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Biomedical subjects

L L Chen

Publications and source records attributed to L L Chen.

At least 55 records · Page 3Linked to original sources

[The method of getting the prime diagnostic factors of anterior crossbite in early permanent dentition]

OBJECTIVE:We want to select the prime diagnostic factors of anterior corssibe which cna be used to identify the dental and skeletal anterior crossbite. METHODS: From 85 anterior crossbite patients in early permanent dentistion with accurate diagnosis we selected 70 cases to get the prime diagnostic factors by using stepwise discriminant analysis. They were checked by the other 15 cases, We could assess the effects of the factors by calculating their contribution rates. RESULTS: We get six factors: CoGn,AOBO,S'-Ptm',ANB,MPPP,Ramus Angle. CONCLUSION: They include the most information we need to indentify the dental or skeletal anterior crossbite.

Journal Article↗

Comparative pharmacokinetic and pharmacodynamic studies of human insulin and analogues in chronic diabetic Yucatan minipigs.

Pharmacokinetics and pharmacodynamics of insulin analogues were compared with human insulin in streptozotocin-induced chronic diabetic Yucatan minipigs. After overnight fasting, insulin or one of the insulin analogues (0.6 nmol/kg) in acid solutions (pH approximately 3.0) was administered to the minipigs s.c. The plasma insulin concentrations were then measured by radioimmunoassay at predetermined time intervals although blood glucose levels were monitored continuously. The mean (+/-S.E.) values of DeltaCmax (difference between peak and basal plasma insulin levels) were 598 (+/-21), 528 (+/-44), 176 (+/-21), 325 (+/-60) and 228 (+/-33) pM, respectively, for analogue AspB9GluB27, AspB9, GluB27, AspB28 and insulin. The differences in DeltaCmax values were statistically significant between AspB9GluB27 and insulin (P < .02), and between AspB9 and insulin (P < .01), but not between GluB27 or AspB28 and insulin. Moreover, the mean (+/-S.E.) values of DeltaAUC0-->6 (integrated area between plasma insulin concentration curve and basal level) were 1877 (+/-169), 1897 (+/-70), 485 (+/-36), 500 (+/-32) and 677 (+/-105) pM x hr, respectively, for AspB9GluB27, AspB9, GluB27, AspB28 and insulin. The differences in DeltaAUC0-->6 values were statistically significant between AspB9GluB27 and insulin (P < .05) and between AspB9 and insulin (P < .02), but not between GluB27 or AspB28 and insulin. However, there was no significant difference in the values of Deltanadir (difference between nadir and basal levels) and ABGC0-->12 (integrated area between blood glucose response curve and basal level) between insulin and various analogues. In conclusion, although the insulin analogues are different from human insulin in pharmacokinetics, they exhibit similar biological activity to human insulin in the streptozotocin-induced chronic diabetic minipigs.

Animals↗

Superoxide-dependent peroxidase activity of H48Q: a superoxide dismutase variant associated with familial amyotrophic lateral sclerosis.

Approximately 20% of cases of familial amyotrophic lateral sclerosis are caused by dominant mutations in the Cu,Zn superoxide dismutase. One such mutant, in which histidine #48 has been replaced by glutamine (H48Q), exhibits a novel activity. It can react sequentially with O2- and H2O2 to generate a potent oxidant at its active site, possibly Cu(II)-OH, which then can oxidize urate to the corresponding radical. This O2- -dependent peroxidase activity exerted on a substrate peculiar to motor neurons may be the toxic gain of function which leads to the deleterious consequences of this mutation. G93A, G93R, and E100G were also examined and found not to exert this O2- -dependent peroxidase activity.

Amyotrophic Lateral Sclerosis↗

Delivery of recombinant tetanus-superoxide dismutase proteins to central nervous system neurons by retrograde axonal transport.

