Biomedical subjects

M Younes

Publications and source records attributed to M Younes.

At least 55 records · Page 3Linked to original sources

PubMed1998

Control of breathing during sleep assessed by proportional assist ventilation.

We used proportional assist ventilation (PAV) to evaluate the sources of respiratory drive during sleep. PAV increases the slope of the relation between tidal volume (VT) and respiratory muscle pressure output (Pmus). We reasoned that if respiratory drive is dominated by chemical factors, progressive increase of PAV gain should result in only a small increase in VT because Pmus would be downregulated substantially as a result of small decreases in PCO2. In the presence of substantial nonchemical sources of drive [believed to be the case in rapid-eye-movement (REM) sleep] PAV should result in a substantial increase in minute ventilation and reduction in PCO2 as the output related to the chemically insensitive drive source is amplified severalfold. Twelve normal subjects underwent polysomnography while connected to a PAV ventilator. Continuous positive air pressure (5.2 +/- 2.0 cmH2O) was administered to stabilize the upper airway. PAV was increased in 2-min steps from 0 to 20, 40, 60, 80, and 90% of the subject's elastance and resistance. VT, respiratory rate, minute ventilation, and end-tidal CO2 pressure were measured at the different levels, and Pmus was calculated. Observations were obtained in stage 2 sleep (n = 12), slow-wave sleep (n = 11), and REM sleep (n = 7). In all cases, Pmus was substantially downregulated with increase in assist so that the increase in VT, although significant (P < 0.05), was small 0.08 liter at the highest assist). There was no difference in response between REM and non-REM sleep. We conclude that respiratory drive during sleep is dominated by chemical control and that there is no fundamental difference between REM and non-REM sleep in this regard. REM sleep appears to simply add bidirectional noise to what is basically a chemically controlled respiratory output.

Adult↗

PubMed1998

Susceptibility to periodic breathing with assisted ventilation during sleep in normal subjects.

Assisted ventilation with pressure support (PSV) or proportional assist (PAV) ventilation has the potential to produce periodic breathing (PB) during sleep. We hypothesized that PB will develop when PSV level exceeds the product of spontaneous tidal volume (VT) and elastance (VTsp . E) but that the actual level at which PB will develop [PSV(PB)] will be influenced by the DeltaPCO2 (difference between eupneic PCO2 and CO2 apneic threshold) and by DeltaRR [response of respiratory rate (RR) to PSV]. We also wished to determine the PAV level at which PB develops to assess inherent ventilatory stability in normal subjects. Twelve normal subjects underwent polysomnography while connected to a PSV/PAV ventilator prototype. Level of assist with either mode was increased in small steps (2-5 min each) until PB developed or the subject awakened. End-tidal PCO2, VT, RR, and airway pressure (Paw) were continuously monitored, and the pressure generated by respiratory muscle (Pmus) was calculated. The pressure amplification factor (PAF) at the highest PAV level was calculated from [(DeltaPaw + Pmus)/Pmus], where DeltaPaw is peak Paw - continuous positive airway pressure. PB with central apneas developed in 11 of 12 subjects on PSV. DeltaPCO2 ranged from 1.5 to 5.8 Torr. Changes in RR with PSV were small and bidirectional (+1.1 to -3.5 min-1). With use of stepwise regression, PSV(PB) was significantly correlated with VTsp (P = 0.001), E (P = 0.00009), DeltaPCO2 (P = 0.007), and DeltaRR (P = 0.006). The final regression model was as follows: PSV(PB) = 11.1 VTsp + 0.3E - 0.4 DeltaPCO2 - 0.34 DeltaRR - 3.4 (r = 0.98). PB developed in five subjects on PAV at amplification factors of 1.5-3.4. It failed to occur in seven subjects, despite PAF of up to 7.6. We conclude that 1) a PCO2 apneic threshold exists during sleep at 1.5-5.8 Torr below eupneic PCO2, 2) the development of PB during PSV is entirely predictable during sleep, and 3) the inherent susceptibility to PB varies considerably among normal subjects.

Adult↗

PubMed1998

Mechanisms by which COPD affects exercise tolerance.

