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Biomedical subjects

J Chang

Publications and source records attributed to J Chang.

At least 19 recordsLinked to original sources
PubMed1992

The physical and functional behavior of capture antibodies adsorbed on polystyrene.

Six monoclonal and two polyclonal antibodies to fluorescein (FLU) were affinity purified and immobilized on Immulon 2 polystyrene as capture antibodies (CAbs): (a) by passive adsorption at pH 9.6, (b) via a streptavidin bridge to a biotinylated carrier molecule, and (c) via an antiglobulin which had been previously adsorbed passively to the polystyrene. Data show that less than 3.0% of the binding sites of monoclonal CAbs and approximately 5-10% of those of polyclonal CAbs were capable of capturing antigen (FLU4.2-BSA) after passive adsorption. Immobilization of CAbs via an antiglobulin or a streptavidin bridge, resulted in the preservation of antibody binding sites to greater than 70% for some monoclonals although immobilization via the streptavidin bridge resulted in the highest number of functional sites/well. The data presented are consistent with studies on other adsorbed proteins which demonstrate that passive adsorption on polystyrene results in the loss of protein function. Furthermore, these data show that generally less than half of the binding sites of antibodies available in solution are available after solid-phase immobilization even when non-adsorptive methods are employed. Some polyclonal anti-FLU also have lower average avidity following passive adsorption compared with CAbs immobilization via a streptavidin bridge. Immunochemical studies revealed that adsorbed polyclonal-CAbs performed like monoclonals when tested with multivalent antigens (FLU10-IgA) but in an expected heterogeneous manner in Scatchard plots when tested using univalent FLU-insulin. This observation implied cross-linking of immobilized CAbs by the multivalent antigen. Because only 5-10% of adsorbed polyclonal CAbs are active, the survivors must be non-randomly distributed in clusters to explain the cross-linking. This was confirmed by scanning electron microscopy which gave rise to the hypothesis that antibodies which retain activity after adsorption, are those present in clusters, i.e., the functional adsorbed CAb is an antibody cluster. Data presented in this report on the behavior of adsorbed CAbs, and reviewed from the work of others for various adsorbed proteins, indicate that the method of passive adsorption at pH 9.6, which is widely used in popular microtiter ELISAs, and which has in many ways revolutionized immunoassay, is a method of protein denaturation. Assayists that utilize passive adsorption of proteins on hydrophobic supports as part of their research need to be cognizant of this phenomenon, while inventors of immunoassay should develop alternative methods of immobilization which do not destroy 90% of the functional activity of solid-phase reactant.

Adsorption↗
PubMed1992

Haemopoietic cell kinetics in humans treated with rGM-CSF.

We have investigated the kinetics of myeloid cell proliferation in the marrow of patients with small-cell lung cancer and treated with 10 daily subcutaneous injections of granulocyte/macrophage colony-stimulating factor (GM-CSF). Bone marrow, obtained before and during treatment with the growth factor, was labelled in vitro with tritiated thymidine (3H-TdR). A 3rd bone-marrow sample was obtained 1 hr following an intravenous injection of 3H-TdR. Subsequent daily blood samples were also collected, and 3H-TdR labelling was assessed on these and the marrow preparations by autoradiography. GM-CSF treatment increased the peripheral granulocytic cells nearly 5-fold, but this included significant eosinophilia, so that the neutrophilic granulocytes increased only 3.3-fold. These cells were released from the marrow over a normal time scale, but their peripheral half-life was about 6 times longer than normal and they were probably functionally defective. Furthermore, significant numbers of immature cells were released from the marrow. Neutrophil production stimulated by GM-CSF was thus overestimated by measurement of the apparent peripheral granulocytosis. Increased labelling indices and grain counts in the proliferating granulocytic cells of the marrow indicate shortened cell-cycle times, and the excess granulocyte production appears to be the result of extra amplification divisions in the proliferative compartments.

Carcinoma, Small Cell↗
PubMed1992

Occupation, smoking, and the risk of high-grade invasive bladder cancer in Missouri.