The nontoxic C fragment of tetanus toxin (TC) can transport other proteins from the circulation to central nervous system (CNS) motor neurons. Increased levels of CuZn superoxide dismutase (SOD) are protective in experimental models of stroke and Parkinson's disease, whereas mutations in SOD can cause motor neuron disease. We have linked TC to SOD and purified the active recombinant proteins in both the TC-SOD and SOD-TC orientations. Light microscopic immunohistochemistry and quantitative enzyme-linked immunosorbant assays (ELISA) of mouse brainstem, after intramuscular injection, demonstrate that the fusion proteins undergo retrograde axonal transport and transsynaptic transfer as efficiently as TC alone.

Animals↗

Human stomach alcohol and aldehyde dehydrogenases: comparison of expression pattern and activities in alimentary tract.

BACKGROUND & AIMS: Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes responsible for ethanol metabolism in humans. The human stomach has been documented to be involved in the metabolism of first-passed alcohol. The aim of this study was to determine ethanol-metabolizing activities in the stomach with regard to sex, age, enzyme pattern, and polymorphism. METHODS: A total of 209 surgical gastric mucosal specimens were investigated. The expression patterns of ADH and ALDH were identified by isoelectric focusing, and the activities were assayed spectrophotometrically. RESULTS: At 33 or 500 mmol/L ethanol, pH 7.5, the activities in the ADH3 1-1 phenotypic and mu-ADH-expressing mucosal specimens were significantly greater than that in the ADH3 1-2 phenotypic and mu-ADH absent mucosal specimens, respectively. The activities of the ALDH2-inactive phenotypes were significantly lower than that of the ALDH2-active phenotypes at 200 micromol/L acetaldehyde. The gastric ADH and ALDH activities were not significantly different between men and women with respect to age and genetic polymorphism. CONCLUSIONS: The stomach may contribute only a small portion of the alcohol metabolism observed in humans, and the liver may be the major site for first-pass metabolism. Differential expression patterns of ADH and ALDH in the alimentary tract suggest that different vulnerabilities to ethanol-induced mucosal injury may exist.

Adult↗

Conditional oculomotor learning: population vectors in the supplementary eye field.

We have shown previously that the activity levels and preferred directions of supplementary eye field neurons change as monkeys learn to associate nonspatial visual information with a saccade (or the spatial target of that saccade). The present report describes changes in neuronal population vectors (PV) during such learning. PVs based on neuronal activity shortly before and after saccades predicted movement direction poorly in the earliest stage of learning, but as monkeys mastered novel stimulus-response mappings, PV accuracy and magnitude increased significantly.

Analysis of Variance↗

Effects of ozone on normal and potentially sensitive human subjects. Part I: Airway inflammation and responsiveness to ozone in normal and asthmatic subjects.

We report here the results of a multiphase project to assess the significance of airway responsiveness and airway injury in ozone (O3)* sensitivity. In Phase I, we measured the preexposure methacholine responsiveness of 66 normal subjects and then exposed these subjects to 0.2 ppm O3 for 4 hours with moderate exercise. Preexposure methacholine responsiveness was weakly correlated with O3-induced increases in specific airway resistance (sRaw) but not O3-induced declines in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC). In addition, O3-induced lower respiratory symptoms were not well correlated with O3-induced changes in lung function. In Phase II, we exposed 23 normal subjects to O3, following an identical protocol to that of Phase I, and then performed bronchoscopy with proximal airway lavage (PAL), bronchoalveolar lavage (BAL), and bronchial biopsy at 18 hours after exposure. Ozone-induced increases in percentage of neutrophils and total protein concentration were observed in both bronchial fraction and BAL fluids; increased percentage of neutrophils also was observed in PAL fluid. These increases were correlated with O3-induced increases in sRaw, but not with O3-induced declines in FEV1 or FVC. Ozone also appeared to increase expression of intercellular adhesion molecule-1, an important mediator of neutrophil recruitment, in bronchial mucosa. In Phase III, we exposed a group of 19 asthmatic subjects to O3, following a protocol identical to that of Phase II. We then compared the lower respiratory symptom and lung function responses of the asthmatic subjects to those of the 81 normal subjects who participated in Phase I, Phase II, or both. The changes in the PAL and BAL fluids of the asthmatic subjects were compared with those of the normal subjects who participated in Phase II. Although both the asthmatic and nonasthmatic subjects showed significant O3-induced changes in lower respiratory symptoms, FEV1, FVC, and sRaw, no significant differences were found between the groups. For sRaw, however, a nonsignificant trend toward a greater O3-induced increase was noted for the asthmatic subjects. In contrast, the O3-induced increases in percentage of neutrophils and total protein concentration in BAL fluid were significantly greater for the asthmatic subjects than for the nonasthmatic subjects. These data suggest that although the lower respiratory symptom and lung function responses to O3 are not markedly greater in asthmatic subjects than in healthy subjects, the inflammatory response of the asthmatic lung may be more intense.

