Biomedical subjects

Y Koh

Publications and source records attributed to Y Koh.

At least 37 records · Page 2Linked to original sources

PubMed2001

In vitro synergistic interactions between the cisplatin analogue nedaplatin and the DNA topoisomerase I inhibitor irinotecan and the mechanism of this interaction.

Among the numerous clinical regimens used in combination chemotherapy, synergy is particularly marked in combinations containing cisplatin (CDDP). However, the clinical use of CDDP is sometimes limited due to its nephrotoxicity. Nedaplatin (NDP) is a second-generation platinum complex with reduced nephrotoxicity that may substitute for CDDP or even surpass it for use in combination with other drugs. We investigated the effects of combinations of NDP and other anticancer drugs on the growth of human small cell lung cancer cells (SBC-3) and non-small cell lung cancer cells (PC-14) using a three-dimensional analysis model. Among the combinations tested, the combination of NDP and irinotecan (CPT-11) showed the most marked synergistic interaction, and the synergism has also been observed against PC-14 cells. With regard to treatment schedule, a remarkable synergistic interaction was produced by concurrent exposure to NDP and CPT-11. On the other hand, sequential exposure to the two drugs led only to additivity. To analyze the interaction between the drugs, the effect of NDP on the 7-ethyl-1-hydroxy-CPT (the active form of CPT-11)-induced inhibitory effect on DNA topoisomerase I was examined. The topoisomerase I-inhibitory effect of 7-ethyl-1-hydroxy-CPT was enhanced 10-fold in the presence of NDP at microgram/milliliter concentrations. These biochemical interactions might be responsible for the synergistic interaction between NDP and CPT-11. These results suggest that the combination of NDP with CPT-11 may be clinically useful for the chemotherapy of lung cancer.

Antineoplastic Agents↗

PubMed2001

The prognosis of respiratory failure in patients with tuberculous destroyed lung.

SETTING: The medical intensive care unit of a tertiary referral hospital. OBJECTIVE: To determine the prognosis of patients whose lungs are damaged by previous and/or present tuberculosis infection and who have subsequently been presented with acute respiratory failure requiring mechanical ventilation. DESIGN: A consecutive series of 38 patient cases with retrospective data analysis. RESULTS: Pulmonary function test results for tests performed within the previous year were made available in 21 of the 38 cases (55%). These showed a mean (+/- SD) forced vital capacity (FVC) of 1.52 +/- 0.46 L (41.0 +/- 14.5% predicted), a forced expiratory volume/second (FEV1) of 0.77 +/- 0.18 L (29.3 +/- 13.6% predicted), and an FEV1/FVC ratio of 55.1 +/- 16.2%. The acid-fast bacilli (AFB) positive group had a significantly higher mortality and more severe lung destruction when compared with the AFB-negative group. Patients with positive AFB were significantly more hypocapnic than those with negative AFB (6.4 +/- 2.7 vs. 9.3 +/- 3.9 kPa, P = 0.020). In multivariate analysis, the level of PaCO2 on admission was identified as the only significant prognostic index (OR 0.76, 95%CI 0.60-0.96). CONCLUSION: Patients with positive AFB smears or cultures may have higher mortality rates than those with negative AFB in the tuberculosis destroyed lung patients with acute respiratory failure. A higher PaCO2 measurement could indicate a better survival rate in this group of patients.

Adult↗

PubMed2000

Purification and cDNA cloning of salmorin that inhibits fibrinogen clotting.

A new protein, salmorin, that inhibits fibrinogen clotting was purified to homogeneity from the snake venom of Agkistrodon halys brevicaudus. Salmorin was characterized to be a heterodimeric protein composed of 15 kDa and 14 kDa subunits. Purified salmorin inhibited not only thrombin-induced fibrinogen clotting but also factor Xa-induced prothrombin activation. Experimental evidence indicated that the hetero-dimeric protein does not bind to the thrombin catalytic site but binds to thrombin and prothrombin exosites. Analyses of the cDNA sequences encoding the two separate polypeptide chains revealed that the mature subunits are composed of 131 and 122 amino acids, respectively. In the isolated cDNAs, N-termini of both chains are preceded by hydrophobic signal peptides of 23 residues. The deduced amino acid sequence exhibited considerable identity with other snake venom C-type lectin-like proteins derived from various snake venoms.

