Biomedical subjects

J J Sánchez

Publications and source records attributed to J J Sánchez.

At least 19 recordsLinked to original sources

PubMed2005

Biweekly regimen of cisplatin, gemcitabine and vinorelbine for advanced non-small-cell lung cancer.

PURPOSE: Improving chemotherapeutic efficacy in non-small cell lung cancer (NSCLC) will require the development of new strategies to better use currently available agents. To assess the efficacy and safety of a biweekly regimen of cisplatin, gemcitabine and vinorelbine for advanced non-small-cell lung cancer. METHODS: Patients with selected stage IIIb (pleural effusion)/stage IV NSCLC, performance status of 0-2 and normal organ function were eligible. Treatment consisted of cisplatin 100 mg/m(2) on day 1 plus gemcitabine, 1,000 mg/m(2) and vinorelbine 25 mg/m(2) on days 1 and 15 every 28 days. RESULTS: Of the 40 patients enrolled and assessable for response, there were five (12.5%) with confirmed complete response and 14 (35%) with a confirmed partial response for an overall response rate of 47.5%. Nine patients had stable disease while 12 (30%) progressed. Median progression-free survival and overall survival for all patients were 6.3 and 11.1 months, respectively. Toxicity was principally hematologic, with grade 3-4 neutropenia in 30%, and grade 3-4 nausea/vomiting in 22.5%. There were no treatment-related deaths. CONCLUSIONS: The biweekly regimen of cisplatin, gemcitabine and vinorelbine is associated with a high rate of response, lesser toxicity than other three-drug regimens and no benefit of survival. Therefore, the regimen under study may be an appealing alternative when considering other treatment modalities for advanced lung cancer, such as neoadjuvant therapy.

Adult↗

PubMed2005

Breast cancer prognosis determined by gene expression profiling: a quantitative reverse transcriptase polymerase chain reaction study.

PURPOSE: We sought to reproduce with quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) the results obtained with a 70-gene expression profile that has been described previously in breast cancer. PATIENTS AND METHODS: Frozen breast cancer samples from patients who were operated on were used to isolate tumor RNA. Ninety-six patients with stage I to II disease were included. Median age was 57 years (range, 27 to 80 years). Forty-eight patients had lymph node-negative and 48 lymph node-positive disease. qRT-PCR amplifications were performed and the results were correlated with clinical data. RESULTS: After a minimum follow-up of 5 years, 25 patients had a relapse. The gene profile divided patients into two groups with poor and good prognosis. Significant differences with regard to grade of differentiation, size and hormone receptors were seen between the two groups. The gene profile was significantly associated with relapse-free survival and overall survival in the whole group of 96 patients. Multivariate analysis showed that only lymph node status and gene profile were significantly correlated to overall survival. CONCLUSION: qRT-PCR reproduced the results obtained with microarrays for a prognostic gene profile in women with early-stage breast cancer.

Adult↗

PubMed2005

[Monitoring hemodialysis dose with ionic dialisance in on-line hemodiafiltration].

Until now, with the ionic dialysance measurement, it has been possible to determine hemodialysis dose in each session of hemodialysis (HD) and in the conventional hemofiltration (HDF) but not in the modality of on-line HDF. Recently it is possible with a new biosensor that allows to measure the dose in on-line HDF. The aim of this study was to evaluate the value of this biosensor in different dialysis situations comparing the dialysis dose measured in blood in comparison with the values obtained from the sensor. We have analysed 192 hemodialysis sessions performed in 24 patients, 15 male and 9 female, mean age of 70.2 +/- 12 years, included in on-line HDF. All treatments were done using 4008H (Fresenius) monitor equipped with on-line clearance monitoring (OCM), that measure, with non invasive monitoring, the effective ionic dialysance equivalent to urea clearance. Every patient received eight dialysis sessions: one with dialysate flow (Qd) 500 ml/min, two with HD and Qd 800 ml/min and five with on-line HDF. Other habitual haemodialysis parameters were no changed, dialysis time 200 +/- 63 min (135-300) and blood flow 421 +/- 29 ml/min (350-450). Initial and final ionic dialysance values (K), final Kt, Kt/V measured with OCM using V of Watson, and Kt/V determined in blood pre and postdialysis concentrations of urea (Daugirdas second generation), were measured. The mean of initial K was 251 +/- 21 ml/min and the final K was 234 +/- 24 ml/min. The Kt measured with OCM was 50.6 +/- 17 L, 51.2 +/- 17 in men and 49.7 +/- 16 in women. The V (Watson) was 34.5 +/- 6 L. The Kt/V measured with the Kt of OCM and V was 1,499 +/- 0.54 and Kt/V measured in blood samples was 1,742 +/- 0.58. The correlation between both values was 0.956. The Kt was different according to dialysis modality used: in HD and Qd 500 was 44.7 +/- 15 L, in HD and Qd 800 was 50.7 +/- 17 and in on-line HDF (22.1 +/- 7 L of reposition volume), was 51.8 +/- 17 L. The Kt/V from blood samples also shows variation: in HD and QD 500 was 1.60 +/- 0.55, in HD and Qd 800 was 1,726 +/- 0.56 and in on-line HDF was 1,776 +/- 0.59. In this study has been observed a close correlation between the new biosensor OCM with the measures obtained from the blood samples. For this reason this sensor it is useful in all modalities of dialysis treatment, included on-line HDF. The sensor was able to discriminate the efficacy of different dialysis modalities used in this study.