In view of the recent advances in our understanding of the pathophysiology of COPD, we felt that it would be appropriate to examine the contribution of several abnormalities, not hitherto examined, to exercise limitation in this disease. These included: (1) The ability to exceed maximum expiratory flow (determined during forced maneuvers from TLC) during partial expiratory maneuvers. This is referred to as deltaFEV1. (2) Shape of the flow-volume curve (Shape). (3) Susceptibility to develop dynamic hyperinflation (dynamic hyperinflation index, DHI). (4) Ventilatory response to exercise (VEmax/VEpred). Twenty-four COPD patients (FEV1 = 42 +/- 13% pred) underwent symptom-limited progressive exercise. DeltaFEV1, shape, DHI and VEmax/VEpred were determined. All values were normalized to eliminate the effects of age, sex, and body size. Shape had no impact on peak VO2 (r = 0.8). DeltaFEV1 (r = 0.50), DHI (r = 0.50) and VEmax/VEpred (r = 0.46) correlated significantly with peak VO2 with all three exceeding FEV1 (r = 0.43). DHI and deltaFEV1 correlated significantly with each other (r = 0.43) suggesting that the latter exerts its beneficial effects by reducing the tendency to develop DH. We conclude that variability among patients in ventilatory response to exercise and in deltaFEV1 (likely an expression of extent of regional mechanical heterogeneity) contribute importantly to variability of exercise tolerance in COPD.

Aged↗

PubMed1998

Effects of pulmonary and intercostal denervation on the response of breathing frequency to varying inspiratory flow.

In mechanically ventilated awake and sleeping humans, it has been shown that increasing inspiratory flow rate (V'I) exerted a reflex excitatory effect on respiratory output. Mechanoreceptors located in intercostal muscles or within the lung have been suggested as possible pathways that may mediate the excitatory effect of V'I. To test this, five patients with bilateral lung transplantation (LTP) and eight quadriplegics with spinal cord transection at the level of C6-C7 (QP) were studied. Patients were connected to a volume cycle ventilator in the assist volume-control mode and V'I was randomly changed. V'I pattern was square and all breaths were patient-triggered. V'I values of 30, 60 and 90 L x min(-1) were studied. Each level of V'I was sustained for 15 breaths. Airway pressures, end-tidal partial pressure of carbon dioxide (PCO2), airflows and volumes were measured breath by breath. Thirty seven trials in LTP and sixty in QP, where V'I was randomly changed between 30 and 90 L x min(-1), were analysed. In both groups of patients, minute ventilation increased and total breath duration decreased significantly as V'I increased. These changes were complete in the first breath after V'I transition, without evidence of adaptation of the response. The magnitude of the response did not differ between the two groups of patients and was comparable to that observed previously in conscious normal subjects. We conclude that the excitatory effect of inspiratory flow rate on breathing frequency persists in patients who have pulmonary or intercostal denervation. These results do not favour receptors located within the lung (below the resection lines) or in the intercostal muscles to mediate the response of breathing frequency to flow rate.

Denervation↗

PubMed1998

13th meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): alternative testing methodologies and conceptual issues.

Substantial world-wide resources are being committed to develop improved toxicological testing methods that will contribute to better protection of human health and the environment. The development of new methods is intrinsically driven by new knowledge emanating from fundamental research in toxicology, carcinogenesis, molecular biology, biochemistry, computer sciences, and a host of other disciplines. Critical evaluations and strong scientific consensus are essential to facilitate adoption of alternative methods for use in the safety assessment of drugs, chemicals, and other environmental factors. Recommendations to hasten the development of new alternative methods included increasing emphasis on the development of mechanism-based methods, increasing fundamental toxicological research, increasing training on the use of alternative methods, integrating accepted alternative methods into toxicity assessment, internationally harmonizating chemical toxicity classification schemes, and increasing international cooperation to develop, validate, and gain acceptance of alternative methods.

Animal Testing Alternatives↗

PubMed1998

Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife.