Adolescent↗

Evolution of directional preferences in the supplementary eye field during acquisition of conditional oculomotor associations.

We assessed the preferred directions (PDs) of supplementary eye field (SEF) neurons during conditional visuomotor learning. Monkeys learned to select one of four saccadic eye movements in response to a foveal instruction stimulus (IS). ISs were either familiar or novel. Each familiar IS reliably evoked one saccade: 7 degrees left, right, up, or down form the central fixation point. Novel ISs initially triggered virtually random responses among those four possibilities, but the monkeys ultimately learned to select the instructed saccade. As reported previously, activity rates on novel IS trials significantly changed during learning. Some of these cells (learning-dependent) also have significant modulation on familiar IS trials, but others (learning-selective) lack such activity. Of the former, the familiar IS activity can be either directionally selective or omnidirectional. For most neurons, PDs were apparent during all phases of learning, but they were rarely constant. Only infrequently did a neuron's PD for novel ISs closely match that for familiar ISs throughout the learning process. In directional learning-dependent cells, the PD usually reoriented near the end of learning to resemble that for familiar IS trials. In omnidirectional cells, initially evident PDs dissipated with learning, even as the cell became more strongly modulated. Learning-selective cells typically began with significant PDs, but became unmodulated as learning progressed. Our findings show a pervasive lability in SEF PDs that may reflect a flexible and rapid remapping between inputs and responses within the premotor cortical network.

Animals↗

Ozone-induced decrements in FEV1 and FVC do not correlate with measures of inflammation.

In order to test the hypothesis that changes in lung function induced by ozone (O3) are correlated with cellular and biochemical indices of respiratory tract injury/inflammation, we exposed 20 healthy subjects, on separate days, to O3 (0.2 ppm) and filtered air for 4 h during exercise. Symptom questionnaires were administered before and after exposure, and pulmonary function tests (FEV1, FVC, and SRaw) were performed before, during, and immediately after each exposure. Fiberoptic bronchoscopy, with isolated left main bronchus proximal airway lavage (PAL) and bronchoalveolar lavage (BAL; bronchial fraction, the first 10 ml of fluid recovered) of the right middle lobe, was performed 18 h after each exposure. The PAL, bronchial fraction, and BAL fluids were analyzed for the following end points: total and differential cell counts, and total protein, fibronectin, interleukin-8 (IL-8), and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations. The study population was divided into two groups, least-sensitive (n = 12; mean O3-induced change in FEV1 = -7.0%) and most-sensitive (n = 8; mean O3-induced change in FEV1 = -36.0%). We found a significant O3 effect on SRaw (p<0.001) and lower respiratory symptoms (p<0.001) for all subjects combined, but no significant differences between the least- and most-sensitive groups. Ozone exposure increased significantly percent neutrophils in PAL (p=0.01); percent neutrophils, total protein, and IL-8 in bronchial fraction (p<0.001, p<0.001, and p<0.01, respectively); and percent neutrophils, total protein, fibronectin, and GM-CSF in BAL (p<0.001, p<0.001, p<0.01, p=0.05, respectively) for all subjects combined; there were no significant differences, however, between least- and most-sensitive groups. Our results indicate that levels of O3-induced symptoms and respiratory tract injury/inflammation were not correlated with the magnitude of decrements in FEV1 and FVC.

