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Biomedical subjects

C W Chen

Publications and source records attributed to C W Chen.

At least 55 records · Page 3Linked to original sources

Predicting factors for outcome of tube thoracostomy in complicated parapneumonic effusion for empyema.

STUDY OBJECTIVES: To determine the predicting factors for outcome of tube thoracostomy in patients with complicated parapneumonic effusion (CPE) or empyema. DESIGN AND SETTINGS: Retrospective chart review over a 55-month period at a tertiary referred medical center. PATIENTS AND MEASUREMENTS: The medical charts of patients with empyema or CPE were reviewed. Data including age, gender, clinical symptoms, important underlying diseases, leukocyte count, duration of preadmission symptoms, interval from first procedure to second procedure, the time from first procedure to discharge (recovery time), the amount of effusion drained, administration of intrapleural streptokinase, chest tube size and position, loculation of pleural effusion, and characteristics and culture results of pleural effusion were recorded and compared between groups of patients with successful and failed outcome of tube thoracostomy drainage. RESULTS: One hundred twenty-one patients were selected for study. One hundred of these patients had received tube thoracostomy drainage with 53 successful outcomes and 47 failed outcomes of chest tube drainage. Nineteen patients received decortication directly, and the other two received antibiotics alone. Univariate analysis showed that pleural effusion leukocyte count, effusion amount, and loculation of pleural effusion were significantly related to the outcome of chest tube drainage. Multiple logistic regression analysis demonstrated that loculation and pleural effusion leukocyte count < or = 6,400/uL were the only independent predicting factors related to failure of tube thoracostomy drainage. CONCLUSIONS: Loculation and pleural effusion leukocyte count < or = 6,400/microL were independent predicting factors of poor outcome of tube thoracostomy drainage. These results suggest that if the initial attempt at chest tube drainage fails, early surgical intervention should be considered in good surgical candidates with loculated empyema or pleural effusion with leukocyte count < or = 6,400/microL.

Aged↗

Varicella pneumonia complicated by acute respiratory distress syndrome in an adult.

Primary varicella infection is uncommon in adults, but carries a higher rate of morbidity and mortality than in children. Pneumonia is the most common complication of primary varicella infection in adults. However, varicella pneumonia complicated with acute respiratory distress syndrome (ARDS) is very rare. We report a case of ARDS secondary to varicella pneumonia in a 26-year-old man with primary varicella. The patient was otherwise healthy and had no evidence of human immunodeficiency virus infection. The initial chest radiograph showed bilateral reticulonodular infiltrates, which quickly evolved to diffuse alveolar consolidations. Arterial blood gas analysis revealed a ratio of arterial partial pressure to fraction of inspired oxygen of 87. Abnormal liver function and thrombocytopenia were also noted. Treatment consisted of mechanical ventilatory support and intravenous administration of acyclovir. His pulmonary condition gradually improved and he was successfully weaned from the ventilator 1 week later. He was discharged on the 15th hospital day with a favorable outcome. His pulmonary function improved progressively, with normal spirometry and lung volumes, but persistent mild impairment of diffusing capacity, 6 months after discharge.

Adult↗

The nephritogenic T cell response in murine chronic graft-versus-host disease.

To investigate mechanisms of cell-mediated events in chronic glomerulonephritis, T cell clones were isolated from kidneys of animals with murine chronic graft-vs-host disease. This systemic disorder is induced in normal (C57BL/6 x DBA/2)F1 recipients (H-2b/d) following transfer of parental (DBA/2) T cells (H-2d). These studies demonstrate that mouse renal (MR) T cells isolated from nephritic kidneys of diseased recipients are host-derived CD4+ alpha/beta+ T cells. Adoptive transfer of a panel of MR clones to naive (C57BL/6 x DBA/2)F1 recipients reveals distinct functional subsets. One subset does not transfer renal disease, and one induces severe renal inflammation and damage. In vitro proliferative responses of nephritogenic MR clones reveal predominant reactivity toward autologous class II MHC (I-Ed/I-Ad) determinants, and selected nephritogenic MR clones preferentially recognize renal Ag preparations derived from normal (C57BL/6 x DBA/2)F1 kidneys. In addition, cytokine profile analysis of MR clones indicates a Th2 pattern with IL-4 and IL-10 expression, although nephritogenic T cell clones also express IFN-gamma. These data suggest that the nephritogenic T cell response in chronic graft-vs-host disease is autoreactive in nature and may be restricted by determinants shared by both graft and host (Iad).