Numerous epidemiological studies have established that occupational exposures and smoking are the two major known risk factors for the development of bladder cancer. Using data from the Missouri Cancer Registry, we investigated the hypothesis that individuals with occupationally-related bladder cancer are more likely to have a more invasive form of the disease. Data were analyzed for 2,893 white males diagnosed with primary bladder cancer in Missouri between 1984 and 1988. Of the 1,415 cases whose occupational status was recorded, 236 (17%) were employed in high-risk occupations. Cases with high-grade disease were more likely to have been employed in a high-risk occupation, after adjustment for age and smoking (adjusted odds ratio [AOR] = 1.7, 95% confidence interval [CI] = 1.1-2.6). High-risk workers under 60 years of age were most at risk for developing high-grade bladder tumors (AOR = 2.3, 95% CI = 1.0-5.3). There was no overall association between high-risk occupation and late-stage disease (AOR = 1.1, 95% CI = 0.7-1.5), but it was present in the men younger than 60 years of age (AOR = 2.0, 95% CI = 1.0-3.8). No association was found between tobacco use and grade (AOR = 1.1, 95% CI = 0.8-1.5), but cases with late-stage disease were more likely to be smokers (AOR = 1.5, 95% CI = 1.1-1.9). When occupations were examined individually, motor vehicle operators, truck drivers, vehicle mechanics, other mechanics, and janitors were among those most likely to be diagnosed with high-grade or late-stage tumors. Although further studies are necessary to confirm these results, they suggest that surveillance and targeted screening of workers in high-risk occupations may result in a greater yield of early invasive cancers and possibly decrease the mortality associated with this disease.

Aged↗
PubMed1992

Chromatographic characterization of CA 19-9 molecules from cystic fibrosis and pancreatic carcinoma.

We have compared the size, the binding to Concanavalin A (Con A), and the affinity for monoclonal antibody 1116NS-199 (Mab 19-9) among CA 19-9 molecules from sera of cystic fibrosis (CF) and pancreatic carcinoma patients and from sputum extracts. CA 19-9 molecules of two different sizes were found in all types of specimens by Sepharose 4B chromatography. While the smaller CA 19-9 molecule was predominant in CF patient sera, the larger molecule was associated with most of the sera from patients with pancreatic carcinoma. The majority of the sputum extracts contained the larger CA 19-9 molecule. All CA 19-9 molecules studied by Con A chromatography did not appear to bind to Con A, and almost 100% were found in the nonreactive fraction. The CA 19-9 molecules from sera of either CF or pancreatic carcinoma patients exhibited variable affinities for Mab 19-9, some approaching that of the standard curve but many also having lower affinities. The lowest affinity was displayed by CA 19-9 molecules from the sputum extract. It appears that development of more specific assays for CF and for carcinoma is possible if the correct CA 19-9 molecule is selected for antibody preparation and for use as standards.

Antibodies, Monoclonal↗
PubMed1992

Characterization and pharmacological modulation of soluble phospholipase A2 generated during glycogen-induced rat peritonitis.

Soluble phospholipase A2 (PLA2) activity was assessed in rat peritoneal lavage fluid after an intraperitoneal injection of 6% glycogen. Enzyme activity immediately increased 5-fold above basal by 4 h. Activity decreased by only 30% at 18 h and remained at this elevated level through 72 h. The initial rise in PLA2 activity was coincident with protein extravasation but not with polymorphonuclear leukocyte infiltration, suggesting that the early PLA2 activity could be, in part, blood-derived. Mononuclear cell influx occurred later (4 h), peaked by 6-8 h but remained elevated through 72 h possibly contributing to the persistence of PLA2 activity through 20-72 h. The exudate PLA2 measured at 4-6 h (early) and 20-24 h (late), after glycogen administration, were biochemically compared. They were found to be neutral pH active, Ca(2+)-dependent and were similarly inhibited by the inhibitors, p-bromophenacylbromide, ellagic acid, gossypol and luffariellolide. Oral administration of dexamethasone to rats inhibited the appearance of PLA2 activity in the peritoneal lavage fluid as well as cellular influx and protein extravasation. Indomethacin had no effect on these parameters. These studies demonstrate that PLA2 is an integral component of glycogen-induced peritonitis and can be pharmacologically manipulated.

