Search PubMedSearch

Biomedical subjects

G J Wang

Publications and source records attributed to G J Wang.

At least 19 recordsLinked to original sources

Identification of a Fab interaction footprint site on an icosahedral virus by cryoelectron microscopy and X-ray crystallography.

Biological processes frequently require the formation of multi-protein or nucleoprotein complexes. Some of these complexes have been produced in homogeneous form, crystallized, and analysed at high resolution by X-ray crystallography (for example, see refs 1-3). Most, however, are too large or too unstable to crystallize. Individual components of such complexes can often be purified and analysed by crystallography. Here we report how the coordinated application of cryoelectron microscopy, three-dimensional image reconstruction, and X-ray crystallography provides a powerful approach to study large, unstable macromolecular complexes. Three-dimensional reconstructions of native cowpea mosaic virus (CMPV) and a complex of CPMV saturated with a Fab fragment of a monoclonal antibody against the virus have been determined at 23 A resolution from low-irradiation images of unstained, frozen-hydrated samples. Despite the nominal resolution of the complex, the physical footprint of the Fab on the capsid surface and the orientation and position of the Fab have been determined to within a few ångstroms by fitting atomic models of CPMV4 and Fab (Kol)5 to reconstructed density maps.

Antibodies, Monoclonal

Long-term frontal brain metabolic changes in cocaine abusers.

Neurological complications from cocaine use are well recognized. We propose that chronic cocaine use can also cause clinically silent brain dysfunction. We investigated brain glucose metabolism with positron emission tomography (PET) and 2-deoxy-2[18F] fluoro-D-glucose (FDG) in 21 neurologically intact chronic cocaine abusers (C) and 18 normal controls (N). The cocaine abusers were tested 1-6 weeks after the last use of cocaine and seven were retested after a 3 month drug-free period. Global cerebral glucose metabolism was not significantly different between controls and cocaine abusers (N = 38.4 +/- 3, C = 36.5 +/- 5 mumol/100 g of tissue, min). However, cocaine abusers had significantly (P less than 0.05) lower metabolic activity in 16 of the 21 left frontal regions and 8 of the 21 right frontal regions. These decreases persisted after 3-4 months of detoxification and were correlated with the dose (P less than or equal to 0.01) and the years of cocaine use (P less than or equal to 0.05). This study shows reduced rates of frontal metabolism in neurologically intact cocaine abusers that persist even after 3-4 months of detoxification.

Adult

Alcohol intoxication does not change [11C]cocaine pharmacokinetics in human brain and heart.

There is increasing evidence that the combined use of cocaine and alcohol produces enhanced behavioral and toxic effects. We have used PET and tracer doses of [11C]cocaine in 7 normal human volunteers to assess if the distribution and clearance of cocaine are altered by alcohol intoxication. Each subject received 2 PET studies with [11C]cocaine (3-11 micrograms), one before and one during alcohol intoxication (1 g/kg). Regions of interest included the brain (n = 3) and heart (n = 4). Arterial plasma was assayed for unchanged cocaine and for labeled cocaethylene, a metabolite of cocaine found in individuals using cocaine and alcohol in combination (Hearn et al., 1991a). Alcohol intoxication did not change uptake and clearance or the steady-state distribution volume of [11C] cocaine in brain (striatum, thalamus, and cerebellum) or in heart. Moreover, labeled cocaethylene was not detected in the 10 minute plasma sample. These results suggest that the acute enhancement of behavior and toxicity associated with the combined use of cocaine and alcohol is not due to an alteration in cocaine's organ distribution or to cocaethylene formation but may be related to an additive effect resulting from the direct actions of each of these drugs.

Adult

Effect of light scatter on the pattern reversal visual evoked response: comparison with psychophysical results.

The effect of light scatter on the pattern reversal visual evoked response (PVER) was studied in 6 normal subjects. The results were compared with contrast visual acuity, contrast sensitivity function, and glare disability. Light scatter was induced by translucent acrylic sheets. Visual acuity measured with the low-contrast charts decreased significantly (P < 0.0001) even with a small degree of light scatter. Contrast sensitivity decreased with a small degree of light scatter especially for high spatial frequencies. PVER amplitudes decreased especially at the smaller checks with its peak shifted to larger checks. PVER was equally sensitive to light scatter compared to psychophysical tests.

Adult

Mechanical failure of hydroxyapatite- and polysulfone-coated titanium rods in a weight-bearing canine model.