An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and dioxinlike polychlorinated biphenyls (PCBs) for both human, fish, and wildlife risk assessment. Based on existing literature data, TEFs were (re)evaluated and either revised (mammals) or established (fish and birds). A few mammalian WHO-TEFs were revised, including 1,2,3,7,8-pentachlorinated DD, octachlorinated DD, octachlorinated DF, and PCB 77. These mammalian TEFs are also considered applicable for humans and wild mammalian species. Furthermore, it was concluded that there was insufficient in vivo evidence to continue the use of TEFs for some di-ortho PCBs, as suggested earlier by Ahlborg et al. [Chemosphere 28:1049-1067 (1994)]. In addition, TEFs for fish and birds were determined. The WHO working group attempted to harmonize TEFs across different taxa to the extent possible. However, total synchronization of TEFs was not feasible, as there were orders of a magnitude difference in TEFs between taxa for some compounds. In this respect, the absent or very low response of fish to mono-ortho PCBs is most noticeable compared to mammals and birds. Uncertainties that could compromise the TEF concept were also reviewed, including nonadditive interactions, differences in shape of the dose-response curve, and species responsiveness. In spite of these uncertainties, it was concluded that the TEF concept is still the most plausible and feasible approach for risk assessment of halogenated aromatic hydrocarbons with dioxinlike properties.

Animals↗

PubMed1997

Reevaluation of cyclosporine induced hepatotoxicity in the isolated perfused rat liver.

UNLABELLED: Livers of male rats were perfused for 120 min in a recirculating hemoglobin-free system with different concentrations of cyclosporine (CS 2, 10, 50, 150 and 200 mg/l). CS produced damage to the livers in a dose dependent manner. The first sign of hepatotoxicity was a reduction of bile flow amounting to 50% already at 50 mg/l CS. At concentrations of 150 mg/l and 200 mg/l, CS lead to a nearly complete suppression of bile flow, furthermore to a release of cytosolic (GPT, glutamate-pyruvate transaminase, LDH, lactate dehydrogenase) and mitochondrial (GLDH, glutamate dehydrogenase) enzymes into the perfusate and to a decrease in hepatic oxygen consumption (30% at 200 mg/l CS). As a consequence of the reduced aerobic energy supply, hepatic ATP concentration declined (70% at 200 mg/l CS). The hepatic concentrations of reduced glutathione (GSH) were not changed but those of oxidized glutathione (GSSG) increased up to 5-fold by CS. Malondialdehyde (MDA) concentrations in the liver and in the perfusate were not affected consistently by CS. The toxic actions of CS in the isolated rat liver were not influenced (a) by the feeding status of the rats (fed or fasted before surgery) or (b) by addition of superoxide dismutase (SOD, 20 mg/l) and catalase (20 mg/l) to the perfusate 30 min before CS. On the other hand, CS-induced hepatic injury could be attenuated or inhibited completely by addition to the perfusate of (1) 2 mmol/l GSH; (2) 12 mmol/l serine; (3) 12 mmol/l glycine; (4) 0.09 mmol/l deferoxamine (DFO). CONCLUSIONS: CS induces cholestasis at lower concentrations, probably by another mechanism(s) than the other signs of hepatotoxicity (enzyme release, ATP depletion). Several lines of evidence indicate a probable participation of reactive oxygen species in CS-induced hepatotoxicity. GSH, DFO, glycine and serine could provide therapeutic opportunities to prevent CS-induced hepatotoxicity in patients treated with high doses of CS.

Alanine Transaminase↗

PubMed1997

Overexpression of Glut1 and Glut3 in stage I nonsmall cell lung carcinoma is associated with poor survival.