Animals↗
PubMed1992

Shear bond strength of a 4-META adhesive system.

This study evaluated the shear bond strength between amalgam and amalgam, amalgam and composite resin, and amalgam and dentin using a 4-META adhesive. Eighty samples were divided into four groups of 20 and were then divided into subgroups of 10 samples for thermocycling procedures. This study indicated that amalgam bonded to amalgam with a 4-META adhesive yielded bond strengths that were weaker than the shear strength of amalgam itself (p less than 0.05), and that thermocycling appeared to significantly weaken bond values (p less than 0.02).

Adhesives↗
PubMed1992

Differential detection of Mycoplasma pulmonis and Mycoplasma arthritidis with species-specific DNA probes.

Mycoplasma pulmonis and Mycoplasma arthritidis are both significant causes of infection in colonies of rodents, which are common experimental animals for biomedical research. Since differential diagnosis has proven difficult due to similar homology between these two murine Mycoplasma species, the development of a reliable identification system is of importance. In this study DNA probes specific for M. pulmonis and M. arthritidis were generated after cross-hybridization between two reference strains and cloning of the specific DNA fragments into the pGEM-3 blue vector. Two clones, harboring plasmids pGEM-89 (specific for M. pulmonis) and pGEM-31 (specific for M. arthritidis) were selected based on their specificity upon colony hybridization and were used as species-specific probes. These probes could detect in dot blots 150 pg of M. pulmonis DNA or 300 pg of M. arthritidis DNA with no visible hybridization with up to 100 ng of heterologous DNA. When hybridized with dot blots of culture grown organisms, the pGEM-89 probe produced a positive signal with all 12 isolates of the M. pulmonis strains tested, but none of the four M. arthritidis, and vice versa for the pGEM-31 probe. We thus anticipate that these probes will be useful for routine detection and identification of mycoplasmal infections of rodents.

Animals↗
PubMed1992

Infection risk in patients with small cell lung cancer receiving intensive chemotherapy and recombinant human granulocyte-macrophage colony-stimulating factor.

The effect of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was assessed in 17 patients with small cell lung cancer. GM-CSF was initially given alone by subcutaneous injection for 10 days at 50-500 micrograms/m2 per day. There was a significant rise in neutrophils and eosinophils and to a lesser extent in monocytes at all dose levels. During the next phase, patients received chemotherapy (etoposide, ifosfamide and doxorubicin), and GM-CSF was given on alternate cycles, the patients acting as their own controls, so that the amelioration of chemotherapy could be assessed. Despite partial abrogation of the neutropenia associated with chemotherapy (P = 0.04), GM-CSF failed to reduce the frequency of febrile episodes in association with neutropenia, with six episodes occurring on GM-CSF and seven while patients were not receiving GM-CSF after a total of 66 cycles of chemotherapy. After GM-CSF, there was a reduction in polymorph phagocytic ability and chemotaxis in 6/12 and 9/11 patients, respectively. Timed blood counts after GM-CSF administration showed that peak leucocytosis occurred at 8-12 h and fell to two-thirds of this level at 24 h. Toxicity consisting of lethargy, myalgia and bone pain occurred at all dose levels but was manageable. 2 patients had thromboembolism. This study failed to demonstrate a reduction in the infection risk associated with moderately intensive chemotherapy for small cell lung cancer despite the partial abrogation of neutropenia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Controllability and duration of stress alter central nervous system depressant-induced sleep time in rats.

Rats were exposed to either 80 escapable shocks or yoked inescapable shocks and then injected with several hypnotic doses of sodium pentobarbital, midazolam, or ethanol; their sleep-time duration was compared with that of naive controls. Inescapable shock exposure resulted in a significant increase in ethanol-induced sleep time compared with the escapable shock and naive control groups. Both escape and yoked groups showed an increase in barbiturate-induced sleep time compared with controls, although no difference was observed for midazolam. Acute stress (twenty 5-s inescapable shocks) did not alter the depressant-induced sleep time for any of the drugs tested. These results illustrate the importance of psychological aspects of stress and its influence on the potency of certain depressants.

Animals↗
PubMed1992

Viability of neocortical function shown in behavioral activation state PET studies in Alzheimer disease.

