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Biomedical subjects

J S Wang

Publications and source records attributed to J S Wang.

At least 19 recordsLinked to original sources

Outbreak of bronchiolitis obliterans associated with consumption of Sauropus androgynus in Taiwan.

BACKGROUND: In August, 1995, there was an outbreak in Taiwan of rapidly progressive respiratory distress associated with consumption of uncooked Sauropus androgynus, a vegetable with a claimed yet unconfirmed effect on weight control. We report on 23 patients with strikingly similar clinical presentations. METHODS: A structured questionnaire for clinical manifestations was completed. Radiographic findings, pulmonary physiological changes, immunological and microbiological studies, and pathological examination were evaluated. FINDINGS: All patients were young and middle-aged women (mean age 39 years [range 21-52]). They took uncooked S androgynus juice, generally mixed with guava or pineapple juice, for a mean duration of 10 weeks. Progressive dyspnoea and persistent cough were the main symptoms on presentation. Pulmonary function testing uniformly revealed moderate to severe airflow obstruction with mean forced expiratory volume in 1 s (FEV1) of 0.66 L (26% of predicted). No bronchodilator response was observed. Room-air arterial blood gas analysis showed hypoxaemia (mean PaO2 9.6 [SD 1.6] kPa). Chest radiographs were essentially normal. High-resolution computed tomography showed bilateral bronchiectasis and patchy low attenuation of lung parenchyma with mosaic perfusion. Ventilation-perfusion scintigraphic findings were compatible with obstructive lung disease. Histopathology of open lung biopsy specimens in four patients confirmed the presence of bronchiolitis obliterans. Immunohistochemical stains of the open lung biopsy specimens showed predominance of T cells over B cells. Immunofluorescent stains for IgG, IgM, IgA, C1q, C3, and C4 were negative. Serum concentrations of tumour necrosis factor alpha were higher than those of normal controls. Clinical response to prednisolone was limited. INTERPRETATION: We describe an unusual association between bronchiolitis obliterans and ingestion of the vegetable S androgynus. T-cell mediated immunity may be involved in the pathogenesis.

Adult

Is there any difference between vacuum mixing systems in reducing bone cement porosity?

Six vacuum mixing systems, Cemvac, Merck, Mitvac, Optivac, Osteobond, and Stryker, were tested using prechilled Palacos R bone cement to investigate the reduction of porosity compared to mixing at atmospheric pressure. In addition the Optivac, Osteobond, and Stryker were tested using Simplex P bone cement to find out if they were effective in reducing the porosity of a middle viscosity bone cement. All vacuum mixing systems reduced the number of macropores (> 1 mm) and micropores (0.1 mm < voids < 1 mm) and increased the density of both Palacos R and Simplex P. But only the Optivac, Stryker, and Merck systems reduced the area percentage of macropores with more than 50% compared to the control. When using Simplex P bone cement, all three mixing systems tested reduced the numbers and the area percentage of macropores compared to the control. The results show that vacuum mixing is effective in reducing the porosity in both a high viscosity cement such as Palacos R and a middle viscosity cement such as Simplex P. Not all systems tested were effective in reducing the number and size of large voids.

Absorptiometry, Photon

Basic fibroblast growth factor enhances bone-graft incorporation: dose and time dependence in rats.

