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Biomedical subjects

B Bermejo

Publications and source records attributed to B Bermejo.

At least 19 recordsLinked to original sources
PubMed1997

Carboplatin-based versus cisplatin-based chemotherapy in the treatment of surgically incurable advanced bladder carcinoma.

BACKGROUND: The carboplatin-based chemotherapeutic regimen M-CAVI (methotrexate, carboplatin, and vinblastine) is active against bladder carcinoma and can be administered to patients who are ineligible to receive cisplatin or doxorubicin. The authors designed a randomized study to evaluate whether M-CAVI offers a therapeutic advantage over the cisplatin-based regimen M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) in the treatment of patients with surgically incurable advanced bladder carcinoma. METHODS: Patients with surgically incurable advanced bladder carcinoma were enrolled on a randomized trial comparing M-CAVI, which consists of carboplatin (300 mg/m2 on Day 2, adjusted using Calvert's formula for an area under the curve of 5), methotrexate (30 mg/m2 on Days 1, 15, and 22), and vinblastine (3 mg/m2 on Days 2, 15, and 22) administered every 28 days, versus standard M-VAC. The eligibility criteria included histologically proven bladder carcinoma, surgically incurable disease, and no prior chemotherapy. Patients were treated until disease progression or unacceptable toxicity occurred. RESULTS: From January 1989 to January 1994, 47 assessable patients were included. Seventeen patients had lymph node disease and 30 had distant metastatic disease. Twenty-three patients were randomized to receive M-CAVI and 24 to receive M-VAC. Patient characteristics in the two groups were similar. Overall response rates were 39% (95% confidence interval [CI], 20-62%) for M-CAVI and 52% (95% CI, 30-73%) for M-VAC (P = 0.3), with 3 complete responses observed among patients treated with M-VAC and none among those in the M-CAVI group. M-VAC was associated with more gastrointestinal toxicity, stomatitis, alopecia, and Grade 4 neutropenia than M-CAVI. One toxicity-related death occurred in the M-VAC group. There was a statistically significant difference in median disease-related survival time favoring M-VAC (16 months; range, 6 to 22+) versus M-CAVI (9 months; range, 6 to 14+) (P = 0.03). CONCLUSIONS: M-CAVI is less toxic but less active than M-VAC in the treatment of patients with advanced bladder carcinoma. Carboplatin-based regimens in which carboplatin is administered at the dose range used in the current study should be reserved for patients who cannot tolerate cisplatin treatment. Further research is required to assess the impact of high dose carboplatin in the treatment of this disease.

Adult↗
PubMed1997

Eicosanoids and fat emulsions in acute respiratory distress syndrome patients.

Lipid emulsions have been associated with changes in pulmonary function. Although these changes were related to the physical effects of the infusion-induced lipemia on gas exchange, several animal and human studies suggest that the impairment in pulmonary function observed with lipid infusions was mediated by prostaglandins. Prostaglandins are synthesized enzymatically from essential fatty acids. We studied the effects of two lipid emulsions, with different amounts of essential fatty acids (20% long-chain triacylglycerols [LCT] with 55% of linoleic acid and 7% of alpha linolenic acid in 100 g of emulsion, and a physical mixture of 20% medium-chain triacyglycerols [MCT] and LCT with 26% of linoleic acid and 4% of alpha linolenic acid in 100 g of emulsion), on plasma levels of eicosanoids in patients with acute respiratory distress syndrome (ARDS). Although in patients with ARDS, plasma levels of prostanoids were higher than the reference values, neither lipid emulsion, administered at the rate of 2 mg.kg-1.min-1 induced significant changes in the eicosanoids except for a decrease in systemic-pulmonary arterial 6-keto prostaglandin F1 alpha difference.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Effects of smoking on the presentation and clinical course of inflammatory bowel disease.