Animals↗

Photochemical reactions of flavor compounds.

Photochemical reaction is a chemical reaction which is initiated by light. In addition to light, photosensitizer and oxygen are the two important factors which contribute to the formation of photochemical products. In this contribution, photochemical reactions of flavor compounds are classified into four categories according to the factors of photosensitizer and oxygen. Photochemical reaction with or without sensitizer in the absence of oxygen and unsensitized photochemical reaction in the presence of oxygen usually involve free radical reactions; while in the presence of oxygen and sensitizer, the singlet oxygen can be generated that then reacts with flavor compounds which contain double bonds to give the oxygenated products.

Dimerization↗

The role of phosphorylation in human estrogen receptor function.

We have studied the role of phosphorylation of the human estrogen receptor (hER) at serine 118, which has been previously identified as a site important for transactivation. We have tested this transactivation in yeast and cell-free transcription assays, and have shown that mutation of serine 118 to alanine results in a 30-40% decrease in hER-dependent transcription. Furthermore, we investigated the functional significance of phosphorylation at this site by hormone binding and DNA binding. The mutation of serine 118 to alanine in the hER caused no decrease in its affinity for either estradiol or an ERE. The mutant receptor had an altered phosphorylation pattern when expressed in COS-1 and Sf9 cells, but not in HeLa cells. Our findings indicate that phosphorylation of serine 118 of the hER plays a role in regulating its transcriptional activity.

Cell-Free System↗

The telomeres of Streptomyces chromosomes contain conserved palindromic sequences with potential to form complex secondary structures.

The chromosomes of the gram-positive soil bacteria Streptomyces are linear DNA molecules, usually of about 8Mb, containing a centrally located origin of replication and covalently bound terminal proteins (which are presumably involved in the completion of replication of the telomeres). The ends of the chromosomes contain inverted repeats of variable lengths. The terminal segments of five Streptomyces chromosomes and plasmids were cloned and sequenced. The sequences showed a high degree of conservation in the first 166-168bp. Beyond the terminal homology, the sequences diverged and did not generally cross-hybridize. The homologous regions contained seven palindromes with a few nucleotide differences. Many of these differences occur in complementary pairs, such that the palindromicity is preserved. Energy-optimized modelling predicted that the 3' strand of the terminal palindromes can form extensive hairpin structures that are similar to the 3' ends of autonomous parvovirus genomes. Most of the putative hairpins have a GCGCAGC sequence at the loop, with the potential to form a stable single C-residue loop closed by a sheared G:A pairing. The similarity between the terminal structures of the Streptomyces replicons and the autonomous parvoviral genomes suggests that they may share some structural and/or replication features.

Base Sequence↗

Subtalar distractional realignment arthrodesis with wedge bone grafting and lateral decompression for calcaneal malunion.

BACKGROUND: The purpose of this study was to evaluate prospectively the efficacy of subtalar distractional realignment arthrodesis in the treatment of calcaneal malunion associated with subtalar arthritis, collapse of height, talonavicular subluxation, malalignment of the heel axis, and widening heel with calcaneofibular abutment. METHODS: Thirty-four patients with severe calcaneal malunion were treated with a lateral approach, lateral decompression, medial subtalar capsulotomy, and distraction and realignment of the subtalar joint with an anteriorly and laterally tapered wedge bone graft. The patients were evaluated with a functional rating scale and radiographs, both before and after surgery. RESULTS: Thirty-two of the 34 patients were evaluated at a mean of 71 months (range, 60-92 months) after the arthrodesis. Solid subtalar fusion was achieved in 31 of the 32 patients. The average gain of subtalar distraction was 12 mm. Neutral or mild valgus alignment was achieved in 26 of the 32 patients. The mean postoperative score (83) showed significant improvement over the mean preoperative score (47). Overall, the functional rating scale revealed excellent or good results in 26 patients and fair results in 6 patients. CONCLUSION: Coupled with wedge bone grafting, the subtalar distractional realignment arthrodesis achieved restoration of hindfoot height and axial alignment with a good union rate and significant improvement in the majority of patients with calcaneal malunion.