Adult↗

PubMed2004

Irinotecan plus raltitrexed as first-line treatment in advanced colorectal cancer: a phase II study.

To evaluate the efficacy and toxicity of irinotecan (CPT-11) in combination with raltitrexed as first-line treatment of advanced colorectal cancer (CRC). A total of 91 previously untreated patients with advanced CRC and measurable disease were enrolled in this phase II study. The median age was 62 years (range 31-77); male/female 54/37; ECOG performance status was 0 in 50 patients (55%), one in 39 (43%) and two in two (2%). Treatment consisted of CPT-11 350 mg x m(-2) in a 30-min intravenous infusion on day 1, followed after 30 min by a 15-min infusion of raltitrexed 3 mg x m(-2). Measurements of efficacy included the following: response rate, time to disease progression and overall survival. Of the 83 evaluable patients valuable to objective response, there were five complete responses (6%) and 23 partial responses (28%), for an overall response rate of 34% (95% CI: 25.9-46.5%). In all, 36 patients (43%) had stable disease, whereas 19 (23%) had a progression. The median time to progression was 11.1 months and the median overall survival was 15.6 months. A total of 487 cycles of chemotherapy were delivered with a median of five per patient. Grade 3-4 WHO toxicities were as follows: diarrhoea in 13 patients (15%), nausea/vomiting in four (4%), transaminase increase in six (7%), stomatitis in two (2%), febrile neutropenia in three (3%), anaemia in five (6%) and asthenia in three (3%). The combination CPT-11-raltitrexed is an effective, well-tolerated and convenient regimen as front-line treatment of advanced CRC.

Adult↗

PubMed2004

[Improvement of nutritional status in patients with short daily on-line hemodiafiltration].

Daily dialysis have showed excellent results because a higher frequency of dialysis is more physiological and it decreases the fluctuation of liquid, solutes and electrolytes. Improvement of certain causes of anorexia such as postdialysis fatigue, reduction in fluid overload, uremic milieu, medium and large-sized molecule removal could be observed with daily dialysis. The aim of this study was to evaluate nutritional parameters when thrice weekly on-line hemodiafiltration (OL-HDF) were switched to daily OL-HDF. 24 patients have been studied. Eight patients, 6 males and 2 females, mean age of 65.9 +/- 14 years, on thrice weekly 4 to 5 hours OL-HDF were switched to 2 to 2.5 hours six times per week. Dialysis parameters were the same in both periods and only frequency and dialysis time were changed. Other sixteen patients, mean age of 68.4 +/- 14 years, were a control group which dialysis parameters were maintained. Clinical and biochemical outcome were carried out over twelve months. Daily OL-HDF group: Dry weight increased from 67.8 +/- 8 kg at baseline to 68.5 +/- 8 kg after three months, 69.3 +/- 8 kg after six months (NS), 69.5 +/- 8 kg after nine months (p < 0.05) and 70.8 +/- 8 (p < 0.01) after one year. Mean nPCR increased from 0.93 +/- 0.2 g/kg/d on baseline to 1.18 +/- 0.3 after three moths (P < 0.0-5), 1.13 +/- 0.2 after six months (NS), 1.06 +/- 0.2 after nine months (NS) and 1.10 +/- 0.2 after twelve months (NS). There were no significant changes in serum protein, albumin, prealbumin, transferrin, total cholesterol, HDL-c, LDL-c and triglycerides (TG). There were no changes in control group. Mean dry weight was 62.3 +/- 9 kg at baseline and 62.1 +/- 10 kg after one year. Mean nPCR was 0.97 +/- 0.2 g/kg/d on baseline and 1.03 +/- 0.2 g/kg/d after one year. Neither there were changes in serum protein, albumin, transferrin, total cholesterol, HDL-c, LDL-c and TG. Improvement in nutrition status has been observed with the change from thrice weekly OL-HDF to short daily OL-HDF. Increased appetite and protein intake was accompanied by a dry body weight increase of three kg after twelve months.