Twenty subjects with mildly to moderately severe Alzheimer disease (AD) and 14 normal elderly control subjects were studied using [18F]fluorodeoxyglucose and positron emission tomography (PET) to investigate regional cerebral glucose metabolism during both a resting state and a behavioral activation state, utilizing a reading memory task (RMT). The RMT produced significant global metabolic activation of 15 +/- 15% in normal subjects and 11 +/- 13% in AD subjects. The occipital regions were preferentially activated, but all regions in both groups were also significantly activated. The RMT did not allow a better discrimination of AD patients from normal controls on the basis of regional metabolic deficits. Regions in the AD group that were individually classified as hypometabolic during rest also exhibited metabolic activation. The apparent viability of hypometabolic regions in AD patients challenges current hypotheses regarding the cause of abnormal metabolism in AD.

Alzheimer Disease↗
PubMed1992

Medical students' knowledge and misconceptions about aging: responses to Palmore's Facts on Aging Quizzes.

Palmore's Facts on Aging Quizzes I and II and Facts on Aging Mental Health Quiz were administered as a single test to third-year medical students before and after their 6-week Community Health and Family Medicine clerkship. The clerkship experience contributed to a small improvement in students' knowledge about the aged, net bias scores decreased from pre- to posttest, and scores on FAQI were significantly higher than scores on FAQII both pre- and posttest.

Aged↗
PubMed1992

Recombinant interleukin 4 stimulates human immunodeficiency virus production by infected monocytes and macrophages.

Recombinant interleukin 4 (IL-4) stimulated extracellular (EC) and intracellular (IC) production of human immunodeficiency virus (HIV) from infected human blood-derived monocytes and macrophages when incubated with the cells after but not before virus inoculation. Significant stimulation was observed in 20 of 27 experiments with monocytes (inoculated with HIV immediately after adherence) and 10 of 13 experiments with macrophages (inoculated after 5 days adherence) using a total of 30 normal donors of monocytes and macrophages, and 11 recent isolates of monocytotropic HIV strains (after one passage in mononuclear cells). Marked increases in EC and IC HIV antigen were observed in some experiments, which were comparable with the maximal stimulatory effects of other cytokines such as IL-2. IL-4 also had similar effects on infectious HIV concentration as measured by reverse transcriptase and TCID50 assays. Antibody to IL-4 prevented the stimulatory effect of the cytokine. The proportion of monocytes and macrophages infected by HIV, as determined by in situ hybridization, also increased after incubation with IL-4 for 7 days. The most marked effects were observed with HIV-infected macrophages, for which the proportion of unstimulated infected cells was lower (35 to 45% increasing to 66 to 70% with IL-4 treatment). There was also an increased proportion of cells with high granule concentrations, suggesting that IL-4 increases the intracellular concentration of viral nucleic acids. This was supported by semi-quantitative hybridization experiments showing that total HIV RNA increased in IL-4-stimulated monocytes 48 to 96 h after HIV inoculation. A marked increase in aggregates was observed on day 7 in HIV-infected monocytes treated with IL-4, compared to that in HIV-infected cells alone or IL-4-treated uninfected monocytes. These findings suggest that IL-4 stimulates HIV replication in the early phases of infection and may also facilitate virus transmission by aggregate formation.

Base Sequence↗
PubMed1992

Effect of posture on arterial oxygenation in patients with chronic obstructive pulmonary disease.

We studied 117 patients with chronic obstructive pulmonary disease (COPD) to evaluate (1) the frequency and magnitude of postural changes in resting arterial oxygenation and (2) the relationship of these changes to other measures of pulmonary function and exercise arterial blood gases. Compared to the supine measurement, room air PaO2 measured while standing increased more than 3 mm Hg in 28 patients (group 1), did not change (+/- 3 mm Hg) in 57 patients (group 2), and decreased more than 3 mm Hg in 32 patients (group 3) (range = 31 mm Hg increase to 20 mm Hg decrease). Patients in group 1 had significantly less severe disease than patients in the other two groups. There were no significant pulmonary function differences between groups 2 and 3. Supine PaO2 was similar for all groups, suggesting that standing PaO2 accounted for the postural change in PaO2. Because of unpredictable postural changes in PaO2 in patients with COPD, we believe that body position should be noted for arterial blood gas measurements and should be kept constant for valid comparison of serial measurements. These findings may also be important for other diffuse lung diseases.