Adult↗

Dose-response relationship and irreversible obstructive ventilatory defect in patients with consumption of Sauropus androgynus.

STUDY OBJECTIVES: To determine the dose-response aspect of pulmonary function impairment in patients with consumption of Sauropus androgynus for weight reduction. METHODS: A questionnaire and pulmonary function tests were performed in 194 patients with a history of consumption of S androgynus with or without chest symptoms. Patients with obstructive ventilatory defect received follow-up spirometry 22 to 24 months after beginning consumption of the vegetable. RESULTS: Data from 178 patients were analyzed. Patients generally consumed 150 g of S androgynus daily as raw juice (60.7%), sauteed (16.9%), mixed preparation (20.8%), or boiled (1.7%) for various periods of time. We divided patients into five groups according to the total dose consumed (group A, 0 to 1,799 g; group B, 1,800 to 3,599 g; group C, 3,600 to 5,399 g; group D, 5,400 to 7,199 g; and group E, > or =7,200 g). The frequency of obstructive ventilatory defect was higher in the high-dose group than in the low-dose group (A, 4/43=9.3%; B, 13/64=20.3%; C, 14/32=43.8%; D, 5/12=41.7%; and E, 13/27=48.1%; p < 0.01). In total, 49 patients (27.5%) had moderate to severe obstructive ventilatory defects without bronchodilator response. The FEV1 and FEV1 percent predicted in these 49 patients were 0.96+/-0.38 L (mean+/-SD) and 41.8+/-16.9%, respectively. Sixty-five percent of these 49 patients began to suffer from dyspnea in the third, fourth, or fifth month after taking the vegetable and no patient began to develop dyspnea later than 7 months after beginning consumption of the vegetable. Using stepwise multiple regression, we found that the FEV1 percent predicted was negatively associated with the total dose ingested (r=0.24, p < 0.01). Follow-up spirometry showed that the obstructive ventilatory defect was irreversible in all patients. CONCLUSIONS: Consumption of S androgynus can result in moderate to severe obstructive ventilatory defect within 7 months, and the disorder was irreversible in the observation period for 22 months.

Adolescent↗

Respiratory mechanics before and after hemodialysis in mechanically ventilated patients.

Hemodialysis, which leads to negative fluid balance, is often required in mechanically ventilated patients with renal failure. We conducted a prospective study on the influence of hemodialysis on the respiratory mechanics in 14 mechanically ventilated patients (10 men, 4 women, mean age 70.1 +/- 8.1 yr) with various causes of renal failure requiring hemodialysis in an intensive care unit. Respiratory mechanics were measured before and after hemodialysis using the interrupter technique under constant flow and constant volume. The values of several parameters of respiratory mechanics were significantly lower after hemodialysis: peak airway pressure (26.97 +/- 4.62 vs 23.45 +/- 4.13 cmH2O), airway pressure at zero flow (23.81 +/- 4.18 vs 21.50 +/- 3.79 cmH2O), airway plateau pressure (18.56 +/- 3.70 vs 16.48 +/- 3.07 cmH2O), and intrinsic positive end-expiratory pressure (4.03 +/- 2.90 vs 2.65 +/- 1.84 cmH2O). Minimal respiratory resistance and maximal respiratory resistance were significantly decreased after hemodialysis (4.38 +/- 1.26 vs 2.99 +/- 1.00 cmH2O/L/s and 9.93 +/- 2.50 vs 8.39 +/- 2.43 cmH2O/L/s, respectively), but effective additional respiratory resistance and static respiratory compliance were not. Significant correlations were found between body weight reduction by hemodialysis and changes in minimal respiratory resistance (r = 0.758, p < 0.01), maximal respiratory resistance (r = 0.544, p < 0.05), and static respiratory compliance (r = 0.703, p < 0.01). We conclude that hemodialysis significantly alters the respiratory mechanics in mechanically ventilated renal failure patients and that the alteration may be related to the negative fluid balance caused by hemodialysis.