Adult↗

PubMed2003

Temperature-activity relationship for the intestinal Na+-K+-ATPase of Sparus aurata. A role for the phospholipid microenvironment?

The temperature dependence for Na(+)-K(+)-ATPase has been examined in the proximal-distal axis of the intestine of gilthead seabream (Sparus aurata), i.e. pyloric caeca (PC), anterior intestine (AI) and posterior intestine (PI). Data derived from the Arrhenius plots showed differences in terms of temperature discontinuity points ( Td) (13.29 degrees C, 16.39 degrees C and 17.48 degrees C for PC, AI and PI, respectively) and activation energy ratios (Ea(2)/Ea(1)) obtained at both sides of Td (2.38, 1.98 and 1.78, for PC, AI and PI, respectively). The analyses of polar lipids showed differences in the levels of certain fatty acids among intestinal regions. The content of each fatty acid and different fatty acid ratios were correlated with the corresponding Td and Ea(2)/Ea(1) values. Regression analyses revealed the existence of strong negative correlations between docosahexaenoic acid (22:6n-3, DHA) or the DHA/monoenes ratio and Td. No obvious relationships were observed for other polyunsaturated fatty acids (PUFA) nor saturated fatty acids. The results obtained in the present study indicate that the heterogeneous values of Td displayed by the Na(+)-K(+)-ATPase along the intestinal tract could be related to a modulatory role of certain fatty acid within the lipid microenvironment of the enzyme.

Animals↗

PubMed2003

New insights in beta-tubulin sequence analysis in non-small cell lung cancer.

Scarce data are available regarding the molecular mechanisms implicated in paclitaxel resistance. There is controversial data about beta-tubulin mutations role in paclitaxel resistance. We have conducted this trial to address the influence of beta-tubulin mutations in paclitaxel resistance in advanced non-small cell lung cancer (NSCLC). A group of 15 patients were biopsied and diagnosed of stages IIIB and IV NSCLC. Tumor specimens were used for DNA isolation and exon 4 of HM40 beta-tubulin isotype was amplified and automatically sequenced, using both intronic and exonic primers. Next, the chemotherapy schedule consisted of weekly paclitaxel (100 or 150 mg/m(2) x 6) followed 2 weeks later by cisplatin 100 mg/m(2) on day 1, gemcitabine 1000 mg/m(2) on days 1 and 14, and vinorelbine 25 mg/m(2) on days 1 and 14, every 28 days. Using exonic primers, gene sequence alterations were found in 13/15 (87%) patients, including transitions (codons 180 and 182) and one silent transversion (codon 195). Also, three transversions (codons 231, 234, and 235) were found in all patients and controls. All alterations disappeared when sequenced with intronic primers. Our results suggest that point mutations demonstrated with exonic primers but not with intronic ones are probably due to beta-tubulin pseudogenes present in advanced NSCLC specimens. Even so, when these beta-tubulin pseudogenes are found there is a clear relation with clinical response. Although these changes could be relevant in paclitaxel resistance, this observation must be proven in future clinical trials to resolve "the tubulin dilemma".

Adenocarcinoma↗

PubMed2003

[Effect of arterial pressure and age on renal function, The "Care for the Kidney" study].