In a previous study, we found that basic fibroblast growth factor could stimulate bone-graft incorporation. In the present study, the effects of different doses and implantation times were further studied, using the bone conduction chamber, in rats. Inside the chamber, the graft is isolated from the surrounding tissues except at one end, where small openings embedded in host bone allow ingrowth of tissue. The distance that new tissues had reached from the openings into the graft was measured on histological slides. Bone grafts were obtained from the proximal tibiae of donor rats, frozen at -70 degrees C, and lipid-extracted. Before implantation, they were soaked overnight in a hyaluronate gel with or without basic fibroblast growth factor and then were fitted into the chambers, which were implanted in the proximal tibiae of recipient rats. In a dose-response experiment, grafts containing 0.3, 8, 40, 200, or 1,000 ng of basic fibroblast growth factor were compared with grafts treated with carrier gel only, after an implantation time of 6 weeks. Fibrous tissue always penetrated the grafts further than the ingrown bone; the distance that it reached from the ingrowth openings (total ingrowth distance) was increased by all of the doses except 0.3 ng per implant. The distance of bone ingrowth was increased by 8, 40, and 200 ng. The increased total ingrowth with 1,000 ng was due to an increased amount of fibrous tissue ahead of the bone, whereas with the lower doses the increase was due to more bone. Thus, the dose had an effect on the type of ingrown tissue found in the graft. In a time-effect study, grafts treated with 40 ng of basic fibroblast growth factor had a higher uptake of [99mTc]MDP at 2 and 4 weeks and an increased bone ingrowth distance at 10 weeks. The radioactivity from [125I]basic fibroblast growth factor declined with a half-life of 17 hours. The results suggest that basic fibroblast growth factor may be beneficial for the incorporation of contained bone grafts; studies using more clinically relevant models are required.

Animals

Bacterial and human cell mutagenicity and mouse lung tumorigenicity of the oxygenated polynuclear aromatic hydrocarbon phenalenone.

Phenalenone (perinaphthenone) is a major oxygenated polynuclear aromatic hydrocarbon (oxy-PAH) atmospheric pollutant formed from the combustion of fossil fuels. Mutagenicity of phenalenone was measured in quantitative forward mutation assays with Salmonella typhimurium TM677 and metabolically competent human B-lymphoblastoid cell lines (MCL-5 and h1A1v2 cells), and its tumorigenicity was also assessed in a newborn mouse assay. Phenalenone was mutagenic in Salmonella in the presence of rat liver postmitochondrial supernatant (PMS) at a minimum detectable mutagen concentration (MDMC) of 12 micrograms/ml, but was not mutagenic in the absence of PMS at concentrations up to 100 micrograms/ ml. Phenalenone was not significantly mutagenic in either human cell line after 28 hr treatment, although mutant fractions were increased by nearly fivefold in h1A1v2 cells (at the tk locus) exposed at 30 micrograms/ml. However, after 72 hr treatment, phenalenone was mutagenic at the hprt locus in h1A1v2 cells with an MDMC of 3 micrograms/ml. Phenalenone was also tumorigenic in male BLU:Ha mice with a lung tumor incidence of 33% 6 months after injection with 4.2 mg phenalenone, the highest dose tested. Lung tumor multiplicity in this treatment group was 0.5 tumor/mouse. No increase in lung tumors in female mice was observed. Indices of lung tumor incidence (ED50) and multiplicity (TM1.0) for male mice were 29.3 and 34.9 mumol, respectively. These data suggest that phenalenone does not contribute significantly to the mutagenicity or carcinogenicity of combustion emission extracts.

Animals

Percutaneous absorption and tissue distribution of [3H]diacetoxyscirpenol (anguidine) in rats and mice.