OBJECTIVE: To evaluate the influence of regular smoking on the presentation and clinical course of inflammatory bowel disease. METHODS: We performed a case-control study interviewing 160 inflammatory bowel disease patients (63 with Crohn's disease (CD) and 97 with ulcerative colitis (UC)) and 140 first-degree relatives as controls. The risk of developing the disease relative to a smoking habit was calculated as the odds ratio. Furthermore, to evaluate the influence of smoking on the subsequent course of inflammatory bowel disease, we performed a multivariate analysis that included pertinent variables such as the need for surgery, number of hospitalizations and relapses. RESULTS: The pattern of smoking in UC patients was different from that in CD patients. In UC there was a significant predominance of non-smokers and ex-smokers (P = 0.02), whereas smoking habits in CD were not different from those in controls. Giving up smoking was a risk factor to develop UC (odds ratio: 3.2, P = 0.02). In UC, non-smokers and specially ex-smokers need surgery more frequently than smokers (P < 0.01). Otherwise the relapse/year index was not influenced by smoking. In CD there was a non-significant association between smoking habits and the various clinical parameters analysed. UC patients who begin smoking after diagnosis of the disease present a significant reduction in the number of recurrences. CONCLUSION: Smoking habit significantly affects the presentation and clinical course of UC, whereas in CD, a smoking habit does not have any apparent influence on the disease.

Adult↗
PubMed1997

Frequent dose delays and growth factor requirements with the sequential doxorubicin-CMF schedule.

Doxorubicin for four cycles plus cyclophosphamide, methotrexate and 5-fluorouracil (CMF) for eight cycles is an effective adjuvant regimen for breast cancer patients with more than three involved axillary lymph nodes. We reviewed the incidence of dose delays and growth factor requirements when this regimen is administered to patients receiving concurrent irradiation. Thirty-six patients with more than three involved axillary lymph nodes were treated with the sequential regimen doxorubicin-CMF and irradiation. Patients with two or more dose delays received G-CSF treatment. Seventy-five percent of the patients required dose delays for day-22 neutropenia, and growth factors were needed for half of the patients in order to maintain a received dose intensity of 0.940. The first delayed cycle occurred in 74% of the patients while receiving concomitant chemoradiotherapy. Frequent dose delays were required when the sequential regimen doxorubicin-CMF was administered along with radiotherapy. Growth factors are needed to maintain dose intensity similar to that achieved in the original trial.

Adult↗
PubMed1997

Seasonal influence in exacerbations of inflammatory bowel disease.

Several epidemiological studies have suggested a possible seasonality in the presentation and course of inflammatory bowel disease. Our aim was to investigate whether in our area there is a seasonality in the presentation and evolution of inflammatory bowel disease. In this retrospective evaluation 255 patients were included, of whom 141 patients were diagnosed with ulcerative colitis and 114 with Crohn's disease according to conventional criteria, with histological confirmation in 225 patients. Relapse was defined as the development of symptoms that required an increase or change in the usual treatment. Periods of activity were related to the month and grouped within one of four seasonal periods: December to February, March to May, June to August and September to November. Bouts of ulcerative colitis and Crohn's disease were most frequently diagnosed in the period June to August (p < 0.05). Both diseases showed similar seasonality, and analysis of the 305 attacks did not show any significant trend. In conclusion, inflammatory bowel disease begins more frequently in the period June to August, but its course does not show consistent seasonal variations.

Adolescent↗
PubMed1996

[Serologic study in patients with streptococcal infective endocarditis].

BACKGROUND: Infective endocarditis is a systemic disease in which there are a continuously antigenic stimulation of immunologic system. Streptococcus is still the most frequent cause of infective endocarditis. PATIENTS AND METHODS: We investigated the presence of antibody (AB), total and IgM by indirect immune fluorescence technique, in four groups of population: streptococcal infective endocarditis (SIE), streptococcal bacteraemia (SB), Staphylococcus aureus endocarditis, and healthy people. Antigens used were: 1) their own strain isolated from the blood of patients with SIE and SB ¿homologous AB¿, and; 2) seven species of Streptococcus: Streptococcus intermedius, Streptococcus salivarius, Streptococcus bovis, Streptococcus sanguis I, Streptococcus sanguis II, nutritional dependent streptococci and Enterococcus faecalis (heterologous AB). RESULTS: Homologous antibodies: titers > or = 1/512 were found in all patients with SIE and only in 2 with SB (sensitivity 100% and specificity 93%). IgM titer (threshold 1/32) was positive only in patients with SIE (sensitivity 75,5% and specificity 100%). The fall of the AB titer was continuous and slow, despite the good clinical evolution of patients. (AB titers were > or = 1/512 and IgM > or = 1/64 in 30% of patients 1 year later). Heterologous AB: in spite of statistically significant difference found in SIE versus the other groups, sensitivity of this test (threshold 1/256) is low, confidence interval include expected random value (50%), specificity is 88%. CONCLUSIONS: The utility of homologous AB for diagnosing infective endocarditis is demonstrated. On the contrary for heterologous AB, antigenic common fractions must be found in the different species.