BACKGROUND: Increased expression of Glut1 and Glut3 has been reported in many human cancers, including nonsmall cell lung carcinoma (NSCLC). The aim of this study was to determine the biologic significance of Glut1 and Glut3 overexpression in Stage I NSCLC. METHODS: Using immunohistochemistry and polyclonal anti-Glut1 and anti-Glut3 antibodies, the authors immunostained sections of formalin fixed, paraffin embedded tissues from 289 Stage I NSCLCs. The Kaplan-Meier survival method, the log rank test, and Fisher's exact test were used for statistical analysis. RESULTS: Of the 289 cases, 49 (17%) were negative for both Glut1 and Glut3, 239 (83%) were Glut1 positive, 61 (21%) were Glut3 positive, 179 (62%) were positive for Glut1 but negative for Glut3, 1 (0.3%) was positive for Glut3 but negative for Glut1, and 60 (21%) were positive for both Glut1 and Glut3. Only 1 of 50 Glut1 negative tumors (2%) was positive for Glut3, whereas 60 of 239 Glut1 positive tumors (25%) were positive for Glut3 (P < 0.0001). Glut1 or Glut3 were detected more often in poorly differentiated and undifferentiated tumors (P < 0.0001 and P = 0.0008, respectively). Overexpression of Glut1 and/or Glut3 was associated with poorer survival (P = 0.0133), especially in patients with well-differentiated and moderately differentiated tumors (P = 0.0017). CONCLUSIONS: In Stage I NSCLC, Glut3 overexpression likely occurs after Glut1 overexpression. The appearance of Glut1 positive clones is associated with aggressive biologic behavior, which is worsened by the emergence of Glut3 positive clones. Glut1 and Glut3 are significant of poor prognosis indicators in cases of NSCLC.

Adult↗

PubMed1997

Absence of prognostic significance of bcl-2 immunopositivity in non-small cell lung cancer: analysis of 427 cases.

The bcl-2 gene product inhibits apoptosis and is thought to participate in oncogenesis. Association of bcl-2 immunopositivity with improved prognosis of non-small cell lung cancers (NSCLC) is controversial. Although two studies have reported better survival in bcl-2-immunopositive NSCLCs, a third series has contradicted this finding. The authors studied a relatively larger case series involving 427 patients for whom detailed information on long-term follow-up was available to determine the prognostic significance of bcl-2 expression. The study included 252 adenocarcinomas (AC), 111 squamous cell carcinomas (SCC), and 64 large cell carcinomas (LC). After antigen retrieval, sections were immunostained using a monoclonal anti-bcl-2 antibody (1:60, Clone 124, Dako) and the avidin-biotin complex technique. Staining was scored as positive or negative and also on a semiquantitative scale as 0, low (<10%), moderate (10% to 75%), or extensive (>75%). Bcl-2 immunoreactivity was correlated with survival using the actuarial survival method, Kaplan-Meier method, and log-rank test and was not associated with statistically significant differences in survival for NSCLCs (P = .5537). Differences in survival remained insignificant even after NSCLCs were stratified for cell type, stage, or grade, singly or in combination. Therefore, using this method, bcl-2 immunopositivity does not appear to act as an independent prognostic indicator in NSCLCs.

Adenocarcinoma↗

PubMed1997

Expression of the human erythrocyte glucose transporter Glut1 in cutaneous neoplasia.

BACKGROUND: The increased glucose uptake seen in cancer cells correlates with the expression of human erythrocyte glucose transporter (Glut1) protein in certain human malignancies. OBJECTIVE: Our purpose was to determine Glut1 expression in cutaneous neoplasms. METHODS: A polyclonal anti-Glut1 antibody (MYM) and a standard ABC immunoperoxidase technique were used to determine Glut1 expression in invasive squamous cell carcinomas (SCCs), SCC in situ, basal cell carcinomas (BCCs), melanomas, actinic keratoses (AKs), seborrheic keratoses, common acquired nevi, and scars with regenerative epidermal hyperplasia. RESULTS: All of the cases of SCC in situ, 14 of 15 (93%) of the SCC, and 13 of 15 AKs (87%) showed intense membranous staining for Glut1. Glut1 staining was present in the epidermis of 8 of 15 scars (53%) but was not detected in any BCC, even in areas of focal keratinization and squamous metaplasia. Glut1 reactivity was absent in the melanomas and seborrheic keratoses. CONCLUSION: Glut1 expression in a cutaneous lesion strongly suggests a proliferative lesion of the squamous cell type.

Antibodies↗

PubMed1997

p53 Protein accumulation is a specific marker of malignant potential in Barrett's metaplasia.