Acute toxicity, absorption, excretion, and tissue distribution of topically administered diacetoxyscirpenol (DAS, anguidine) were studied in Fischer rats and CD-1 mice. Mortality (75%) was observed in rats treated with a single dose of 2.625 mg of DAS to 1.44 cm2 of skin, whereas the proportionate (0.75 mg to 0.42 cm2 of skin) and even higher doses were not lethal to mice. Histopathological lesions induced in the rat were similar to those observed by administration through other routes, mainly involving lymphohematopoietic tissues and the gastrointestinal tract. Although lesions in internal organs were less severe, the skin of the mouse was more severely damaged at the application site than that of the rat. During the 90-min period after topical application of a single dose of [3H]DAS, the rat absorbed and retained more [3H]DAS and excreted less radioactivity through urine and feces than the mouse. By 24 hr after treatment, the rat had absorbed, excreted, and retained about twice as much [3H]DAS as had the mouse (p < 0.05 or < 0.005). At 7 days posttreatment, the rat had absorbed more than four times the amount of [3H]DAS than had the mouse (13.1 vs 57.5%; p < 0.005). However, tissues of the mouse retained a higher proportion of administered radioactivity (4.1%) than those of the rat (1.0%; p < 0.05). Total excretion of radiolabel by the rat was approximately sixfold higher than that of the mouse (56 to 9%; p < 0.005). The ratio of excretion in urine to that in feces in the rat was about 2 to 1 (37 to 18%) and in the mouse was about 3.5 to 1 (7 to 2%). Significant differences in the time course of tissue distribution of [3H]DAS in the rat and mouse were found when data were expressed as the percentage of absorbed dose present in tissues or as specific radioactivity (dpm) per gram tissue. These results demonstrated a significant interspecies difference in acute percutaneous toxicity of DAS and different patterns of absorption, excretion, and tissue distribution of topically administered [3H]DAS in rats and mice.

Absorption

Transforming growth factor beta and bone morphogenetic protein 2 for bone ingrowth: a comparison using bone chambers in rats.

We compared the ability of transforming growth factor beta 1 (TGF beta 1) and bone morphogenetic protein 2 (BMP-2) to increase the penetration distances for fibrous tissue and bone into porous coralline hydroxyapatite. Forty-four rats received pairs of titanium bone chambers implanted bilaterally in their proximal tibiae. These chambers allow tissue ingrowth from one end of a long cylinder, so that ingrowth distances along the cylinder axis can be measured. Since bone never grows as far as fibrous or undifferentiated mesenchymal tissue, we measured both total tissue ingrowth and bone ingrowth distances. All chambers were implanted with cylinders of porous hydroxyapatite (Interpore 200). The hydroxyapatite cylinders were treated with either 1, 33, or 1000 ng of TGF beta 1 or BMP-2 prior to implantation, and compared with untreated contralateral control implants at 6 weeks. The bone ingrowth distance into the porous hydroxyapatite showed a trend toward inhibition with TGF beta 1 as compared to untreated controls (p < 0.08), and there was a negative correlation between TGF beta 1 dose and ingrowth distances for both bone (p < 0.01) and total tissue (p < 0.01). BMP-2 greatly increased bone (p < 0.001) and total tissue (p < 0.001) ingrowth distances.

Animals

An aflatoxin-associated mutational hotspot at codon 249 in the p53 tumor suppressor gene occurs in hepatocellular carcinomas from Mexico.

The p53 tumor suppressor gene is commonly mutated in human hepatocellular carcinoma (HCC). The most frequent mutation in HCC in populations exposed to a high dietary intake of aflatoxin B1 (AFB1) is an AGGarg-->AGTser missense mutation in codon 249 of the p53 gene. We analyzed HCCs from Monterrey, Mexico, for the codon 249ser hotspot mutation. We also analyzed the serum AFB1-albumin adduct levels of the donors and family members to measure the current AFB1 exposure in this population. Moreover, the presence of hepatitis B and/or C viral infection (HBV or HCV) was analyzed serologically in the patients. Tumor cells were microdissected from tissue sections and exon 7 p53 sequences were amplified by polymerase chain reaction from genomic DNA and sequenced directly. The serological tests for anti-p53 antibodies, HBV or HCV were done by ELISA. Immunohistochemical analysis of p53 protein was done using a polyclonal rabbit antiserum (CM-1). Eight of 21 cases were positive by p53 immunohistochemistry. Of the 16 cases sequenced for exon 7 of p53 three codon 249 AGGarg-->AGTser mutations were found. Serum antibodies recognizing p53 protein were found in one of 18 patients. Positive serology for HBV and/or HCV was found in 12 of 20 cases. The serum AFB1-albumin adduct levels in this population ranged from 0.54 to 4.64 pmol aflatoxin/mg albumin. These results indicate that dietary AFB1 and hepatitis viruses are etiological agents in the molecular pathogenesis of HCC in this geographic region of Mexico.