Arteries↗
PubMed1992

Natural killer activity and antibody-dependent cellular cytotoxicity in patients with primary lung cancer.

The NK activity and ADCC of peripheral blood mononuclear cell were examined to evaluate the contribution of ADCC and NK activity to host immune response against lung cancer. The NK activity and ADCC were examined in 58 patients with primary lung cancer and 40 healthy volunteers as normal controls. The NK activity of patients with lung cancer was significantly subnormal, but ADCC was at a normal level. The NK activity was decreased in non-small cell lung cancer (NSCLC), but not in small cell lung cancer (SCLC) compared to normal controls. According to stage, the NK activity in stage II, III-M0 and III-M1 NSCLC showed low levels compared to that of stage I NSCLC, but there was no difference of NK activity in patients with SCLC. The NK activity was not affected by performance status. There was no significant difference of ADCC in patients with lung cancer according to cell type, stage and performance compared with that of normal controls. The NK activity and ADCC were not changed after chemotherapy and operation respectively.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1992

Detection of Mycobacterium tuberculosis in clinical samples from patients with tuberculosis or other pulmonary diseases by polymerase chain reaction.

Polymerase chain reaction (PCR) using primers targeting the IS6110 repetitive sequence was employed to detect Mycobacterium tuberculosis in 228 samples from patients with tuberculosis or other pulmonary diseases and controls, and the results were compared with culture and clinical findings. None of culture negative samples from 17 healthy controls were PCR positive. Of 109 active tuberculosis patients under chemotherapy, 88 (80.7%) were PCR positive and were significantly higher than 63 (57.8%) positive by culture. Fifty-nine (93.7) of 63 culture positive and 29 (63.0%) of 46 culture negative specimens contained M. tuberculosis detectable by PCR. In 41 specimens from inactive tuberculosis patients who visited to the chest clinic because of chest problems, 16 (39.0%) also gave PCR positive results. In addition, 14 (46.7%) of 30 specimens submitted for M. tuberculosis culture from patients with pulmonary diseases were PCR positive. Presumptive diagnosis of these PCR positive patients was bronchitis, pneumonia, bronchial asthma, etc. Therefore, this study suggests that PCR is sensitive and specific in detecting M. tuberculosis in clinical specimens. However, the interpretation of the PCR results in specimens from patients with pulmonary diseases should be done cautiously in areas with a high prevalence of tuberculosis.

Base Sequence↗
PubMed1992

Drug-induced fatal aplastic anemia following cataract surgery.

Aplastic anemia attributed to medications used in ophthalmology is rare. We report a fatal case that developed in a 73-year-old woman 7 weeks after cataract extraction performed under local anesthesia. Postoperative medications included a chloramphenicol-containing ointment, flurbiprofen sodium drops, prednisone acetate drops and orally given acetazolamide. It was felt that the aplastic anemia was related to therapy with chloramphenicol or acetazolamide or both. We recommend that the course of prophylactic antibacterial therapy after intraocular surgery be kept short, regardless of the preparation used. We urge caution in the choice and use of drugs known to be associated with aplastic anemia and recommend close monitoring of the hemogram.

Acetazolamide↗
PubMed1992

Management of ophthalmic complications of facial nerve palsy.

Six stages--supportive care (with or without tarsorrhaphy), planning for facial reanimation, lower eyelid and lateral canthal resuspension, passive upper eyelid reanimation, dynamic eyelid reanimation, and soft tissue repositioning--should be considered in the management of the ophthalmic complications of facial nerve palsies. Each stage should be considered in order, although action in each stage may not be appropriate for all patients. In addition, after appropriate consideration, two or more staged procedures may be performed at the same time. Treatment may be held at any stage in which the cornea is compensated and the patient is comfortable and happy. By employing this staged approach, the surgeon has a method of organizing therapy in a logical fashion, and the patient is offered a set of reassuring goals, which combine to make the treatment plan more effective.

Eyelid Diseases↗