Our aim was to determine the sensitivity and specificity of p53 accumulation as a marker of malignant potential in Barrett's metaplasia (BM). One hundred eighty biopsies from 61 patients with BM were evaluated for p53 accumulation by immunohistochemistry. Of 25 patients with LGD, 9 had p53-positive biopsies, and of these 5 (56%) developed HGD/CA, whereas 16 had p53-negative biopsies and none (0%) developed HGD/CA after similar follow-up times (P = 0.0108). As a marker of malignant potential in BM, p53 accumulation has a sensitivity of 100%, specificity of 93%, and a predictive value of a positive test of 0.56, compared to sensitivity of 100%, specificity of 64%, and predictive value of a positive test of 0.2 for a histologic diagnosis of LGD. We conclude that: (1) p53 accumulation is more specific and has better predictive value for subsequent development of HGD/CA than histologic diagnosis of LGD. (2) Patients with LGD and p53-positive biopsies are more likely to develop HGD/CA; therefore, they should be followed up more closely than those with LGD and p53-negative biopsies.

Barrett Esophagus↗

PubMed1997

Analysis of p53 gene deletions in patients with non-Hodgkin's lymphoma by dual-colour fluorescence in-situ hybridization.

The most common tumour suppressor gene altered in human cancers is p53, which is located on the short arm of chromosome 17. Structural abnormalities of the short arm and loss of chromosome 17 have been reported to confer resistance to chemotherapy in patients with non-Hodgkin's lymphoma (NHL). Therefore we studied the incidence and prognostic value of p53 deletions in patients with NHL by fluorescence in-situ hybridization using a 40 kb cosmid probe. Specimens obtained from 79 patients with NHL were studied. 46 patients were untreated, and 33 were previously treated. 40 tumours had indolent and 39 had aggressive histologies. p53 deletions were observed in 14 specimens (18%) in 32-90% of the cells. No statistically significant difference in the incidence of p53 deletion was observed between indolent and aggressive NHLs or between untreated and previously treated patients. However, p53 deletions were observed in three of four patients with transformed lymphoma. In the untreated patients, p53 deletion had no effect on response to therapy, time to treatment failure, or survival. We conclude that p53 deletions are uncommon in NHL, and may be frequent in patients with transformed lymphoma. In this study, p53 deletions did not influence treatment outcome or prognosis of NHL. Because monosomy 17 and 17p abnormalities have been reported to confer poor prognosis in NHL, other tumour suppressor genes on 17p should therefore be studied.

Aneuploidy↗

PubMed1997

Effects of inspiratory muscle unloading on the response of respiratory motor output to CO2.

Inspiratory muscle output is downregulated when the mechanical load is reduced in awake humans. It is not known whether this is related to reduction in PCO2 or to removal of load-related neural responses. To address this issue, we did Read CO2 rebreathing tests in 13 normal subjects with and without unloading and compared respiratory output at identical end-tidal PCO2 (PET(CO2)) levels. Unloading was carried out with proportional assist ventilation (flow assist = 2 cm H2O/L/s plus volume assist = 4 cm H2O/L, representing approximately 50% reduction of the normal resistance and elastance). Ventilatory output (n = 13), total pressure of respiratory muscles (Pmus, n = 8), and transdiaphragmatic pressure (Pdi, n = 5) were computed at different PET(CO2) levels. Pmus was computed from esophageal pressure (Pes) using the Campbell diagram, and Pdi was measured from the difference between gastric pressure and Pes. Unloading caused an increase in ventilation (VI) and tidal volume (VT) at all PET(CO2) levels with no significant effect on slope (VI/PET(CO2) or VT/PET(CO2)) or respiratory rate. At low PET(CO2) (50 mm Hg), Pdi and Pmus waveforms did not differ with and without unloading. At high PET(C02) (59 mm Hg), peak Pdi and Pmus decreased by only 18.8 +/- 8.3% and 13.8 +/- 9.5%, respectively (NS, p > 0.05). Using a model that allows nonlinearity in the pressure-volume relation and for intrinsic muscle properties (force-length and force-velocity relations), we estimated the expected changes in mean VT and VI when the level of assist used in this study was applied in the absence of any change in neural output response to CO2. The predicted and observed changes in VT and VI were similar. We conclude that when chemical stimuli are rigorously controlled, unloading does not result in downregulation of respiratory muscle activation.