Aged↗

Transforming growth factor beta1 attenuates ceramide-induced CPP32/Yama activation and apoptosis in human leukaemic HL-60 cells.

Ceramide, a product of sphingomyelin turnover, is a novel lipid second messenger that mediates important cellular functions including proliferation, differentiation and apoptosis. This study demonstrates that the CPP32/Yama protease was activated during apoptosis induced by the membrane-permeable second messenger C2-ceramide in HL-60 cells. We also found that the addition of a specific tetrapeptide inhibitor of CPP32/Yama, Ac-DEVD-CHO, provided an effective protection against ceramide-induced cell death. These results suggested that CPP32/Yama has a central role in ceramide-mediated apoptosis. Furthermore a wide variety of cytokines were examined for their effect on ceramide-induced apoptosis. Only transforming growth factor beta1 (TGF-beta1) (1 ng/ml) exerted significant prevention of apoptosis induced by C2-ceramide, or by sphingomyelinase (increases intracellular ceramide). Consistently, TGF-beta1 abrogated the cleavage of poly(ADP-ribose) polymerase and the production of the CPP32/Yama active subunit, p17. However, TGF-beta1 treatment did not cause growth inhibition or alter the level of cyclin-dependent kinase inhibitor p27. It suggests that the preventive effect of TGF-beta1 is not mediated by growth arrest. Interestingly, we found that TGF-beta1 prevented the C2-ceramide-caused decrease of Bcl-2 protein. We thus propose that TGF-beta1 rescues ceramide-induced cell death, possibly by maintaining the constant level of Bcl-2, thereby abolishing CPP32/Yama protease activation.

Apoptosis↗

Asymmetric expression of Notch/Delta/Serrate is associated with the anterior-posterior axis of feather buds.

We studied the roles of Notch, Delta, and Serrate in vertebrate epithelial appendage morphogenesis using feather as a model and found the following. (1) C-Notch-1, C-Delta-1, and C-Serrate-1 are not expressed at the early placode stage and are therefore not involved in the determination of bud versus interbud compartments. (2) From symmetric short buds to asymmetric long buds, C-Delta-1 and C-Serrate-1 are expressed in the posterior bud mesenchyme in a nested fashion, while C-Notch-1 is expressed as a stripe perpendicular to the anterior-posterior (A-P) axis and positioned posterior to the midpoint. (3) Epithelial-mesenchymal recombination with rotation led to the disappearance of these genes followed by their reappearance with new positions appearing to predict their new morphological orientation. (4) Conditions leading to branched buds (e.g., recombination of later buds) show polarized staining patterns before branching occurs. (5) Conditions leading to symmetrical round buds (e.g., treated with the protein kinase A agonist forskolin) suppress expression of all three genes. These results lead us to hypothesize that Notch, Delta, and Serrate are involved in establishing the A-P asymmetry of feather buds.

Animals↗

Transcriptional activation of the human estrogen receptor by DDT isomers and metabolites in yeast and MCF-7 cells.