Three types of material that have shown potential as coatings for orthopaedic implants were studied. Using a weight-bearing canine model, Ti-6A1-4V femoral intramedullary rods coated with (1) sintered titanium beads, (2) plasma-sprayed hydroxyapatite, and (3) silyl coupled polysulfone beads were evaluated for mechanical strength and bone ingrowth. The model was designed to secure optimal prosthetic stability by obtaining maximal bony ingrowth during an initial non-weight-bearing phase, then stressing the implant during a full-weight-bearing phase. None of the rods coated with titanium beads failed. All 17 polysulfone-coated rods failed, 13 of them at the interface between the polysulfone coating and the titanium core. Of 18 rods coated with hydroxyapatite, 15 suffered implant breakdown at the interface between the hydroxyapatite coating and the titanium core. This may be due to dissolution of the plasma-sprayed hydroxyapatite in vivo. Testing of retrieved specimens from both hydroxyapatite- and polysulfone-coated implants showed that the shear strength at the coating-rod interface had decreased to less than 40% of the shear strength at manufacture. Despite mechanical failure, histologic study showed extensive bone ingrowth or apposition onto both the polysulfone and hydroxyapatite coatings.

Animals

Contrast visual acuities in cataract patients. I. Comparison with normal subjects.

Contrast sensitivity and glare sensitivity are often abnormal in cataract patients. However, despite significant subjective complaints, relatively good visual acuities often are obtained with high-contrast optotypes. Using Variable-Contrast Visual Acuity Charts (VCVAC), we measured visual acuities of 40 eyes of 24 normal subjects (visual acuity greater than or equal to 1.0) aged 41 to 72 years, and 40 eyes of 28 cataract patients (visual acuity greater than or equal to 0.6) aged 44 to 81 years. The VCVAC consists of 4 different charts (1-4). The contrast is 90% in charts 1 and 4, 15% in chart 2 and 2.5% in chart 3. Chart 4 is the reverse polarity of chart 1. The decrease of visual acuity compared with the high-contrast chart (chart 1) was larger in the cataract group with both in the 15% contrast (0.52 vs. 0.71 octave) and the 2.5% contrast (1.21 vs. 1.75 octaves). In cataract group, 23/40 eyes (57.5%) showed better visual acuity with chart 4 than that of chart 1. In addition to high-contrast optotypes, acuity measurements using intermediate- to low-contrast optotypes, combined with the reverse polarity chart, seem effective in analyzing the visual disabilities caused by early cataract.

Adult

Decreased brain metabolism in neurologically intact healthy alcoholics.

OBJECTIVE: The extent to which cerebral dysfunction in alcoholics is related to the direct effects of alcohol in the brain rather than to indirect mechanisms and/or alcohol withdrawal remains unclear. The purpose of this study was to evaluate whether healthy alcoholics with no evidence of alcohol-associated complications showed changes in brain glucose metabolism. METHOD: Positron emission tomography and [18F]-fluorodeoxyglucose were used to measure regional brain metabolism. The study group consisted of 22 normal, healthy, right-handed volunteers and 22 neurologically intact, healthy, right-handed alcoholics tested 6 to 32 days after alcohol discontinuation. RESULTS: Alcoholics showed significantly lower whole brain metabolism than normal control subjects. Normalization of regional metabolic values to the whole brain metabolic rate revealed that the left parietal and right frontal cortices were the most affected regions. Although the whole brain metabolic rate was correlated with the amount of time since alcohol discontinuation, the "normalized" decreases in left parietal and right frontal glucose metabolism were not. CONCLUSIONS: These findings support the contribution of the direct effect of alcohol as well as alcohol withdrawal on the changes in regional brain metabolism seen in alcoholics. They also provide evidence of cerebral changes in neurologically intact healthy alcoholics.

Adult

A comparison of magnetic resonance imaging to bone scintigraphy in early traumatic ischemia of the femoral head.

In adult rabbits, a unilateral subcapital osteotomy of the femoral neck was performed to induce avascularity. One half of the osteotomy sites were fixed with a magnetic resonance imaging (MRI) compatible absorbable pin and the other osteotomies had no fixation. The femoral heads were studied at three, five, and 12 days with roentgenographs, bone scintigraphy, and MRI, and MRI only at four weeks and six weeks after osteotomy. Histologic studies were performed after imaging to evaluate the viability of the femoral heads. At three, five, and 12 days after osteotomy, bone scintigraphy showed a decrease in uptake of radioisotope in the region of the femoral head on the operated side relative to the acetabulum and greater trochanter in 17 of 18 rabbits. A comparison of the surgically treated hip to the normal hip in fixed and unfixed osteotomies showed no change in the signal behavior of T1- or T2-weighted images in all rabbits Days 3, 5, and 12 (n = 18) after operation. The rabbit femoral heads with fixation of the osteotomy 28 days after operation showed a decrease in signal intensity in the subcapital region of the femoral head. Six weeks after operation, the fixed femoral head shows a loss of signal in a portion of the femoral head near the osteotomy. The MRI signal intensity appears to increase in the unfixed femoral heads six weeks after operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Distribution and kinetics of carbon-11-cocaine in the human body measured with PET.