Adult↗

PubMed1997

Respiratory response to CO2 during pressure-support ventilation in conscious normal humans.

The respiratory response to CO2 during pressure-support ventilation (PSV) was studied in 16 conscious normal humans. The subjects breathed through a mouthpiece connected to a ventilator in PSV mode, with pressure set to the highest comfortable level for each subject (10.1 +/- 0.6 cm H2O, mean +/- SE). Compared with breathing spontaneously through the ventilator (CPAP mode with zero positive end-expiratory pressure), with PSV, tidal volume (VT) increased significantly (1.16 +/- 0.1 versus 0.85 +/- 0.04 L), whereas breathing frequency (f) remained stable (16.0 +/- 0.9 versus 15.6 +/- 1.1 breaths/min). As a result, the subjects hyperventilated, decreasing significantly end-tidal PCO2 (PETCO2, 23.5 +/- 1.2 versus 35.5 +/- 1.1 mm Hg). Fraction of inspired CO2 (FICO2) was then increased in steps, and changes in respiratory motor output were quantitated from changes in f, VT, ventilation (VI), peak inspiratory flow (Vpeak), and muscle pressure (Pmus). Pmus was calculated by the equation of motion, based on respiratory system mechanics, which were measured previously by airway occlusion at end-inspiration, VT, VI, and Pmus increased significantly with increasing PETCO2, and the response was detectable even below eupneic levels; f remained relatively stable over a wide range of PETCO2 (23 to 45 mm Hg) and increase significantly only when PETCO2 approached 50 mm Hg. These results indicate that in conscious normal humans during PSV, CO2 responsiveness extends well into hypocapnia and is expressed principally as an increase in intensity of respiratory motor output with little change in respiratory rate.

Adult↗

PubMed1997

Effect of inspiratory flow rate on respiratory rate in intubated ventilated patients.

It has previously been demonstrated that in normal subjects using a volume-cycled ventilator, increasing inspiratory flow rate increases respiratory rate. We undertook the current study to determine (1) whether this effect is also present in patients with respiratory disease and (2) whether the effect is independent of upper airway receptors. Eight ventilator-dependent patients in the intensive care unit were studied. Patients were ventilated in the assist-control mode with the back-up rate set at 0.5 breaths/min to ensure that all breaths were patient-triggered. While tidal volume was held constant, flow was changed from a baseline flow of 60 L/min. Trials involved changing flow to either 30 or 90 L/min. There was a significant decrease in respiratory rate (-3.4 +/- 0.6 min-1, p < 0.001) when flow was decreased from 60 to 30 L/min. There was a significant increase in respiratory rate (2.3 +/- 0.8 min-1, p < 0.05) when flow was increased from 60 to 90 L/min. As a result of the change in respiratory rate, TE (expiratory time) showed a variable response to changes in flow rate, with some patients actually demonstrating a reduced TE with higher flow rates. No patients experienced the increase in TE that would have been predicted without a change in respiratory rate. We conclude that in intubated ventilated patients, spontaneous respiratory rate is sensitive to inspiratory flow rate. This effect appears to be independent of upper airway receptors, since it was observed with a by-passed upper airway. The increase in respiratory rate seen at higher flow rates undermines attempts to increase TE by increasing flow rates. It may also cause a tendency toward respiratory alkalosis.