In this study, we determined whether the DDT isomers p,p'-DDT [1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane], o,p'-DDT [1,1,1-trichloro-2(p-chlorophenyl)-2-(o-chlorophenyl)ethane], and their metabolites p,p'-DDD [1,1-dichloro-2,2-bis(p-chlorophenyl)ethane], o,p'-DDD [1,1-dichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)ethane], p,p'-DDE [1,1,-dichloro-2,2-bis(p-chlorophenyl)ethylene], o,p'-DDE [1,1-dichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)ethylene], and p,p'-DDA [2,2-bis(p-chlorophenyl)acetic acid], could bind to and transcriptionally activate the human estrogen receptor (hER). Novel results from competitive binding assays showed that o,p'-DDD, o,p'-DDE, and p,p'-DDT, as well as the established environmental estrogen o,p'-DDT, were able to bind specifically to the hER with approximately 1000-fold weaker affinities for the hER than that of estradiol. In contrast, only o,p'-DDT, but not p,p'-DDT, bound to the rat estrogen receptor. Moreover, two yeast expression-reporter systems, constructed to test if the DDT isomers and metabolites could transcriptionally activate the hER, demonstrated that an o,p'-DDT metabolite could transactivate the hER or LexA-hER fusion protein with just a 140- to 300-fold weaker potency than that of estradiol. The DDT isomers and metabolites that bound the hER in vitro triggered estrogen receptor-mediated transcription of the lacZ reporter gene in the yeast systems. Furthermore, the DDT isomers and metabolites that transactivated the hER elicited an additive response when given together or with estradiol. The DDT isomers and metabolites that triggered transcription of the yeast expression-reporter systems also stimulated two estrogenic endpoints in estrogen-responsive MCF-7 cells: the induction of the progesterone receptor and the down-regulation of the hER. Thus, in MCF-7 cells and in yeast expression-reporter systems, certain DDT isomers and metabolites act directly as agonists and transactivate the hER at concentrations found in human tissues.

Animals↗

Comparative effects of L-NOARG and L-NAME on basal blood flow and ACh-induced vasodilatation in rat diaphragmatic microcirculation.

1. The effects of N omega-nitro-L-arginine (L-NOARG) and N omega-nitro-L-arginine methyl ester (L-NAME) on diaphragmatic microcirculation in male Sprague-Dawley rats were assessed under basal conditions and after acetylcholine (ACh) stimulation. In addition, L-arginine (L-arg) was used with the aim of preventing L-NOARG and L-NAME from inhibiting ACh-induced vasodilatation, in order to explore the possibility that L-NOARG is not only a nitric oxide (NO) synthase inhibitor but also a muscarinic receptor antagonist. 2. Male Sprague-Dawley rats were anaesthetized with urethane and mechanically ventilated. The left hemi-diaphragm of each rat was prepared and microvascular blood flow was recorded during continuous superfusion with bicarbonate-buffered prewarmed Ringer solution by using laser-Doppler flowmetry. The drugs were topically applied to the surface of the hemi-diaphragm. 3. Baseline microvascular blood flow was unaffected after 15 min superfusion with any one of the following agents: L-NOARG (0.1 mM). L-NAME (0.1 mM), L-arg (10 mM). 4. ACh (0.03 mM, 0.1 mM and 0.3 mM) elicited a significant increase of microvascular blood flow (171 +/- 16%, 214 +/- 55%, and 323 +/- 68% of baseline values, respectively), via interaction with the muscarinic receptor, for the vasodilator response was severely inhibited by 15 min superfusion with atropine (0.3 mM). 5. Following 15 min superfusion with either of the L-arg analogues (0.1 mM), the ACh-induced vasodilator response was significantly inhibited. Pretreatment with L-arg (10 mM) for 5 min, followed by co-administration of L-arg (10 mM) and L-NOARG (0.1 mM) for another 15 min significantly prevented the inhibitory effect of L-NOARG or ACh-induced vasodilatation. However, a similar pretreatment schedule with L-arg failed to prevent L-NAME from exerting its inhibitory effect. 6. Neither of the L-arg analogues potentiated sodium nitroprusside (10 microM and 30 microM)-induced vasodilatation. However, adenosine (0.1 mM)-induced vasodilatation was slightly but significantly attenuated by either L-NOARG (0.1 mM) or L-NAME (0.1 mM), an effect which was prevented by L-arg (10 mM). 7. In conclusion, an increase in endothelium-dependent blood flow stimulated by ACh may occur in diaphragmatic microcirculation of anaesthetized rats independently of low baseline NO activity. The results also suggest that L-NAME has muscarinic receptor antagonist action in addition to its ability to inhibit NO synthase. Thus, we suggest that L-NAME should not be used as a specific NO synthase inhibitor in the rat diaphragm in situations in which there is potential for muscarinic receptors to be stimulated.