Adult↗

Pulmonary complications of HIV infection in Dar es Salaam, Tanzania. Role of bronchoscopy and bronchoalveolar lavage.

To determine the pulmonary complications in HIV-1-infected patients in Dar es Salaam, Tanzania, and to evaluate the diagnostic utility of bronchoscopy and bronchoalveolar lavage, we carried out a prospective study of 237 patients with acute respiratory disease who were hospitalized at Muhimbili Medical Center (MMC). Diagnoses were made using well-defined criteria. Of the total, 127 (54%) were HIV-1-seropositive and 110 (46%) were seronegative. Tuberculosis was the most common diagnosis occurring in 95 (75%) HIV-1-seropositive and 87 (79%) seronegative patients. Bacterial pneumonia was the next most common diagnosis occurring in 18 (14%) HIV-1-seropositive and 17 (15%) seronegative patients. Pneumocystis carinii pneumonia was diagnosed in one and Kaposi's sarcoma was seen in only two HIV-1-seropositive patients. Bronchoscopy with bronchoalveolar lavage was the sole source of a diagnosis in nine (8%) seropositive and six (5%) seronegative patients. We conclude that the HIV seroprevalence rate among patients hospitalized for acute respiratory disease at MMC is extremely high. Tuberculosis was the most common cause of pulmonary disease, regardless of HIV serostatus, and other HIV-associated opportunistic pulmonary infections were unusual. Bronchoscopy with bronchoalveolar lavage added little to the diagnosis and thus should not be high-priority procedures for the routine workup in resource-poor areas where tuberculosis is endemic.

AIDS-Related Opportunistic Infections↗

[Clinical and experimental studies on preventing and treating anaphylactic asthma with Zusanli point immunotherapy].

We have studied on preventing and treating anaphylactic asthma with Zusanli (S36) point immunotherapy (ZPIT). Sixty-nine patients were observed. The results showed that the clinical curative effect of ZPIT was not only much higher than that of conventional desensitization therapy, but also the patients' total IgE level was reduced, anti-acarid IgE was lowered, SIgA level was raised, the absolute eosinophilic granulocyte level dropped and pulmonary function recovered. Animal experiment results showed that the ZPIT could more effectively suppress the guinea pigs' anaphylactic asthma allergized by albumin and more obviously resist the guinea pigs' bronchial spasm induced by histamine and acetylcholine than the conventional desensitization therapy and injected normal saline. The immunomodulating action of the ZPIT are elucidated from clinical study and animal experiment in the paper.

Acupuncture Points↗

A receptor kinase-like protein encoded by the rice disease resistance gene, Xa21.

The rice Xa21 gene, which confers resistance to Xanthomonas oryzae pv. oryzae race 6, was isolated by positional cloning. Fifty transgenic rice plants carrying the cloned Xa21 gene display high levels of resistance to the pathogen. The sequence of the predicted protein, which carries both a leucine-rich repeat motif and a serine-threonine kinase-like domain, suggests a role in cell surface recognition of a pathogen ligand and subsequent activation of an intracellular defense response. Characterization of Xa21 should facilitate understanding of plant disease resistance and lead to engineered resistance in rice.

Amino Acid Sequence↗

Incremental doses of dobutamine induce a biphasic response in dysfunctional left ventricular regions subtending coronary stenoses.