Adult↗
PubMed1996

Repeated 15-minute coronary occlusions in pigs increase occlusion arrhythmias but decrease reperfusion arrhythmias that are associated with extracellular hypokalemia.

OBJECTIVES: We sought to evaluate the effects of repetitive 15-min coronary occlusions followed by 45-min reperfusions on the incidence of occlusion and reperfusion arrhythmias in pigs. BACKGROUND: Brief 2- to 5-min coronary occlusions seem to exert a protective effect on occlusion and reperfusion arrhythmias. However, because clinical ischemic episodes are often longer, it would be appropriate to assess whether such protection also occurs when longer cycles of occlusion-reperfusion are produced. METHODS: Three to four cycles of 15-min coronary occlusions with 45-min reperfusions were performed in 34 pigs, and changes in ST segment and incidence of ventricular arrhythmias were assessed. Plasma potassium ion concentrations in eight pigs and blood gas in six were measured from blood from the ischemic area during reperfusion. RESULTS: Repetitive occlusions were associated with a progressively higher ST segment elevation and a higher incidence of ST segment alternans (p < 0.001) and ventricular fibrillation (VF) (p < 0.01). However, during repetitive reperfusions, normalization of the ST segment was increasingly faster, the incidence of VF was progressively reduced (p < 0.03), and there was progressively less severe regional acidosis ([mean +/- SD] 7.06 +/- 0.12 vs. 7.26 +/- 0.06, p < 0.05) and hypokalemia (1.9 +/- 0.7 vs. 2.3 +/- 0.4 mEq/liter, p = NS). CONCLUSIONS: The progressive electrocardiographic deterioration and increasing incidence of ventricular arrhythmias during repetitive 15-min occlusions in pigs suggest increasing metabolic derangement. However, the progressively faster normalization of the ST segment and the reduced incidence of ventricular arrhythmias during reperfusion suggest an increasingly faster restoration of the metabolic and ionic balance.

Acid-Base Equilibrium↗
PubMed1996

[Cost-effectiveness analysis of serum ferritin screening in periodic physical examinations of women at the fertile age].

BACKGROUND: Fertile-aged women are a population group at special risk for developing ferropenia. In the periodic health care examinations, hemogram, among other tests, are included to detect the most advanced state of iron deficity, ferropenic anemia. Likewise, preanemic ferropenia presents a certain morbidity. The aim of this study was to analyze the cost-effectiveness of screening serum ferritin determination in health care examinations of fertile-aged women. SUBJECTS AND METHODS: An observational transversal study was carried out in 322 women in whom hemogram and serum ferritin were determined. The effects of serum ferritin determination were simulated in a hypothetical cohort of 20-year old women annually examined up to the age of 50 years (mean age of menopause). RESULTS: The prevalence of preanemic ferropenia (serum ferritin < or = ng/ml) was 44.1% and that of ferropenic anemica (Hb < 120 g/l and serum ferritin < or = 25 ng/ml) was 3.4%. Hemogram sensitivity for detection of ferropenia was 7.2% (3.6-12.5). By means of the screening program with serum ferritin avoiding of one year with ferropenia costs 2,428 pesetas. Prolonging the program to longer than 35 years largely increases the marginal cost. Cost-effectiveness analysis is specially sensitive to the cost of the diagnostic tests and disease prevalence. CONCLUSIONS: Ferropenia in fertile-aged women is a frequent disorder. Avoiding ferropenia by early diagnosis may be performed at a relatively low cost.

Adult↗
PubMed1996

Additional elevation of the ST segment: a possible early electrocardiographic marker of experimental myocardial reperfusion.