Agkistrodon↗

PubMed2000

Molecular determinants of UCN-01-induced growth inhibition in human lung cancer cells.

UCN-01 (7-hydroxystaurosporine) inhibits the growth of various malignant cell lines in vitro and in vivo. In this study, a human small cell lung carcinoma subline resistant to UCN-01, SBC-3/UCN, was established and characterized. SBC-3/UCN cells showed 8-fold greater resistance to the UCN-01-induced growth-inhibitory effect than the parent cells, SBC-3. No UCN-01-induced G1 accumulation in SBC-3 cells was observed in SBC-3/UCN cells and decreased expression of phosphorylated RB protein was found in SBC-3 cells. Neither basal expression nor induction of p21(Cip1) by UCN-01 treatment was detected in the SBC-3/UCN cell line. An inhibitory effect of UCN-01 on CDK2 activity, which is mediated by p21(Cip1)/CDK2 complex formation upon UCN-01 treatment, was observed in SBC-3 but not in SBC-3/UCN cells. SBC-3/UCN showed higher CDK6 activity than SBC-3 cells. UCN-01 did not inhibit the CDK4 and CDK6 activities in both cells. We screened the cell cycle regulatory molecules associated with G(1)/S progression and found a remarked decrease in interferon regulatory factor 1 (IRF-1), which is known to cooperate with p53 in p21(Cip1) induction. Our results suggest that p21(Cip1) regulation via the IRF-1-associated pathway may represent a major determinant of UCN-01-induced growth inhibition in human lung cancer cells.

Alkaloids↗

PubMed2000

Microwave coagulation therapy for hepatocellular carcinoma.

The efficacy and safety of microwave coagulation therapy (MCT) in patients with hepatocellular carcinoma (HCC) and impaired hepatic reserve were studied. Preoperative background factors, postoperative results, and prognostic factors were compared in 51 patients who underwent hepatic resection (HR group) and 38 patients who underwent microwave coagulation therapy (MCT group). Before surgery, measures of hepatic function, including level of albumin (P = 0.0072), prothrombin time (P<0.0001), hepaplastin test (P = 0.0088), and the radioactivity of technetium-99m galactosyl-human serum albumin 15 min in the liver after injection divided by that in both liver and heart (P <0.0001) were significantly lower in the MCT group than in the HR group. The indocyanine green dye retention rate at 15 min was significantly greater (P<0.0001) in the MCT group than in the HR group, and a significant difference was noted in Child-Pugh grade between the groups (P<0.0001). Operative time (P = 0.0014) and blood loss during surgery (P = 0.0005) were significantly lower in the MCT group than in the HR group. In contrast, no significant differences were recognized between the groups in the changes in postoperative liver function, or in the rates of morbidity, mortality, local recurrence, and survival. Moreover, the type of treatment (HR or MCT) was not a prognostic factor. The results indicate that MCT can be used safely as an alternative to hepatic resection in patients with poor liver function without reducing the efficacy of local control.

Aged↗

PubMed2000

Characteristics of lung cancer in Korea, 1997.