The extent to which the toxic properties of cocaine are related to its accumulation in various organs is not known. This study investigates cocaine uptake in the human body using 11C-cocaine and PET in 14 healthy males. The rate of uptake and clearance of 11C-cocaine varied among organs: peak uptake occurred in the lungs at 45 sec, in the heart and kidneys at 2-3 min, in the adrenals at 7-9 min, and in the liver at 10-15 min. Half-peak clearances were 90 sec in the lungs, 10 min in the heart and kidneys and 22 min in the adrenals. Liver radioactivity plateaued 10-15 min after injection and remained constant thereafter (40 min). Lung radioactivity paralleled that of plasma. The average uptake at peak was 0.007% (s.d., 0.001) dose/cc in the heart, 0.014% (s.d., 0.002) dose/cc in the kidney, 0.014% (s.d., 0.002) dose/cc in the liver and 0.034% (s.d., 0.001) dose/cc in the adrenals. The significant accumulation of cocaine in human heart, kidneys, adrenals and liver could contribute to its toxicity.

Adult

Structural variation of La Crosse virions under different chemical and physical conditions.

La Crosse (LAC) virions exposed to different pHs (7.3, 6.2, and 5.4) and temperatures (37 degrees, 20 degrees, and 4 degrees) were preserved in thin layers of vitreous ice and observed by electron cryomicroscopy. Our results indicate that, at lower pH, virus particles interact with each other to form aggregates. In some cases, particles could be interpreted to have fused together. At neutral pH and higher temperatures morphological changes consistent with deformation in some particles were observed. We suggest that low pH conditions are sufficient for membrane fusion events to occur with LAC virions.

Animals

A monoclonal antibody reacting with platelets for monitoring thrombolysis.

Thrombus immunoscintigraphy with radiolabeled monoclonal antibodies are presently undergoing intense clinical evaluations. Reports on clinical trials of radiolabeled antifibrins are very encouraging and results of antiplatelet antibody evaluations are forthcoming. Animal studies with antiplatelet antibodies indicate that a diagnosis can be made within the critical "lytic window" of 4-6 h, and thus the imaging procedure may be used as an adjunct to thrombolytic therapy, i.e. screening of patients. We now report on a potentially new application of monoclonal antibodies, immunoimaging for monitoring thrombolysis. In vitro studies were performed with "standardized clots" incubated with 99mTc 50H.19 and re-incubated with streptokinase (SK), urokinase (UK) or recombinant tissue plasminogen activator (rt-PA). The decrease in clot-bound 99mTc 50H.19 activity after SK, UK or rt-PA incubation was proportional to the decrease in clot weight (r = 0.90-0.98). The direct effects of these thrombolytic agents on the labeled antibody and the possible interference of aspirin, warfarin and heparin in thrombus immunoimaging were also investigated. Aspirin, heparin and warfarin did not interfere with clot-binding of 99mTc 50H.19. Thrombolytic agents did not affect the stability of the radiolabel or immunoreactivity of 50H.19. These results indicate that 99mTc 50H.19 is a promising agent that may enable monitoring thrombolysis in addition to thrombus immunoimaging.

Antibodies, Monoclonal

A convenient method of measuring the thermal conductivity of biological tissue.

The basic principle of the thermal conductivity probe is described. Thin probes were developed based on this principle, with a reproducibility of 5.3% and relative error less than 6.0%. Each measurement can be completed in 90 s and the temperature increase can be controlled within 2 degrees C. Using the probes, the thermal conductivities of pig fat, meat, liver, kidney and live and dead snake head were measured and it was found that water content plays an important role in influencing the magnitude of the thermal conductivity of biological tissues. The probe can be used over a temperature range from -40 to 150 degrees C.

Adipose Tissue

A new set of variable-contrast visual acuity charts.

Using a computer plotting technique, we designed four variable-contrast visual acuity charts. The contrast of the first 3 is 90, 15, and 2.5%, respectively. The fourth is 90%, but the luminance of the optotypes and background are the reverse of the first chart. The main features of these charts are as follows. Both contrast sensitivity and spatial frequency are in geometric gradation, which observes the laws of Weber and Fechner. The mean average luminance, (Lmax + Lmin)/2, is constant for all four charts, which follows the concept of contrast sensitivity function (CSF). Charts 1 and 4, which have the same contrasts but different glare backgrounds, measure the glare that is related to the transparency of the refractive media of the eye. Because the charts are rotatable, patient memorization and guessing are minimized. Results compared with those of the conventional visual acuity test and are understandable by patients and eye care practitioners. The charts, which are simple, easy, and require little time, are inexpensive and portable.