BACKGROUND: The kidney is one of the principal target organs of hypertension. The mechanism by which hypertension damages the kidney and the relative contribution of high blood pressure to the progression of renal failure remains incompletely defined. The clinical quantification of renal function is usually thought to require determination of plasma clearance of endogenous creatinine (ClCr), an impractical test for epidemiological evaluation. For this reason several formulae have been proposed to estimate the ClCr from the serum creatinine concentration, such as sex, age, and body weight. The most often used formula is the one proposed by Crockroft and Gault in 1976. OBJECTIVE: To determine the prevalence of loss of renal function and the influence of hypertension and age on this loss in hypertensive and normotensive patients. PATIENTS AND METHOD: An observational, cross-sectional comparative study was carried out. 3,420 patients (1,171 normotensive and 2,249 hypertensive) were studied. Average age was 70 years (19.4% of patients < 65 years; 23.3% > 75 years). 98.1 of hypertensive patients were treated with drugs, 26.7% of them with more than one drug. 27.9% of treated patients achieved blood pressure control (< 140-90 mm Hg). The level of renal function was estimated by means of ClCr using the Crockroft and Gault formula. RESULTS: 3.9% of normotensive and 12.2% of hypertensive patients had serum creatinine values > 1.3 mg/dl, but 28.6% of normotensive and 40.4% of hypertensive had ClCr < 60 ml/min. The patients over 75 years had ClCr mean values < 60 ml/min. There was correlation between ClCr and age, but there was no correlation between ClCr and blood pressure values. CONCLUSIONS: The estimated ClCr decrease with age and there existed correlation between both variables. The ClCr is lower in hypertensive than in normotensive patients. Hypertension and age influence loss of renal function, but age is a determining factor. The estimated ClCr was a more sensible method of evaluating the loss of renal function than the serum creatinine values. The use of Crockroft and Gault formula can be useful for making diagnostic and therapeutic decisions in primary care.

Aged↗

PubMed2002

Raltitrexed in the treatment of elderly patients with advanced colorectal cancer: an active and low toxicity regimen.

In spite of the high prevalence of advanced colorectal cancer in the elderly, we have little data on the efficacy and toxicity of chemotherapy in this age group. Raltitrexed is a thymidylate synthetase inhibitor with known activity in the treatment of advanced colorectal cancer. The objective of this study was to analyse the efficacy and tolerance of raltitrexed in elderly patients with advanced colorectal cancer. 92 patients diagnosed with advanced colorectal cancer aged >or=70 years were entered into the study. Raltitrexed was given at a dose of 3 mg/m(2) once every 3 weeks for a minimum of three cycles. A total of 511 cycles were given with a median of five cycles per patient. 20 out of the 90 patients evaluable for response achieved a partial response (PR) (22%, 95% Confidence Interval (CI): 17-36%), 43 (48%) remained stable and 27 showed progression (30%). The mean duration of response was 24 weeks and the progression-free interval was 15 weeks. The overall median survival was 41 weeks. 31 patients (39%, 95% CI: 28-50%) experienced a clinical benefit (improvement of the performance status without a worsening of symptoms or relief of symptoms without a worsening of the performance status). The main toxicities were gastrointestinal and haematological. 12 patients (13%) developed grade 3-4 side-effects: 7 had nausea/vomiting (8%), 6 a transaminase increase (7%), 4 asthenia (4%), 3 diarrhoea (3%), 2 neutropenia (2%), 2 anaemia (2%) and 1 thrombocytopenia (1%). Three toxic deaths occurred (3%). The group of patients with a creatinine clearance <or=1.08 ml/s was found to have a higher risk of developing grade 3-4 toxicity compared with those with adequate renal function (8/18 versus 4/72; P<0.001). In conclusion, raltitrexed is an active, convenient and low toxicity treatment for the elderly with advanced colorectal cancer. However, it must be used cautiously in elderly patients with a creatinine clearance <or=1.08 ml/s since they are at a higher risk of suffering grade 3-4 toxicity.

Age Factors↗

PubMed2001

Phase II trial of paclitaxel plus gemcitabine in patients with locally advanced or metastatic non-small-cell lung cancer.