The high proportion of smokers and the incidence of advanced, unresectable lung cancer in Korea were examined to aid the development of a national anti-smoking program and the early detection of lung cancer. Koreans are a single racial group with a high smoking rate among men and a contrastingly low smoking rate among women. This report documents a retrospective investigation conducted by The Korean Academy of Tuberculosis and Respiratory Disease into the characteristics of all lung cancers diagnosed between 1 January 1997 and 31 December 1997 in Korea. Among the 3794 patients included in this study, 76.8% were smokers and, in particular, 89.8% of the males were smokers. Squamous cell carcinoma was the most frequent type of lung cancer encountered (44.7%), followed by adenocarcinoma (27.9%). The smoking rate in the case of adenocarcinoma was significantly lower than that found in both squamous cell carcinoma and small cell cancer. The most common symptom was a cough. Only 7.2% of patients were asymptomatic. Bronchoscopic biopsy has a primary role in the diagnosis of squamous cell carcinoma and small cell cancer, but percutaneous needle biopsy has a more important role in the case of adenocarcinoma. Two-thirds of the nonsmall cell lung cancer patients were detected in the unresectable advanced stages (IIIB and IV). In contrast to other countries, squamous cell carcinoma is still the most frequent type of lung cancer in Korea. The high proportion of smokers and the incidence of advanced, unresectable lung cancer at diagnosis have urged development of a national anti-smoking program to promote the cessation of smoking and the early detection of lung cancer.

Adult↗

PubMed2000

Multi-organ failure caused by reactivated coccidioidomycosis without dissemination in a patient with renal transplantation.

OBJECTIVE: The acute respiratory failure caused by pulmonary coccidioidomycosis without dissemination is an extremely unusual event. CASE REPORT: We report a 47-year-old renal transplanted man with a reactivated pulmonary coccidioidomycosis, whose clinical course presented as fulminant respiratory failure, disseminated intravascular coagulation and profound hypotension mimicking bacterial pneumonia and septic shock. Lung biopsy showed conglomerated necrotizing granulomas containing many spherules filled with endospores of Coccidioides immitis. CONCLUSION: Coccidioidomycosis should be included in the differential diagnosis of acute sepsis, particularly in an immunocompromised host who has travelled in an endemic area.

Coccidioidomycosis↗

PubMed2000

Partial liquid ventilation shows dose-dependent increase in oxygenation with PEEP and decreases lung injury associated with mechanical ventilation.

PURPOSE: The purpose of this article is to evaluate the effect of positive end-expiratory pressure (PEEP) during partial liquid ventilation (PLV) and to investigate if lung damage associated with mechanical ventilation can be reduced by PLV. MATERIALS AND METHODS: Twenty-two New-Zealand white rabbits were ventilated in pressure-controlled mode maintaining constant tidal volume (10 mL/kg). Lung injury was induced by repeated saline lavage (PaO2 < 100 mm Hg). Two incremental PEEP steps maneuvers (IPSMs) from 2 to 10 cm H2O in 2 cm H2O steps were performed sequentially. The control group received the first IPSM in the supine position and were turned prone for the second IPSM. In the PLV group (n = 7), 12 mL/kg of perfluorodecalin was instilled after lung injury before the two IPSMs. The early prone group (n = 7) received both IPSMs in the prone position. Parameters of gas exchange, lung mechanics, and hemodynamics as well as pathology were examined. RESULTS: During the first IPSM, the PLV group showed a significant increase in PaO2 after instillation of perfluorodecalin (P < .05) and then showed a dose-dependent increase in PaO2 with PEER. The control and EP groups showed improvement in PaO2 only at higher PEEP, eventually showing no intergroup differences at PEEP of 10 cm H2O. During the second IPSM only the PLV group retained its ability to increase PaO2 to the level obtained during the first IPSM (P < .05 compared with control and EP groups). During the first IPSM all three groups showed increasing trend in static compliance (Cst) with PEEP peaking at PEEP of 8 cm H2O. During the second IPSM, only the PLV group showed increase in static compliance with PEEP (P < .05 compared with other groups). Lung histology revealed significantly less hyaline membrane formation in the PLV group (P < .05). CONCLUSION: PLV shows dose-dependent increase in oxygenation with PEEP and may reduce lung damage associated with mechanical ventilation.

Analysis of Variance↗

PubMed2000

Effect of an additional 1-hour T-piece trial on weaning outcome at minimal pressure support.