BACKGROUND: Dobutamine stress echocardiography has been proposed as a diagnostic tool to identify viable myocardium. How regional wall thickening responds to dobutamine in the ischemic or short-term hibernating myocardium has not been adequately defined. We hypothesized that regional wall thickening would improve initially and subsequently deteriorate with incremental doses of dobutamine in viable myocardial regions supplied by a stenotic coronary artery. This study was undertaken to determine whether this biphasic pattern of regional function characterizes the response of ischemic or hibernating myocardium to dobutamine and to explore the factors and mechanisms that determine this response. METHODS AND RESULTS: Twenty-six pigs in four groups were studied: a control group (n = 5) to assess the response of myocardium perfused by nonstenotic coronary artery to incremental doses of dobutamine, and three experimental groups with a left anterior descending coronary artery stenosis producing acute myocardial ischemia (n = 7), short-term myocardial hibernation for 90 minutes (n = 7), and short-term hibernation for 24 hours (n = 7) to determine the functional and metabolic response to dobutamine under these conditions. Regional coronary flow was reduced to 40% to 60% of baseline, with significant reductions of regional wall thickening as measured by two-dimensional echocardiography and sonomicrometers. An incremental dobutamine infusion from 2.5 to 25 micrograms.kg-1.min-1 increased wall thickening and coronary flow without lactate production in the control group. In the other three groups, during the incremental dobutamine infusion, regional wall thickening improved initially, from 11.4 +/- 7.5% to 19.8 +/- 11.4%, P < .01, at dobutamine doses of 2.5 to 10 (4.5 +/- 2.2) micrograms.min-1.kg-1 but deteriorated subsequently to 5.0 +/- 5.8% at the maximal dose of dobutamine of 12.6 +/- 4.1 micrograms.min-1.kg-1. The initial improvement of regional wall thickening was associated with a small increase in regional coronary flow (from 0.53 +/- 0.18 to 0.68 +/- 0.25 mL.min-1.g-1 myocardium, P < .05) and with regional lactate production. High doses of dobutamine did not further increase regional coronary flow but markedly increased lactate production and induced regional myocardial acidosis (pH 7.26 +/- 0.07). The biphasic pattern of response to dobutamine was observed in each of the three experimental groups. Both peak improvement and peak deterioration occurred earlier and at lower dobutamine dose levels in the group with acute ischemia compared with the group with short-term hibernation for 24 hours (P < .05). CONCLUSIONS: A biphasic response of wall thickening to incremental dobutamine with initial improvement and subsequent deterioration is characteristic of ischemic or short-term hibernating myocardium. The initial low-dose dobutamine infusion improved wall thickening in the ischemic or hibernating myocardial region to a modest level. This initial modest improvement was transient and at the expense of metabolic deterioration of myocardial ischemia, so that at higher doses during prolonged dobutamine infusion, wall thickening deteriorated, lactate accumulated, and myocardial acidosis developed.

Animals↗

Increased cellular uptake of the human immunodeficiency virus-1 Tat protein after modification with biotin.

The human immunodeficiency virus-1 Tat protein can efficiently enter cells when added exogenously in tissue culture. Using the transactivation activity of Tat as a measure of intracellular delivery, we found that the addition of hydrophobic groups to Tat potentiated its uptake. Biotin was the most promising of the reagents tested and we characterized this effect in more detail. When coupled through a cysteine thiol, the addition of a single biotin to Tat increased activity by about six-fold. Increased activity was only seen with reducible biotin analogs, as modification with noncleavable analogs is known to block Tat transactivation activity. Biotin had no effect on Tat uptake when mixed with Tat without cross-linking. Recently, Tat was used as a carrier to direct the uptake of heterologous proteins into cells. We have used RNase as a model system for studying Tat-mediated uptake and found that biotin also increased the delivery of a Tat37-58-RNase conjugate. The increased uptake of Tat and Tat conjugates by addition of hydrophobic groups may significantly enhance the usefulness of Tat as a delivery vehicle, and the approach may be applicable to other systems.