PURPOSE: Given the cisplatin-related myelotoxicity and nonhematologic toxicities, we were prompted to undertake a study of the noncisplatin combination of paclitaxel plus gemcitabine to evaluate the efficacy, tolerance, and survival of this combination in patients with locally advanced and metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients received gemcitabine 2,000 mg/m(2) and paclitaxel 150 mg/m(2) on days 1 and 15 of a 28-day cycle, for a maximum of eight cycles. RESULTS: Between December 1997 and June 1998, 89 untreated NSCLC patients were enrolled; 30 (34%) had stage IIIB disease (23 with malignant pleural effusion and seven without), and 59 (66%) had stage IV disease. Eighty-six percent of patients had a performance status of 0 or 1. The median number of cycles administered was four (range, one to eight cycles). The mean dose-intensity for both paclitaxel and gemcitabine was nearly 100%. Hematologic and nonhematologic toxicities were mild. Thirty-eight patients received second-line chemotherapy after completion of the study. The overall intent-to-treat response rate was 32.2%, with a higher response rate for stage IIIB patients (43.3%) than for stage IV patients (26.3%). Overall median survival was 9.9 months, and 1-year survival was 38.8% (14.2 months for stage IIIB and 7.7 months for stage IV; P =.007). Median survival was 10.2 months for patients with a performance status of 0 or 1 and 4.8 months for patients with a performance status of 2 (P =.007). CONCLUSION: A biweekly paclitaxel/gemcitabine regimen was well tolerated, with an acceptable response rate and a reasonable median survival time, especially in patients with good performance status. It merits further exploration in future studies.

Adult↗

PubMed2001

Purification and characterization of a proteinase inhibitor from white croaker skeletal muscle (Micropogon opercularis).

A trypsin proteinase inhibitor has been purified to homogeneity from the skeletal muscle of white croaker (Micropogon opercularis). Previously, we had described the occurrence in fish muscle of a serine protease (proteinase I) which showed a great capacity to degrade whole myofibrils in vitro and an endogenous inhibitor that prevented the action of the protease, both on natural and artificial substrates. In this paper, we report the purification and further biochemical characterization of the endogenous trypsin inhibitor. The purification was carried out by DEAE-Sephacel, Con A-Sepharose, Sephacryl S-300 and Mono Q. Throughout the purification procedure, trypsin inhibitory activity was assayed using azocasein as substrate. The molecular mass of the inhibitor was 65 kDa, as estimated by SDS-PAGE and gel filtration. The trypsin inhibitor is a glycoprotein, as deduced by the fact that it binds to Con A-Sepharose and stains with PAS and showed a wide range of pH stability (from 5 to 11). The thermal stability of the inhibitor considerably decreased at temperatures >60 degrees C. Assays of the inhibitor against various proteases indicated that it is highly specific for serine proteases, since it did not inhibit proteases belonging to any other groups. The inhibitor was able to inhibit the endogenous target enzyme (proteinase I) in a dose-dependent manner, with a 50% inhibition at a molar ratio close to 1. The present work contributes to improving our understanding of the physiological role of the proteinase I-inhibitor system in muscle protein breakdown, as well as its influence on post mortem proteolysis.

Animals↗

PubMed2001

Estrogen modulates alpha(1)/beta-adrenoceptor- induced signaling and melatonin production in female rat pinealocytes.

Nocturnal rise in pineal melatonin output is due to the night-induced acceleration of noradrenergic transmission and alpha(1)- and beta-adrenoceptor activation. In addition, in female animals, cyclic oscillations in circulating levels of sex steroid hormones are accompanied by changes in the rate of pineal melatonin secretion. To investigate whether estrogen directly affects pineal adrenoceptor responsiveness, pinealocytes from 21-day-old ovariectomized rats were exposed to physiological concentrations of 17beta-estradiol (17beta-E(2)) and treated with noradrenergic agonists. Direct exposure to 17beta-E(2) reduced alpha(1)/beta-adrenoceptor-induced stimulation of melatonin synthesis and release. This effect was mediated by an estrogen-dependent inhibition of both beta-adrenoceptor-induced accumulation of cAMP and alpha(1)-adrenoceptor-induced phosphoinositide hydrolysis. Furthermore, estrogen reduced transient Ca(2+) signals elicited in single pinealocytes by alpha(1)-adrenoceptor activation or by potassium-induced depolarization. In the case of beta-adrenoceptor responsiveness, neither forskolin- nor cholera toxin-induced accumulation of cAMP were affected by previous exposure to 17beta-E(2). This indicates that estrogen effects must be exerted upstream from adenylylcyclase activation, and independent of modifications in G protein expression, therefore suggesting changes in either adrenoceptor expression or receptor-effector coupling mechanisms. Since estrogen effects upon adrenoceptor responsiveness in pineal cells was not mimicked by 17beta-E(2) coupled to bovine serum albumin and showed a latency of 48 h, this effect could be compatible with a genomic action mechanism. This is also consistent with the presence of two estrogen receptor proteins, alpha- and beta-subtypes, in female rat pinealocytes under the present experimental conditions.