Adult

Flow-induced detachment of adherent platelets from fibrinogen-coated surface.

A study of the shear forces under which adherent platelets of different morphologies can be detached from surfaces was carried out using a newly designed tapered flow chamber, which covered the entire shear range of physiological circulation. Platelets that naturally settled on a fibrinogen-coated surface were exposed to shear flow and were subsequently processed for scanning electron microscopic observation. We found that 1) the density of platelets remaining after flow exposure decreased with local shear stress, 2) adherent platelets of different morphologies withstood different levels of shear stress: most round cells and 40% of the cells that had a few short pseudopods were detached at < 10 dyn/cm2, whereas most spread cells could withstand 50 dyn/cm2, 3) pulsatile flow was more effective in removing adherent platelets than equivalent steady flow, 4) cytochalasin D and colchicine retarded platelet shape change and made them more easily detached by shear forces, and 5) metabolic energy-depleted platelets spread readily and formed shear-resistant clumps. Our observations indicated that adherent platelets of different morphologies on a fibrinogen-coated surface could withstand different levels of flow shear stress.

Blood Circulation

Sensory nerve ingrowth during bone graft incorporation in the rat.

We studied nerve ingrowth into a cancellous bone graft in a bone conduction chamber model in the rat. Before implantation of the chamber bilaterally in the proximal tibiae of 8 Sprague-Dawley rats, a defatted cancellous bone graft from separate donor rats was fitted snugly into each chamber. After 6 weeks, the animals were perfused with Zamboni's fixative and the chambers were harvested. Immunohistochemical detection of nerve fibers was performed in cryostat sections, using antisera to protein gene product 9.5 (PGP 9.5), neural growth-associated protein GAP-43/B-50, calcitonin gene-related peptide (CGRP), substance P and C- flanking peptide of neuropeptide Y (CPON). Nerve fibers were found in 10 out of 16 samples in the newly formed bone, and also in the fibrous tissue which had penetrated deeper into the graft. The nerve fibers were mainly of sensory origin, as they showed immunoreactivity for CGRP and GAP-43/B-50. We speculate that the nerve fibers may act as transmitters of nociceptive impulses from the graft, and as transport pathways for neuropeptides that are actively involved in angiogenesis and in the recruitment and activity of osteogenic cell populations from the graft recipient.

Animals

Basic fibroblast growth factor infused at different times during bone graft incorporation. Titanium chamber study in rats.

We investigated the effect of applying basic fibroblast growth factor (bFGF) to a bone graft during different stages of incorporation in an infusion bone chamber model. Bone chambers were implanted bilaterally into rat tibiae. Both chambers were connected to an implanted osmotic minipump. Ingrowing bone could enter the cylindrical interior of the chamber only at one end. The distance which ingrowing bone had reached into the bone graft was then measured on histological slides. Specimens were also analyzed by 99mTc-MDP scintimetry. The infusion of buffer during 2 weeks from implantation had no effects on tissue ingrowth distance or quality. bFGF was infused during 2 weeks from implantation in a dose of either 1.2 or 12 ng/day. Bone ingrowth was measured 6 weeks after implantation. The higher dose had a more marked effect and was used for studying the effect of application at different times. The maximum stimulation of bFGF as measured at 6 weeks postimplantation was found after infusion during the first postimplantation week. Infusion during the third and fourth weeks had no effect at 6 weeks, but tended to increase the bone ingrowth distance at 8 weeks postimplantation. These findings suggest that bFGF infusion increases bone ingrowth into bone grafts when infused at both an early and a later stage, but the effect can be measured only several weeks later.

Animals

Basic fibroblast growth factor for stimulation of bone formation in osteoinductive or conductive implants.