PURPOSE: The purpose of this article was to investigate the effect of an additional 1-hour T-piece trial at the level of minimum pressure support (PSmin) on weaning outcome. MATERIALS AND METHODS: Open, randomized, prospective study of 44 patients who had received mechanical ventilation for more than 3 days.Thirty-six patients satisfied the protocol. There were 42 weaning trials. The patients were randomized into an intervention group (additional 1-hour period of T-piece trial) and a control group (extubation directly) at PSmin. Blood gas analysis and estimation of respiratory and hemodynamic variables were performed at the 15 cm H2O level of pressure support. Measurements were repeated at PSmin and during weaning process (in intervention group). RESULTS: Mean PSmin level was 7.6 (+/- 1.9) cm H2O. There were no differences in total ventilation time (TVT), acute physiology and chronic health evaluation (APACHE) II score, nutritional indices, and respiratory mechanics on PSmin between the two groups. The weaning success rate and the reintubation rate were similar for the intervention group (55% and 18%, respectively) and control group (70% and 20%, respectively). Work of breathing, pressure time product, and tidal volume significantly worsened after a 1-hour T-piece trial when compared with those values measured at PSmin in the intervention group (P < .05). For the combined patient sample, TVT and tidal volume at PSmin were significantly different between the patients with weaning success (246 +/- 195 hours, 0.43 +/- 0.11 L) and those with weaning failure (407 +/- 248 hours, 0.35 +/- 0.10 L) (P < .05 in each). CONCLUSION: There were no advantages in weaning outcome by the addition of a 1-hour T-piece trial compared with prompt extubation at PSmin.

APACHE↗

PubMed2000

Risk factors for the development of hemodynamically significant cardiac arrhythmias in patients with mechanical ventilation.

PURPOSE: The purpose of this article was to identify the risk factors related to development of hemodynamically significant cardiac arrhythmias in patients with mechanical ventilation. MATERIALS AND METHODS: Holter recording and echocardiogram were performed within 24 hours of ventilator initiation in patients on mechanical ventilation (MV) owing to respiratory failure (RF) from various reasons. RESULTS: From 68 patients, hemodynamically significant cardiac arrhythmias were detected in 18 patients (26.5%). Initial mean arterial pressure, maximal heart rate, and initial pH were identified as risk factors for hemodynamically significant cardiac arrhythmias. Additionally, the patients with pressure-controlled ventilation as an initial ventilatory mode developed hemodynamically significant cardiac arrhythmias less frequently than the patients with other modes (15.8% vs. 40%, P = .03). In multivariate analysis, initial mean arterial pressure (< 70 mm Hg, odds ratio [OR]: 5.5; 95% confidence interval [CI]: 1.2 to 24.2, P = .026), maximal heart rate (> 120/min, OR: 19.7; 95% CI: 2.0 to 190.9, P = .01), and pressure-controlled ventilation (OR: 0.13; 95% CI: 0.03 to 0.55, P = .006) were associated with the development of hemodynamically significant cardiac arrhythmias. CONCLUSIONS: These findings suggest that during the early stages of mechanical ventilation with acute respiratory failure, hemodynamically significant cardiac arrhythmias are directly associated with tachycardia (> or = 120/min), initial MAP (<70 mm Hg), and, inversely, the initial use of pressure-controlled ventilation.

APACHE↗

PubMed2000

Closing volume influences the postural effect on oxygenation in unilateral lung disease.