Acetylcholine↗

Vasomotion in rat diaphragm microcirculation at rest and during stepwise arterial pressure reduction.

The effect of haemorrhagic hypotension on the incidence, frequency and relative amplitude of vasomotion in rat diaphragm microcirculation was assessed by laser Doppler flowmetry (LDF). Graded bleeding to four hypotension levels (80, 60, 40 and 30% of the control state) were performed in 24 Sprague-Dawley rats. The incidence of vasomotion was 83% in the control state, 96% at the 80% level, 100% at the 60% level, 96% at the 40% level, and 46% at the 30% level. The median fundamental frequency of vasomotion determined manually during the control state and at the hypotension levels (in descending order) was 4.11 (range, 3.29-5.58) cycles min-1 (cpm), 4.48 (3.21-5.92) cpm, 4.20 (3.5-5.56) cpm, 4.01 (3.33-5.36) cpm, 3.71 (3.25-4.49) cpm (P < 0.01 from the fundamental frequency at 80 and 60% hypotension levels). The median relative amplitudes determined manually during the control state and descending hypotension levels were 44.5% (range, 24.9-135.9%), 69.4% (26.6-147.2%), 84.0% (40.3-177.1%) (P < 0.01 from resting and last stage of bleeding), 90.40% (26.2-189.6%) (P < 0.01 from resting and last stage of bleeding), 69.2% (35.6-93.2%). We concluded first that during the resting condition, vasomotion was frequently present in diaphragm microcirculation, which is distinct from other vascular beds of skeletal muscles. Second, the relative amplitude of vasomotion during haemorrhagic hypotension plotted against decreasing blood pressure exhibited a reverse U-shaped curve with a maximum at 40-60% of the control blood pressure, while the frequency of vasomotion remained relatively constant until the last stage of haemorrhage and centred around 3-5 cpm.

Animals↗

Instability of artificially circularized chromosomes of Streptomyces lividans.

The chromosomes of Streptomyces species are linear molecules, containing long terminal inverted repeats and covalently bound terminal proteins. These chromosomes undergo spontaneous deletions of the terminal sequences at high frequencies and become circularized in several cases examined. Artificial circularization of the Streptomyces lividans chromosome was also achieved by targeted recombination in vivo, in which the terminal inverted repeats of the chromosome were connected by a kanamycin resistance gene (aphII). Under kanamycin selection, the circularized chromosomes harboured tandem amplifications of a 20.2 kb sequence that included the aphII gene flanked by direct repeats and deletions nearby. On release from kanamycin selection, the aphII amplifications and the neighbouring sequences were deleted from the chromosomes, rendering all the cultures kanamycin sensitive. The chloramphenicol resistance gene, which was prone to deletion in wild-type S. lividans, became much more stable in the kanamycin-sensitive derivatives. These results indicate that the telomeres and/or certain terminal sequences may be involved in the structural instability of Streptomyces chromosomes.

Chromosomes, Bacterial↗

Biochemical and molecular changes at the cellular level in response to exposure to environmental estrogen-like chemicals.