Adult

Morphometric diagnosis of bladder tumor.

This paper reports the morphometric analysis results of 100 cases of bladder tumor cells with a Q-900 computer-assisted image analysis system. According to the nuclear area, axis ratio and area ratio of tumor nuclei, bladder transitional cell tumors were divided into 4 grades. This system is called the morphometric grading system (M grading). The results show that the higher the M grading, the lower the survival rate and the higher the recurrence rate. As the M grade increases the tumors could be accompanied by muscular invasion. When recurring, the tumor has a poor prognosis if M grading increases. We conclude that the morphometric grading system is able to yield a quantitative pathologic diagnosis and can predict the biological behavior of bladder tumors. Recently, new techniques for diagnosing and predicting the biological behavior of bladder tumors have been developed. One such technique is morphometric analysis of bladder transitional cell carcinoma with computer-assisted image instruments [1]. Because this morphometric method is easily applicable to pathological section routinely stained with HE and the results are reproducible and more objective, the studies about morphometric analysis of bladder tumor have increased in recent times. This paper reports the preliminary morphometric analysis results of bladder tumor cells examined by a Q-900 image analysis instrument for 100 cases.

Follow-Up Studies

[Effects of alpha-dimethylamino-cyclohexoxyl-dimethyl gallium on ultrastructure of erythrocytic stage of Plasmodium berghei and P yoelii].

The effects of alpha-dimethylamino-cyclohexoxyl-dimethyl gallium (DCDG), a new antimalarial drug developed in China, on the ultrastructure of murine malaria parasites in vivo was studied in comparison with those of chloroquine (CQ) and artemisinin (Art). All these 3 antimalarials were administered ig to mice at dosages of 1-3, 40-80, and 200-400 mg.kg-1 for DCDG, CQ, and Art respectively, based on a similar intensity of morphological changes in the parasites. Blood samples were collected for electron microscopy from 15 min to 48 h after medication. The results showed that DCDG killed the malaria parasites (both asexual and sexual forms) rapidly. The most prominent changes in DCDG-treated parasites were serious dilation of perinuclear space, endoplasmic reticulum, mitochondrion and some other vesicles or intermembranous spaces. These led to the formation of large autophagic vacuoles containing some membranous materials, which were subsequently extruded. Then the parasite cells became more concentrated, finally pyknotic and died. The mode of action was very different from that of CQ and Art.

Animals

Imaging of cocaine-induced global and regional myocardial ischemia.

Severe and often fatal cardiac complications have been reported in cocaine users with narrowed coronary arteries caused by atherosclerosis as well as in young adults with normal coronaries. We have found that in normal dogs cocaine induces severe temporary hypoperfusion of the left ventricle as indicated by a significantly lower 201Tl concentration compared to the baseline state. The most significant decrease in uptake occurred 5 min after injection and was more pronounced in the septal and apical segments. Following intravenous administration of cocaine, instead of gradual disappearance of 201Tl from the left ventricle, there was continuous increase in 201Tl concentration in the left ventricle. These imaging experiments indicate that the deleterious effects of cocaine on the heart are probably due to spasm of the coronaries and decreased myocardial perfusion. Since spasm of the large subpericardial vessels does not seem to explain the magnitude of the increased coronary resistance and decreased coronary flow after cocaine as described in the literature, it is suggested that microvascular spasm of smaller vessels plays a major role in the temporary decrease in perfusion. The data may also suggest that severe temporary myocardial ischemia is probably the initiating factor for the cardiac complications induced by cocaine.

Animals

[Preliminary observation on lymphocyte function with radioisotope incorporation in asthmatic patients].

Twenty-five asthmatic patients and 54 normal subjects were included in this study. The results of our study showed that among the asthmatic group, no obvious decrease was observed in the uptake of 3H-TdR by T-lymphocyte stimulated with PHA, whereas there was markedly depressed uptake of 14C-UR by T-lymphocyte. The latter finding demonstrated that the asthmatic patients had a decrease of RNA synthesis during the course of T-lymphocyte transformation. The mean 3H-TdR uptake by T-lymphocyte was less in the patients whose first attack of asthma occurred after 30 years of age, when compared to those before 30 years of age, but statistically not significant. There was a slightly lower uptake of 3H-TdR by T-lymphocyte in the mild attack group than that in the remission group. B-lymphocyte transformation ability reflected in the uptake of 3H-tyrosine by B-lymphocyte stimulate with LPS was apparently increased in the asthmatic group, as compared to normal subjects. This study supports the hypothesis that the abnormal function of cell-mediated immunity may play a role in the pathogenesis of asthma.

Adolescent