In normal adults, both blood flow and ventilation are distributed preferentially to the dependent lung zones. In adults with unilateral lung disease, arterial oxygenation improves when they are positioned with their good lung down because of improved matching of ventilation and perfusion. When the closing volume is increased, dependent airways are closed during tidal breathing, so that reduced ventilation-perfusion ratio and hypoxia develops and ventilation is preferentially distributed to the upper lung zones. We undertook an observational study on the effects of lateral recumbency on arterial oxygenation in adult patients with unilateral lung disease and tested the hypothesis that oxygenation in lateral recumbency might be influenced by an increase in closing volume. Arterial blood gases were analyzed in the supine, right and left lateral decubitus positions and the AaPO(2) was calculated in 44 randomly selected patients 49.9 +/- 18.7 yr of age with unilateral pneumonia (23 cases) or pulmonary tuberculosis (21 cases). In 26 patients, individual Pa(O(2)) with the normal lung in the dependent position was higher than that with the diseased lung; the opposite was true for 18 patients. The difference in Pa(O(2)) and AaPO(2) between the two positions was statistically significant in both groups. In 16 patients (10 men and six women 49.2 +/- 18.2 yr of age), we measured closing volume and determined the fractional ventilation to each lung by (133)Xe lung scan in the three positions. In these 16 patients, the difference in Pa(O(2)) between the normal and the diseased lung in the dependent position was related significantly to the difference in the fractional ventilation going to the normal lung between the dependent and the supine position (r = 0.642, p = 0. 007). The latter was related significantly to the % predicted closing volume (CV/VC) (r = -0.597, p = 0.015). This study has shown that closing volume, as well as posture, might be involved in determining oxygenation in lateral recumbency in patients with unilateral lung disease.

Adolescent↗

PubMed2000

An optimal dose of perfluorocarbon for respiratory mechanics in partial liquid ventilation for dependent lung-dominant acute lung injury.

BACKGROUND: Despite increasing knowledge about partial liquid ventilation (PLV), the optimal dose of perfluorocarbon (PFC) is not yet established. Because there exist normal regions in the lung with ARDS and because PLV in the normal lung results in worsened gas exchange, we postulated that the optimal dose of PFC for PLV may be less than the functional residual capacity (FRC) dose in the lung with limited disease. DESIGN AND SETTING: Animal study at the Asan Institute for Life Sciences, Seoul, Korea. SUBJECTS: Twelve rabbits in which dependent lung-dominant lung injury was created by a modified saline solution lavage. INTERVENTIONS: PLV performed at six different doses of perfluorodecalin in sequence (3, 6, 9, 12, 15, and 18 mL/kg every 15 min). MEASUREMENTS AND RESULTS: Our modified saline solution lavage induced atelectasis and hemorrhage confined to the dependent lung with severe hypoxia (PaO(2)/fraction of inspired oxygen = 37 +/- 6 mm Hg). Peak airway pressure (Ppeak) and inspiratory pause pressure (Ppause) with PLV were lower at doses of 3 to 15 mL/kg (all p < 0.05), but not different at a dose of 18 mL/kg, when compared with gas ventilation. Ppeak increased at doses of 12, 15, and 18 mL/kg, when each was compared with the preceding PFC dose. At increasing PFC doses, the change in the elastic component of airway pressure (Ppause after minus Ppause before) was negative until the dose of 9 mL/kg, but was positive at doses of 12 mL/kg and above. The change in the resistive component ([Ppeak minus Ppause] after minus [Ppeak minus Ppause] before) was negative until the dose of 6 mL/kg, but was positive at the dose > or = 9 mL/kg. CONCLUSION: Respiratory mechanics during PLV for dependent lung-dominant lung injury were optimal at a PFC dose less than the FRC.

Animals↗

PubMed2000

The value of interleukin-12 as an activity marker of pulmonary sarcoidosis.