Estrogen-like chemicals are unique compared to nonestrogenic xenobiotics, because in addition to their chemical properties, the estrogenic property of these compounds allows them to act like sex hormones. Whether weak or strong, the estrogenic response of a chemical, if not overcome, will add extra estrogenic burden to the system. At elevated doses, natural estrogens and environmental estrogen-like chemicals are known to produce adverse effects. The source of extra or elevated concentration of estrogen could be either endogenous or exogenous. The potential of exposure for humans and animals to environmental estrogen-like chemicals is high. Only a limited number of estrogen-like compounds, such as diethylstilbestrol (DES), bisphenol A, nonylphenol, polychlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (DDT), have been used to assess the biochemical and molecular changes at the cellular level. Among them, DES is the most extensively studied estrogen-like chemical, and therefore this article is focused mainly on DES-related observations. In addition to estrogenic effects, environmental estrogen-like chemicals produce multiple and multitype genetic and/or nongenetic hits. Exposure of Syrian hamsters to stilbene estrogen (DES) produces several changes in the nuclei of target organ for carcinogenesis (kidney): (1) Products of nuclear redox reactions of DES modify transcription regulating proteins and DNA; (2) transcription is inhibited; (3) tyrosine phosphorylation of nuclear proteins, including RNA polymerase II, p53, and nuclear insulin-like growth factor-1 receptor, is altered; and (4) DNA repair gene DNA polymerase beta transcripts are decreased and mutated. Exposure of Noble rats to DES also produces several changes in the mammary gland: proliferative activity is drastically altered; the cell cycle of mammary epithelial cells is perturbed; telomeric length is attenuated; etc. It appears that some other estrogenic compounds, such as bisphenol A and nonylphenol, may also follow a similar pattern of effects to DES, because we have recently shown that these compounds alter cell cycle kinetics, produce telomeric associations, and produce chromosomal aberrations. Like DES, bisphenol A after metabolic activation is capable of binding to DNA. However, it should be noted that a particular or multitype hit(s) will depend upon the nature of the environmental estrogen-like chemical. The role of individual attack leading to a particular change is not clear at this stage. Consequences of these multitypes of attack on the nuclei of cells could be (1) nuclear toxicity/cell death; (2) repair of all the hits and then acting as normal cells; or (3) sustaining most of the hits and acting as unstable cells. Proliferation of the last type of cell is expected to result in transformed cells.

Animals↗

Trabeculectomy with multiple applications of mitomycin-C in monkeys with experimental glaucoma.

To inhibit the wound healing process and to achieve a better intraocular pressure lowering effect, we applied mitomycin-C (MMC) topically in trabeculectomy at different time sequences. In this experiment, a model of glaucoma trabeculectomy combined with light microscopic autoradiography study was used to evaluate the clinical and histological effects and the time course of cellular incorporation of tritiated thymidine. This study utilized twelve eyes (divided into three groups) of six monkeys with experimental glaucoma. Group I received 0.08 ml subconjunctival injection of 0.02 mg/ml MMC 24 to 36 hours prior to trabeculectomy. Group II received intraoperative topical application of 0.27 mg/ml MMC for 4 minutes. Group III received the same treatment as group II, along with pre-operative and repeated post-operative conjunctival applications of 0.4 mg/ml MMC for 10 minutes. Surgical success, IOP < 21 mmHg, lasted for a median of 8 days in group I, 56 days in group II and 75 days in group III. Compared with group I, cellular proliferation was significantly inhibited in group II and mostly inhibited in group III. No significant ocular toxicity or profound hypotony was observed. Histological examination of group III on the 90th day after operation showed patent scleral tunnel and hypocellular loose connective tissue in the conjunctival bleb. These results demonstrated that a series of pre-, intra- and repeated postoperative topical applications of mitomycin-C had a prolonged effect in inhibiting wound healing after trabeculectomy in monkeys.

Animals↗

Analog transmission line model for simulation of systemic circulation.

A simple four-tube arteries-microvessels-veins system which simulates a more realistic loading for human circulation was built using transmission line network. Hemodynamic data from literature are used in the fluid-circuit analogy, and the flow leakage and viscoelastic properties of the blood vessels have been considered. The effect of veins on the input impedance spectrum was found to be negligibly small above 0.5 Hz. The predicted input impedance spectra agree reasonably well with the published measurements both in shape and magnitude. Parametric analysis shows that the changes of vascular properties in the lower body affect the first minimum, and the changes in the upper body influence the second minimum. The blood flow in and out of kidney and liver dominates the aortic impedance from 0 to 5 Hz. Decreasing capacitance (i.e., increasing arterial stiffness due to aging), reducing the lumen area, or decreasing the length of blood vessels result in an increase in the impedance modulus, and the first minimum shift to a higher frequency which agree well with experiments. In the current model, the pressure, flow waveform, and local impedance can be predicted at any location along the circulatory tree. The characteristic of arterial pulse propagation resembles published measurements.

Arteries↗