OBJECTIVE: To analyze the early electrocardiographic changes during experimental coronary reperfusion after 1 to 4 h of coronary occlusion. METHODS: Recordings of epicardial and endocardial DC electrograms were performed in 35 open-chest pigs during coronary occlusions of 1 to 4 h duration followed by 1 h of reperfusion. RESULTS: During occlusion, maximal ST segment elevation was reached between min 10 and 30 which was followed by and a steady decline. During the first 30 min of reperfusion, however, there was a further elevation of the ST segment with a peak at 5 min. Thus, values at the end of occlusion and at 5 min of reperfusion were: (a) group with 1 h occlusion (n = 11), 15.5 +/- 7 and 37.4 +/- 11.4 mm, P < 0.005; (b) group with 2 h occlusion (n = 6), 10.2 +/- 4 and 24.7 +/- 9.4 mm, P < 0.03; (c) group with 3 h occlusion (n = 6), 7.5 +/- 3 and 16.8 +/- 5.6 mm, P < 0.03; and (d) group with 4 h occlusion (n = 12), 6.4 +/- 2.4 and 17.0 +/- 8.9 mm, P < 0.01. In 9 animals from the group with 1 h occlusion, a second cycle of 1 h occlusion and reperfusion also showed re-elevation of ST segment during reperfusion, although to a lesser extent than the first one (from 10.0 +/- 4.9 to 16.3 +/- 7.1 mm, P < 0.01). CONCLUSIONS: Thus, our findings provide experimental evidence of an additional and paradoxical ST segment elevation as the earliest electrocardiographic sign of coronary reperfusion after 1 to 4 h of coronary occlusion. These observations may help to improve the interpretation of early electrocardiographic changes during thrombolysis in acute myocardial infarction.

Animals↗
PubMed1996

M-CAVI, a neoadjuvant carboplatin-based regimen for the treatment of T2-4N0M0 carcinoma of the bladder.

Carboplatin, methotrexate, and vinblastine (M-CAVI) is an active and well-tolerated regimen for bladder cancer patients ineligible for cisplatin-based regimens. We treated 47 T2-4 N0 M0 bladder cancer patients with M-CAVI in a neoadjuvant phase II trial. These 47 patients are evaluable for clinical response and toxicity. Clinical overall response rate was 34%, for a 95% confidence interval (CI95%) of 21-49%. Pathological response was seen in 40% of the patients (CI95%, 26-56%) with a 26.5% rate of pathological complete response (CI95%, 15-42%). Factors associated with the achievement of a response to therapy were the initial TNM stage (pT3a or lower, greater than pT3a, p = 0.001) and a Karnofsky score greater or equal than 90%, which was marginally significant (p = 0.08). With a median follow-up of 14 months, the disease-specific actuarial survival at 2 years is 42%. No patient has relapsed beyond 21 months of follow-up in a disease-free status. Toxic effects have been moderate. In conclusion, M-CAVI is an active and well-tolerated regimen that should be compared in terms of response rate and survival with a cisplatin-based regimen for invasive bladder cancer.

Actuarial Analysis↗
PubMed1996

Five-day course of granulocyte colony-stimulating factor in patients with prolonged neutropenia after adjuvant chemotherapy for breast cancer is a safe and cost-effective schedule to maintain dose-intensity.

PURPOSE: To analyze the safety and efficacy of a short course of granulocyte colony-stimulating factor (G-CSF) to maintain dose-intensity of subsequent cycles of chemotherapy after a prior episode of prolonged neutropenia, without febrile complications, in patients receiving adjuvant treatment for breast cancer. PATIENTS AND METHODS: Thirty-two patients undergoing adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) or doxorubicin-CMF for stages I to II breast cancer were included after having chemotherapy delays due to neutropenia (absolute neutrophil count [ANC] < 1.5 x 10(9)/L) on day 22. G-CSF was administered subcutaneously on days 15 to 19 of each subsequent cycle. RESULTS: None of the patients included in this study had to be admitted to the hospital for fever and neutropenia. The median percentage of the projected dose-intensity for CMF or doxorubicin-CMF on an intent-to-treat basis was 0.994, which was significantly higher than the delivered dose-intensity before the start of G-CSF treatment (P < .0001). Patients who received concomitant G-CSF and radiotherapy achieved a similar dose-intensity as patients who did not undergo radiotherapy. Seven patients discontinued G-CSF treatment due to musculoskeletal pain. These patients had more subsequent cycle delays because of day 22 neutropenia than the 25 patients who followed the G-CSF schedule (P = .0028). CONCLUSION: A 5-day course of G-CSF in patients with prior chemotherapy delays due to prolonged neutropenia seems to be a safe and cost-effective schedule to maintain CMF or doxorubicin-CMF dose-intensity in the adjuvant treatment of breast cancer.