Amino Acid Sequence↗

Interleukin-8 expression by head and neck squamous cell carcinoma.

OBJECTIVE: To test the hypothesis that interleukin-8 (IL-8) is produced by human head and neck squamous cell carcinomas (HNSCCAs) and may therefore be a possible mediator for lymphocyte recruitment and neovascularization by these tumors. METHODS: Nine fresh samples of HNSCCA were analyzed for expression of IL-8 antigen using radioimmunoassay and immunohistochemical staining techniques. Also, four short-term primary cultures of HNSCCA and two continuous HNSCCA cell lines were then analyzed for production of IL-8 expression under both baseline conditions and following stimulation with other cytokines. RESULTS: The IL-8 antigen was detected in all fresh tumor homogenates by radioimmunoassay (5.58 to 331.69 ng of IL-8 per gram of tissue), and immunohistochemical results localized staining predominantly within the tumor cells. Primary cultures of HNSCCA and continuous HNSCCA cell lines produced only low levels of IL-8 (0.04 to 4.49 ng of IL-8 per 10(6) cells) under baseline (unstimulated) conditions. Stimulation of both primary cultures and cell lines with interleukin-1 and tumor necrosis factor induced significant increases in IL-8 antigen, while other cytokines failed to induce a significant increase. CONCLUSIONS: This study demonstrates that IL-8 antigen is expressed by HNSCCA in vivo, and that cultured HNSCCA in vitro can be stimulated to express IL-8 antigen by both interleukin-1 and tumor necrosis factor. Local production of IL-8 by HNSCCA cells, and its regulation by other cytokines, may be important in both the lymphocyte recruitment and tumor neovascularization seen in HNSCCA, and may thus ultimately affect the natural history of the disease.

Carcinoma, Squamous Cell↗

Neuronal activity in the supplementary eye field during acquisition of conditional oculomotor associations.

1. The supplementary eye field (SEF) has been viewed as a premotor cortical field for the selection and control of saccadic eye movements. Drawing on studies of the neighboring premotor cortex, we hypothesized that if the SEF participates in the selection of action based on arbitrary stimulus-response associations, then task-related activity in the SEF should change during the learning of such associations. 2. Rhesus monkeys were operantly conditioned to make a saccadic eye movement to one of four targets (7 deg up, down, left, and right from center) in response to a foveal instruction stimulus (IS). One and only one of those four possible responses was arbitrarily designated "correct" for each IS. The monkeys responded to familiar ISs, four stimuli that remained unchanged throughout training and recording, as well as to novel ISs, which the monkeys had not previously seen. The monkeys initially chose responses to novel stimuli by trial and error, with near chance levels of performance, but quickly learned to select the correct saccade. 3. We studied 186 SEF cells as monkeys learned new visuomotor associations. Neuronal activity was quantified in four task periods: during the presentation of the IS, during an instructed delay period (i.e., after the removal of the IS but before a trigger or "go" stimulus), just before the saccade, and after the saccade during fixation of the target location. The discharge rate in each task period was considered a separate case for analysis, compared with that in a reference period preceding the IS, and eliminated from further analysis if not significantly different. 4. We observed two main categories of activity change during learning, which we termed learning selective and learning dependent. Learning-selective cases showed a significant evolution in activity as the monkeys learned which saccade was instructed by a novel IS, but had no significant modulation during trials with familiar ISs. Many of these cells were virtually inactive on trials with familiar ISs. However, they initially showed dramatic modulation when tested with a novel IS. As the monkey chose the correct saccade (or target) with increasing reliability, the modulation often decremented until the cell was again relatively unmodulated, as observed during familiar-IS trials. These cells usually remained relatively inactive until the monkeys were challenged to start learning another new stimulus-response association. Learning-selective activity was observed in all task periods, and 33 (18%) of the 186 adequately tested SEF cells showed learning-selective activity in one or more task periods.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