Basic Fibroblast Growth Factor (bFGF) is one of the endogenous factors found in bone matrix. bFGF is a mitogen for many cell types, including osteoblasts and chondrocytes. It can stimulate angiogenesis and osteoblast gene expression. The purpose of this study was to investigate whether exogenous bFGF can stimulate the formation of bone in bone grafts and in a bone graft substitute. In a model using demineralized bone matrix implants for bone induction, a dose of 15 ng bFGF per implant increased the number of chondrocytes and the amount of bone, whereas 1900 ng greatly inhibited cartilage and bone formation. These results are consistent with previous studies with this model, showing that a lower dose of bFGF increased bone calcium content and a higher dose reduced it. Thus, exogenous bFGF can stimulate proliferation during early phases of bone induction. A new device, the bone conduction chamber, was developed for the application of bFGF to bone conductive materials. This model made it possible to demonstrate a difference between the conductive properties of bone grafts and porous hydroxyapatite. bFGF increased bone ingrowth into bone graft inside the chamber and showed a biphasic dose-response curve, so that 8-200 ng per implant (0.4-10 ng/mm3) increased bone ingrowth, but higher or lower doses had no effect. The same doses had the same effects in porous hydroxyapatite. In both bone grafts and porous hydroxyapatite, the highest dose still caused an increase in ingrowth of fibrous tissue. The effect on bone ingrowth was first detected after 6 weeks, regardless if administration of bFGF started at implantation or 2 weeks later, using an implanted minipump. Hyaluronate gel was effective as a slow-release carrier for bFGF. In conclusion, bFGF stimulates bone formation in bone implants, depending on dose and method for administration.

Animals

Influence of callus deformation time. Bone chamber study in rabbits.

Short periods of strain have effects on tissue differentiation in a skeletal defect. Little is known about the importance of the duration of such periods. The authors compared 2 short daily periods of strain pulses that differed only by their duration. This was done by using the micromotion chamber, which is a titanium implant with a transverse intraosseous canal. Fibrous tissue forms in the canal and then is replaced by bone through membranous (metaplastic) ossification. The tissue in the canal can be exposed to cyclic deformation. The chamber allows harvest of the tissue within the canal without disturbing the outer parts of the implant or the surrounding bone, thus enabling repeated experiments in the same animal. Chambers were inserted in 6 rabbits and repeatedly harvested at 3-week intervals. Between harvests, the chambers were subjected to either no motion, 20 cycles once daily during 20 seconds (1 Hz), or 20 cycles once daily during 120 seconds (0.17 Hz). Altogether 39 harvested specimens were studied. The 20-second treatment tended to increase the amount of ingrown bone as compared with no motion, whereas the 120-second treatment caused a marked decrease in bone formation and increase in fibrous tissue. Because the acute tissue trauma appears similar with both deformation treatments, it would appear that the increased fibrous tissue formation with the longer deformation time is caused by the parameters of tissue deformation and not by increased tissue damage.

Analysis of Variance

Human papillomavirus in cyclophosphamide and diverticulum-associated squamous cell carcinoma of urinary bladder: a case report.

The association of cyclophosphamide therapy with the development of urothelial malignancy has been documented. Bladder diverticula associated with squamous cell carcinoma were also identified. In addition, incorporation of human papillomavirus (HPV) deoxyribonucleic acid (DNA) has been previously shown in urothelial carcinoma by in situ hybridization technique. Here a case is reported of bladder squamous cell carcinoma occurring four years after intravenous pulse therapy with cyclophosphamide in a patient with bladder diverticula where HPV was identified in the lesion. To present knowledge, this is the first case report of bladder squamous cell carcinoma with simultaneous occurrence of three risk factors for urothelial malignancy: cyclophosphamide therapy, diverticulum, and HPV infection.

Adult

Temporal patterns of aflatoxin-albumin adducts in hepatitis B surface antigen-positive and antigen-negative residents of Daxin, Qidong County, People's Republic of China.