Action Potentials↗

PubMed2001

Clinical features of pharyngeal cancer: a retrospective study of 258 consecutive patients.

Pharyngeal cancer still presents an unsatisfactory mortality (30-40 per cent in most series, with a slightly better prognosis for nasopharyngeal cancer relative to both oropharyngeal and hypopharyngeal cancers) despite advances in treatment. Therefore, it is critical to know the clinical features of pharyngeal cancer. The purpose of this study was to investigate the most relevant clinical features of pharyngeal cancer (oropharyngeal, hypopharyngeal, and nasopharyngeal) in order to improve knowledge of this malignancy with the aim of ameliorating diagnosis and treatment. The retrospective study was based on a review of medical records from 258 consecutive patients with pharyngeal cancer (oropharyngeal, hypopharyngeal and nasopharyngeal) diagnosed at La Paz University Hospital, Madrid, Spain, between January 1 1991 and and December 31 1995. Medical records were provided by the Departments of Otorhinolaryngology, Head and Neck Surgery, Radiation Oncology, and Medical Oncology. All medical records were analysed for the following clinical variables: 1) incidence, 2) sociodemographics, 3) sites (oropharynx, hypopharynx, nasopharynx) and subsites, 4) clinical and histological staging, 5) pathology, 6) presenting symptoms, 7) time to diagnosis, 8) patients' general performance status at diagnosis, 9) personal cancer history and synchronous head and neck tumours, 10) premalignant lesions, and 11) paediatric cases. Our most outstanding finding was the excessively long time that elapsed between first clinical manifestation appearance and conclusive diagnosis of pharyngeal cancer (4.7 months for pharynx, 4.5 for oropharynx, 4.4 for hypopharynx and 6.5 for nasopharynx cancers). It was found that nasopharyngeal cancer was quite different from both oropharyngeal and hypopharyngeal cancers with respect to its potential aetiology, risk factors and clinical presentation. In addition it has a better prognosis.

Adolescent↗

PubMed2001

Novel approaches in the treatment of non-small-cell lung cancer.

A wealth of data indicates that certain genetic abnormalities can target specific cytotoxic drugs and intervene at an early step as a mechanism of resistance in the treatment of non-small-cell lung cancer. Therefore prescribing certain combinations of cytotoxic anticancer agents to a vast majority of these patients is futile. Genetic abnormalities have been found to be useful surrogate markers for response, particularly in colorectal cancer: thymidylate synthase mRNA and ERCC1 mRNA levels. In addition, beta-tubulin mutations may also confer paclitaxel resistance in patients. An important target to be explored for gemcitabine resistance is the assessment of a particular region in chromosome 11p15.5 wherein lies the ribonucleotide reductase gene that could affect gemcitabine metabolism. Shedding light on this genetic framework, several proposed customized chemotherapy studies could help validate the relevance of these markers.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Nitric oxide inhibits tyrosine hydroxylase of rat median eminence.

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the biosynthesis of catecholamines. In a previous report we found that intracerebroventricular administration of nitric oxide (NO) generator sodium nitroprusside (SNP) to conscious male rats inhibited dose-dependently the TH activity of the median eminence (ME). In the present study we have tested the in vitro effects of SNP on TH activity, its possible mediator and action mechanism. Exposure of the ME TH to SNP (50, 100 and 500 microM) caused concentration-dependent inhibition of its enzyme activity. Addition of; reduced hemoglobin Hb (10 microM), a NO scavenger, superoxide dismutase SOD (1000 units/ml), a superoxide scavenger enzyme, or uric acid UA (300 microM), a peroxynitrite scavenger, did not affect the enzyme activity by themselves, but prevented the inhibitory effect of SNP 500 microM. However, the presence of methylene blue MB (100 microM), a guanylyl cyclase inhibitor, did not alter either basal enzyme activity or the inhibitory action of SNP 500 microM. These results suggest that this action of SNP on TH of the ME would be mediated by peroxynitrite generated by the reaction of NO with superoxide.

