as an aid in the differential diagnosis of Cushing's syndrome.

Algorithms

alpha-Terthienyl photosensitizes damage to pBR322 DNA.

alpha-Terthienyl photosensitizes single strand breaks in pBR322 DNA. Almost identical results were observed under oxygen and under argon. In the presence of oxygen, this DNA nicking was enhanced by histidine and was not affected by superoxide dismutase, catalase, or the antioxidant BHT. Although chemical damage to DNA treated with alpha-terthienyl plus near-UV was clearly demonstrated in vitro, transformation in E. coli with this damaged pBR322 DNA still took place. Likewise, Haemophilus influenzae DNA transforming activity was not significantly decreased by photosensitization with alpha-terthienyl.

DNA Damage

Microsurgical treatment of disorders of leg and foot--a report of 40 cases.

Since 1979, the authors have performed five types of microsurgical flap (including myocutaneous flap) graft to treat 40 patients with disorders of leg and foot. In the treatment of inflammatory diseases, good results were obtained owing to the following important points: 1) the operation was performed with inflammation well controlled or localized, particularly in chronic osteomyelitis; 2) indication for each type of microsurgical flap was made carefully; 3) isolation of flap was carried out gently, bleedings were thoroughly stopped by ligation.

Cicatrix

Light-dependent cytotoxic reactions of anthracene.

Anthracene is a photodynamic compound in vitro. In the presence of oxygen, it is known to generate singlet oxygen and participate in Type II reactions. In aqueous solution, it also participates in Type I reactions, such as in the photoreduction of cytochrome c, which can be suppressed by superoxide dismutase. In argon, direct photoreduction of cytochrome c also takes place. Anthracene induces the photodynamic hemolysis of human erythrocytes and inactivates Escherichia coli cells photodynamically. By using a series of E. coli strains differing in DNA repair capabilities and catalase proficiency, sensitivity to inactivation by anthracene plus NUV was correlated with catalase deficiency rather than with particular repair deficiencies. The fact that carotenoid genes cloned and expressed in E. coli offered partial protection suggests that the membrane may be one possible target for inactivation by anthracene plus NUV. Anthracene plus NUV inactivated Haemophilus influenzae transforming DNA and led to nicking of supercoiled pBR322 DNA in vitro. In vivo, therefore, anthracene is a phototoxic molecule whose cytotoxicity could be the result of damage to more than one target.

Anthracenes

The hemolysis of erythrocytes by singlet oxygen generated in the gas phase.

Many sensitizers cause photodynamic hemolysis of erythrocytes. As these sensitizers usually participate in Type I as well as Type II processes, the determination of the mechanism(s) of photosensitized hemolysis is always ambiguous. Here, human erythrocytes were proved to hemolyze upon treatment with singlet oxygen (1 delta g) generated with fluoranthene in the gas phase. These conditions rigorously exclude the participation of superoxide anion. The standard diagnostic tests for singlet oxygen (enhanced effect in D2O and protection by NaN3) gave the anticipated results when the erythrocytes were treated with 1O2 generated in the gas phase. When the erythrocytes were irradiated in a buffer solution containing fluoranthene, the results of the diagnostic tests depended on the sensitizer concentration.

Hemolysis

Clinical application of the forearm island skin and fascia flap with posterior interosseous artery pedicle--report of 15 cases.

The present paper reported 15 cases, in which skin and fascia forearm island flap with posterior interosseous artery pedicle was applied. It was found that this flap has the advantages of stable vessels, abundance in blood supply and good circulation, without sacrificing the main arteries of the forearm. As a result, it is an ideal method for repair and reconstruction of the hand and forearm.

Adolescent

A simple and rapid solid-phase RNA sequencing method.

A simple and rapid solid-phase RNA sequencing method has been developed based on Peattie's direct chemical method. 3'-Terminally labeled RNA was immobilized on DEAE-cellulose sheets and followed by specific modification with dimethyl sulfate, diethylpyrocarbonate, hydroxylamine (at pH 10 for the uridine and pH 5.5 for the cytidine reaction), and cleavage reaction with aniline. RNA fragments were washed from the DEAE-cellulose sheets using salt solutions, precipitated with ethanol, and separated by 15% polyacrylamide gel electrophoresis. Due to the complete removal of the impurities normally present in the solution method, the higher resolution of the sequencing bands and lower background on the autoradiograph make this solid-phase technique more efficient. This solid-phase technique is much faster and more convenient than the original method.

Animals

Influence of cerebral embolism on brain monoamines.

In baboons the right cerebral hemisphere was embolised by a shower of microemboli, immediately followed by one large embolus designed to occlude the middle cerebral artery (MCA). One hour after embolism a significant, though small, reduction in blood flow and oxygen consumption of the embolised hemisphere was recorded, at which time the animals were killed and brain monoamines measured. Dopamine was reduced in the ipsilateral caudate nucleus, the reported site of maximal ischaemic damage in this model. Dopamine levels were increased in frontal and occipital grey matter sampled from areas surrounding the occluded MCA territory and in similar brain areas of the opposite non-embolised hemisphere. Noradrenaline was increased in grey matter from both cerebral hemispheres, as well as subcortical structures bilaterally. Brain 5-hydroxytryptamine levels were unaltered, but increased 5-hydroxyindoleacetic acid in cisternal cerebrospinal fluid suggested transient alteration in 5-hydroxytryptamine metabolism after embolism. The effects of cerebral embolism on brain monoamine metabolism appear to be different from the effects of permanent surgical occlusion of major cerebral vessels. The bilaterality of effects after unilateral hemispheric embolism might be related to diaschisis. The mechanisms of the observed changes, as well as their relevance to the progression of cerebral ischaemia and the complications associated with cerebral embolism, still require to be established.

Animals

Ischemia-induced seizures and cortical monoamine levels.

Seizure activity as a component of the ischemic process possibly responsible for monoamine changes described in the gerbil stroke model was the subject of this study. Abnormal motor activity suggestive of seizures developed one to three hours after unilateral ligation of the common carotid artery in approximately 50% of gerbils that exhibited signs of stroke. Reduction of cortical levels of dopamine and norepinephrine was observed only when seizures occurred in association with stroke. The levels of 5-hydroxytryptamine were reduced bilaterally in animals with and without signs of stroke and were reduced further in animals with stroke plus seizures. Further study is needed to establish whether the catecholamine changes associated with ischemia-induced seizures are primary and causative or secondary to seizure activity itself. In the ischemic brain, 5-hydroxytryptamine metabolism appears disordered independent of seizure activity. Seizure activity must be taken into account when the mechanisms of disordered monoamine metabolism are being examined in the gerbil stroke model.

Animals