Adolescent↗

PubMed1997

High c-erbB-3 protein expression is associated with shorter survival in advanced non-small cell lung carcinomas.

c-erbB-3 is a new member of the Type I growth factor receptor family that includes epidermal growth-factor receptor (also called c-erbB-1) and HER-2/neu (also called c-erbB-2). Frequency and significance of c-erbB-3 overexpression in lung cancers have not been reported previously. A series of 549 cases of primary lung carcinomas were immunostained with a monoclonal anti-human c-erbB-3 antibody (Clone RTJ.1) using formalin-fixed, paraffin-embedded archival tissue. Sharp membranous staining or punctate cytoplasmic staining was interpreted as positive and scored 0 (< 5% of tumor cells), 1 (5-9%), 2 (10-49%), or 3 (> or = 50%). Medical records were reviewed for clinical data, including stage and survival. Actuarial cumulative survival analysis with the Mantel-Cox test was performed on 443 cases that had a single primary site in the lung of pure non-small cell carcinoma (adenocarcinoma, squamous cell carcinoma, large cell carcinoma) and that also had follow-up data for more than 3 months. In all stages, squamous cell carcinoma showed the greatest rate of high c-erbB-3 positivity (score, 3) (34/119; 28.6%), followed by adenocarcinoma (41/256; 15.9%) and large cell carcinoma (7/66; 10.6%). Patients with high c-erbB-3 expression (score, 3) survived for significantly shorter times than did patients with low c-erbB-3-expression (score, 0-2) in Stages III and IV (P = 0.002), but not in Stage I or II non-small cell lung carcinomas. In conclusion, high c-erbB-3 expression in advanced non-small cell lung carcinomas might be an adverse prognostic factor. This finding suggests that c-erbB-3 might be a potential target for molecular therapy in advanced non-small cell lung carcinomas.

Adenocarcinoma↗

PubMed1997

Human erythrocyte glucose transporter (Glut1) is immunohistochemically detected as a late event during malignant progression in Barrett's metaplasia.

We have previously demonstrated that the human erythrocyte glucose transporter (Glut1) is expressed in adenocarcinoma arising in Barrett's metaplasia (BM). We have also shown that Glut1 is expressed as a late event during colorectal carcinogenesis. The aim of this work was to determine the chronology of Glut1 expression during the neoplastic progression in Barrett's metaplasia. Formalin-fixed, paraffin-embedded tissue sections of 251 biopsies from 97 patients with BM were immunostained with the anti-Glut1 antibody MYM, after microwave-aided antigen retrieval, using the standard avidin-biotin complex immunoperoxidase technique. Dysplasia was graded as negative (ND), low grade (LGD)/indefinite or high grade (HGD). None of the 181 biopsies with ND (0%) or 51 biopsies with LGD (0%) showed Glut1 immunoreactivity. More importantly, although 0 of 6 biopsies with HGD (0%) expressed Glut1, 9 of 13 biopsies with adenocarcinoma (69%) were Glut1 positive (P = 0.0108, Fisher's exact test). Our results indicate that Glut1 is expressed as a late event during the neoplastic progression in BM. Prospective studies are needed to determine the clinical utility of Glut1 immunoreactivity as a marker of carcinoma in patients with BM.

Adenocarcinoma↗

PubMed1997

Protection by glycine against hypoxia-reoxygenation induced hepatic injury.

Isolated perfused livers from rats fasted 16 h before surgery showed a strong decrease in oxygen consumption as well as hepatotoxic responses when subjected to 30 min of hypoxia (95%, N2/5% CO2) followed by 90 min of reoxygenation (95% O2/5% CO2). Toxicity was evident by a release of enzymes (LDH, GPT, GLDH) into the perfusate and by a nearly complete suppression of bile flow. Hepatic reduced gluthathione dropped to about 20% and hepatic ATP to about 50% of the initial values. Furthermore, the concentrations of thiobarbituric acid reactive (TBA) material increased eightfold in the perfusate and by 70% of the control values in the livers. Glycine added to the perfusate at concentrations of 3, 6 and 12 mmol/l prevented dose-dependently all measures of hepatotoxicity as well as the indices of lipid peroxidation induced by hypoxia/reoxygenation. A maximal and nearly complete protection was obtained with 12 mmol/l glycine. Glycine increased the bile flow of perfused livers not subjected to hypoxia and attenuated the drop of bile flow induced by hypoxia-reoxygenation. Ligation of the bile duct, however, did not influence the cytoprotective effects of glycine in hypoxia-reoxygenation induced hepatic injury. In conclusion, glycine is an effective antidote against hypoxia-regoxygenation induced injury of the isolated rat liver.

Alanine Transaminase↗