Animals↗

PubMed2000

Extracellular protease of Natrialba magadii: purification and biochemical characterization.

A serine protease secreted by the haloalkaliphilic archaeon Natrialba magadii at the end of the exponential growth phase was isolated. This enzyme was purified 83 fold with a total yield of 25% by ethanol precipitation, affinity chromatography, and gel filtration. The native molecular mass of the enzyme determined by gel filtration was 45 kDa. Na. magadii extracellular protease was dependent on high salt concentrations for activity and stability, and it had an optimum temperature of 60 degrees C in the presence of 1.5M NaCl. The enzyme was stable and had a broad pH profile (6-12) with an optimum pH of 8-10 for azocasein hydrolysis. The protease was strongly inhibited by diisopropyl fluorophosphate (DFP), phenylmethyl sulfonylfluoride (PMSF), and chymostatin, indicating that it is a serine protease. It was sensitive to denaturing agents such as SDS, urea, and guanidine HCl and activated by thiol-containing reducing agents such as dithiotreitol (DTT) and 2-mercaptoethanol. This protease degraded casein and gelatin and showed substrate specificity for synthetic peptides containing Phe, Tyr, and Leu at the carboxyl terminus, showing that it has chymotrypsin-like activity. Na. magadii protease presented no cross-reactivity with polyclonal antibodies raised against the extracellular protease of Natronococcus occultus, suggesting that although these proteases share several biochemical traits, they might be antigenically unrelated.

Amino Acid Sequence↗

PubMed2000

Preoperative high-dose cisplatin versus moderate-dose cisplatin combined with ifosfamide and mitomycin in stage IIIA (N2) non small-cell lung cancer: results of a randomized multicenter trial.

Preoperative chemotherapy has become an accepted treatment for stage IIIA (N2) non small-cell lung cancer (NSCLC). The majority of induction regimens employ cisplatin, although the importance of cis-platin dose in combination is unclear. A randomized trial was conducted to address whether higher pre-operative cisplatin doses result in improved survival and increased pathologic complete response in NSCLC. Patients with stage IIIA clinically enlarged and biopsy-proven N2 lesions were randomly assigned to receive either high-dose cisplatin (HDCP) (100 mg/m2) or moderate-dose cisplatin (MDCP) (50 mg/ m2) in combination with ifosfamide (3 g/m2) and mitomycin (6 mg/m2). Disease was restaged after 3 cycles, and those patients with response or stable disease underwent thoracotomy. From March 1993 to February 1997, 83 patients were randomized: 46 received HDCP, and 37 received MDCP. Clinical characteristics were well matched. Radiographic response rate was 59% for HDCP patients and 30% for MDCP patients (P = 0.01). Thoracotomy was performed in 71 patients (86%), 58 of whom had resectable disease. Complete resection rate was 61% in the HDCP group, and 51% in the MDCP group (P = 0.5). Postoperative mortality was 11%. Pathologic complete response was observed in one patient who received MDCP. Median survival in the HDCP and MDCP groups was 13 and 11 months, respectively (P = 0.3). In conclusion, higher radiographic response rate is observed in patients who receive HDCP, but this study fails to show any significant improvement in either overall survival or pathologic complete response in this group of patients.

Clinical Trial↗

PubMed1999

Simultaneous involvement of the jejunum and the colon by type-1 neurofibromatosis.

Type-1 neurofibromatosis (NF-1) or Von Recklinghausen disease is an autosomal dominant hereditary condition that may affect the gastrointestinal tract in 25% of cases and which takes three main forms: ganglioneuromatosis, stromal tumors, and tumors in the duodenum and periampullar region. Not infrequently, these patients present with gastrointestinal bleeding. We present the case of a 48-year-old patient diagnosed as having NF-1, with relapsing episodes of gastrointestinal hemorrhage, in which we discovered the simultaneous presence of a stromal tumor in the jejunum together with polypoid and diffuse ganglioneuromatosis in the colon.

Colon↗