Molecular epidemiological studies of populations at high risk for liver cancer have shown that hepatitis B virus (HBV) and aflatoxin B1 (AFB1) exposure are two major risk factors for this disease. These etiological agents, combined with nutritional deficiencies, are important for the initiation and promotion of liver cancer in various parts of the world. In Qidong, People's Republic of China, liver cancer accounts for 10% of all adult deaths, and both HBV and AFB1 exposures are common. To study temporal and possible chemical-viral interactions in people, serum samples were collected during a longitudinal study designed to measure aflatoxin molecular biomarkers in residents of Daxin Township, Qidong City, People's Republic of China. In this study, the temporal modulation of aflatoxin adduct formation with albumin over multiple lifetimes of serum albumin was examined in both HBV-positive and HBV-negative people in two periods: September-December 1993 (wave 1) and June-September 1994 (wave 2). During the 12-week monitoring period of wave 1, 120 individuals (balanced by gender and HBV status) provided a total of 792 blood samples. AFB1-albumin adducts were detected in all but one of the serum samples. The range of binding detected by RIA in the Daxin population was 0.17-4.39 pmol AFB11/mg albumin with an overall mean +/- SD of 1.51 +/- 0.21 pmol AFB11/mg albumin. The mean +/- SD for weeks 0, 2, 4, 6, 8, 10 and 12 of wave 1 were 1.21 +/- 0.41, 1.58 +/- 0.70, 1.36 +/- 0.52, 1.71 +/- 0.44, 1.18 +/- 0.60, 2.00 +/- 0.59, and 1.68 +/- 0.34 pmol AFB1/mg albumin, respectively. During wave 2, 103 individuals from wave 1 provided a total of 396 blood samples collected monthly over wave 2, with mean +/- SD aflatoxin-albumin adduct levels of 1.19 +/- 0.37, 0.85 +/- 0.45, 0.89 +/- 0.28, and 0.61 +/- 0.15 pmol AFB1/mg albumin. Using linear regression models, the mean aflatoxin-albumin adduct levels increased (P < 0.05) during the 12 weeks of wave 1 and decreased (P < 0.05) over the 4 months of wave 2. Neither HBV surface antigen status nor gender modified either the baseline mean or the temporal trend. High-performance liquid chromatography confirmation was done on a subset of serum samples, and the results show an excellent association between the immunoassay data and high-performance liquid chromatography. Taken together, these data demonstrate that AFB1-albumin is a sensitive and specific biomarker for assessing exposure to this carcinogen in the population in Qidong.

Adult

Molecular biomarkers for aflatoxins: from adducts to gene mutations to human liver cancer.

Over the past 30 years there have been extensive efforts to investigate the association between aflatoxin exposure and human liver cancer. These studies have been hindered by the lack of adequate dosimetry data on aflatoxin intake, excretion, and metabolism in people, as well as by the general poor quality of worldwide cancer morbidity and mortality statistics. These realities have spurred the efforts to develop new technologies to assess exposure status and risk for aflatoxins, and these agents are among the few environmental carcinogens for which quantitative risk assessments have been attempted. One of the goals of these risk assessments has been the development of primary and secondary preventive intervention methods to lower the human health impact from aflatoxin exposures. The long-term goal of the research described herein is the application of biomarkers to the development of preventive interventions for use in human populations at high risk for cancer. Several of the aflatoxin-specific biomarkers have been validated in epidemiologic studies and are now available for use as intermediate biomarkers in prevention trials. The development of these aflatoxin biomarkers has been based upon the knowledge of the biochemistry and toxicology of aflatoxins gleaned from both experimental and human studies. These biomarkers have been utilized subsequently in experimental models to provide data on the modulation of the markers under different situations of disease risk. This systematic approach provides encouragement for preventive interventions and should serve as a template for the development for the development and validation of other chemical-specific biomarkers and their application to cancer or other chronic diseases.

Aflatoxins