BACKGROUND: Sarcoidosis is characterized by hyperactivity of T-helper lymphocytes and recent studies showed that they were mainly Th1 cells. IL-12 is a major cytokine inducing Th1 differentiation of naive T cells. This study was performed to test whether IL-12 can be a marker for disease activity and possibly a prognosis in sarcoidosis. METHODS: IL-12 levels of BALF (BALF-IL-12) and conditioned medium of alveolar macrophages (AM) were measured by ELISA in 36 patients with pulmonary sarcoidosis (14 males and 22 females, mean age: 39.6 +/- 11.0 years) and eleven normal controls. Clinically, 16 patients had active sarcoidosis and 20 had an inactive disease. RESULTS: BALF-IL-12 of sarcoidosis patients (41.3 +/- 43.9 pg/ml) was significantly higher than that of normal controls (2.5 +/- 0.4 pg/ml) (p < 0.001). The patients with active disease (71.3 +/- 54.3 pg/ml) had a higher BAL-IL-12 level than those with inactive disease (17.3 +/- 13.8 pg/ml) (p = 0.0001). It had a significant correlation with the number of T4 cells (p = 0.0001), total cell number, number and percentage of lymphocytes (p = 0.0001) and AM (p = 0.001) in BALF. It was also significantly correlated with soluble ICAM-1 levels in serum (p = 0.0001) and BALF (p = 0.002), and ICAM-1 expression of AM (p = 0.001). Furthermore the patients whose condition worsened without therapy had a significantly higher initial BALF-IL-12 level than the patients whose condition improved spontaneously. The AM of sarcoidosis secreted significantly more IL-12 (133 +/- 177 pg/ml) than AM of controls (68.3 +/- 43.7 pg/ml) (p = 0.038). CONCLUSION: Our data suggest that the BALF-IL-12 level can be used as a marker of the activity of pulmonary sarcoidosis and possibly prognosis.

Adult↗

PubMed1999

Isolation and characterization of a thermophilic lipase from bacillus thermoleovorans ID-1.

A thermophilic microorganism, Bacillus thermoleovorans ID-1, isolated from hot springs in Indonesia, showed extracellular lipase activity and high growth rates on lipid substrates at elevated temperatures. On olive oil (1.5%, w/v) as the sole carbon source, the isolate ID-1 grew very rapidly at 65 degrees C with its specific growth rate (2.50 h(-1)) and its lipase activity reached the maximum value of 520 U l(-1) during the late exponential phase and then decreased. In addition to this, isolate ID-1 could grow on a variety of lipid substrates such as oils (olive oil, soybean oil and mineral oil), triglycerides (triolein, tributyrin) and emulsifiers (Tween 20, 40). The excreted lipase of ID-1 was purified 223-fold to homogeneity by ammonium sulfate precipitation, DEAE-Sephacel ion-exchange chromatography and Sephacryl S-200 gel filtration chromatography. As a result, the relative molecular mass of the lipase was determined to be 34 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme showed optimal activity at 70-75 degrees C and pH 7.5 and exhibited 50% of its original activity after 1 h incubation at 60 degrees C and 30 min at 70 degrees C and its catalytic function was activated in the presence of Ca(2+) or Zn(2+).

Bacillus↗

PubMed1999

Discomfort caused by bonded lingual orthodontic appliances in adult patients as examined by retrospective questionnaire.

A retrospective questionnaire survey of 111 retention-period adult patients was performed to examine discomfort that may be caused by bonded lingual orthodontic appliances. Despite instructions to avoid or relieve the discomfort, 57% to 76% of patients complained of tongue soreness, difficulty in chewing fibrous food, difficulty in pronouncing the s and t sounds, and difficulty in tooth brushing after the bonding of lingual appliances; the levels were significantly higher than those undergoing edgewise labial treatment. Twenty percent to 44% of patients experienced high levels of the aforementioned discomfort. Although this discomfort decreased gradually with time, 20% to 46% of patients felt discomfort until after the removal of the lingual appliances. The ratio of tongue soreness and speech difficulty caused by upper lingual bracket application to lower lingual bracket application was almost equal. Rank correlation analyses revealed two things: the deeper the bite, the greater the level of tongue soreness, teeth pain and difficulty in chewing tough food; and the larger the overjet, the greater the level of tongue soreness.

Adult↗

PubMed1999

Respiratory and haemodynamic effects of the prone position at two different levels of PEEP in a canine acute lung injury model.

This study was designed to examine whether the oxygenation response in the prone position differs in magnitude depending on the level of positive end-expiratory pressure (PEEP) applied in the supine position, and whether cardiac output (CO) increases in the prone position. In seven supine dogs, acute lung injury was established by saline lavage (arterial oxygen tension (Pa,O2)/inspiratory oxygen fraction (FI,O2) 17.8+/-9.6 kPa (134+/-72 mmHg)), and inflection point (Pflex) of the respiratory system was measured (6.6+/-1.4 cmH2O). Pa,O2/FI,O2 and CO of the supine and prone positions were obtained under the application of low PEEP and then under optimal PEEP (2 cmH2O below and above Pflex, respectively). The net increase in Pa,O2/FI,O2 by prone positioning was greater at low PEEP (27.3+/-12.0 kPa (205+/-90 mmHg)) than at optimal PEEP (4.4+/-13.0 kPa (33+/-98 mmHg)) (p=0.006). CO decreased significantly with optimal PEEP in the supine position (2.4+/-0.5 versus 3.1+/-0.4 L x min(-1) at baseline, p<0.001), and increased to 3.4+/-0.6 and 3.6+/-0.7 L x min(-1) in the prone position at 5 min and 30 min, respectively (both p=0.018). When the dogs were turned supine at optimal PEEP, CO again decreased (2.4+/-0.5 L x min(-1), p<0.001). In conclusion, the prone position augmented the effect of relatively low positive end-expiratory pressure on oxygenation, and attenuated the haemodynamic impairment of relatively high positive end-expiratory pressure in a canine acute lung injury model.

Animals↗

PubMed1999

Heat shock response decreases endotoxin-induced acute lung injury in rats.

OBJECTIVE: Transient whole-body hyperthermia was reported to reduce lung damage in a rat with intra-abdominal sepsis produced by caecal perforation. METHODOLOGY: In order to determine the effect of heat shock response on acute lung injury induced by endotoxin, which plays a central role in the pathogenesis of sepsis, we instilled either saline or lipopolysaccharide (LPS) intravenously with and without heat pretreatment in rats. The heated rats had their rectal temperature raised to more than 40 degrees C for 13 min 18 h before intravenous administration of saline or LPS. RESULTS: We found that the lung leak was significantly increased among the rats given LPS intravenously with (median, 0.17; range, 0.15-0.22; n = 10) and without heat pretreatment (0.23; 0.17-0.30; n = 10) compared with those of saline-treated rats (0.13; 0.10-0.14; n = 10) (P < 0.05 in each). However, rats given LPS after heat pretreatment had significantly decreased lung leak index compared with those of LPS-treated rats without heat pretreatment (P < 0.05). Rats administered LPS intravenously showed increased myeloperoxidase activity without heat pretreatment (19.01; 9.34-28.00 U/g; n = 10) compared with that of saline-treated rats (7.09; 4.49-10.56 U/g; n = 5) (P < 0.05) (Fig. 2). Myeloperoxidase activity of the rats treated with LPS with heat pretreatment (5.57; 2.87-8.96 U/g; n = 10) was significantly decreased to the level of normal control compared with that of LPS-treated rats without heat pretreatment (P < 0.05). The levels of heat shock proteins (HSP72) in lung tissue, which were examined by western blot analysis, were increased over baseline levels at 23 h after hyperthermic stress. CONCLUSIONS: These observations show that brief heat shock response is associated with the induction of HSP72 protein synthesis and attenuated neutrophil recruitment and acute lung leak is induced by endotoxin in rats.

Acute Disease↗

PubMed1999

Drug resistance in lung cancer.

The major problem in lung cancer chemotherapy is the emergence of inherent and acquired drug resistance of the cancer cells. Establishment of drug-resistant sublines and comparative investigations of such cell lines with their parental cells to determine their molecular, biologic, and biochemical properties are important research strategies. Genetic changes in tumor cells may induce changes in their biochemical properties and chemosensitivity. Many mechanisms that render tumor cells resistant have been identified, and they have provided new molecular targets for surrogate markers to predict chemosensitivity. The new categories of anticancer drugs, such as topoisomerase I inhibitors and taxanes, and non-cytotoxic new drugs, have been introduced clinically. It is important to define the molecular determinants of resistance to these drugs. The development of an appropriate model for overcoming drug resistance is one of the important issues that should be solved before carrying out further clinical trials.

ATP Binding Cassette Transporter, Subfamily B, Mem↗