Adult↗
PubMed1996

[Prevalence of iron deficiency in the female working population in the reproductive age].

INTRODUCTION: Iron deficiency is particularly common among women in child-bearing age. The early detection and institution of an appropriate therapy can prevent the development of anemia. OBJECTIVE: To study the prevalence of iron deficiency among women in child-bearing age (in the setting of periodic health visits) and the associated risk factors. SAMPLE AND METHODS: A cross-sectional observational study was undertaken with 322 women in child-bearing age. An hemogram and serum ferritin levels were obtained on the same day when an interview was carried out to obtain data on general personal details, gynecological-obstetrical antecedents, diet, sports, and blood donations. Iron deficiency was defined as a serum ferritin concentration lower than 25 ng/ml. RESULTS: The prevalence of iron deficiency was 47.5%. In the multivariate analysis, factors significantly influencing on prevalence were: a copious menstruation blood loss (OR = 4.64, CI 2.22-9.68), a body mass index higher than 25 (OR = 0.49; CI 0.27-0.89) and maternity (OR = 2.08; CI 1.12-3.84). The likelihood associated with chi square goodness-of-fit was 0.08. DISCUSSION: The prevalence of iron deficiency detected is high; although there are clear associated risk factors, the goodness-of-fit was poor; therefore, for predictive purposes it is not possible to delineate a group in a special risk for iron deficiency.

Adolescent↗
PubMed1995

[Thrombocytopenia onset in acute episodes of pancreatitis].

BACKGROUND: The objective of this study was to determine the prevalence of thrombocytopenia in acute pancreatitis and its value as a prognostic marker for complications. METHODS: The records of all patients admitted to our institution between January and June 1993 were reviewed. After exclusion of other possible causes of thrombocytopenia, 104 patients were evaluated. The prognostic value of thrombocytopenia was determined by evaluation of the length of hospital stay, radiologic severity, complications, need for ICU care, need for surgery and mortality. RESULTS: The etiology of pancreatitis was as follows: gallstone-induced in 49 patients, alcoholic in 35, idiopathic in 12 and due to other causes in the remaining 8 cases. Thrombocytopenia developed early, within the first 48 hours and was moderate (106 +/- 27 x 10(9)/l). Alcoholic pancreatitis was associated to a higher probability to develop thrombocytopenia (43% vs 36% in gallstone-induced pancreatitis and 4% in idiopathic pancreatitis, p = 0.02). Thrombocytopenic patients had a greater radiologic severity (Balthazar's scores D or E 78% vs 49%, p = 0.04), a higher number of acute complications (28% vs 10%, p = 0.05) and a more frequent need for ICU care (25% vs 7%, p = 0.01). No differences were seen in length of hospital stay, need for surgery and mortality between the two groups of patients. CONCLUSIONS: Thrombocytopenia is frequent in acute pancreatitis, especially in cases of alcoholic origin. Its presence suggests a higher risk to develop complications.

Acute Disease↗
PubMed1995

Heterologous expression of the highly conserved acidic ribosomal phosphoproteins from Dictyostelium (changed from Dictyosteliumm) discoideum in Saccharomyces cerevisiae.

The genes encoding the acidic ribosomal phosphoproteins DdP1 and DdP2 from Dictyostelium discoideum have been cloned into yeast plasmid vectors under the control of the inducible GAL1 promoter. These constructions have been used to transform S. cerevisiae strains D45 and D67 lacking the equivalent ribosomal components. The D. discoideum genes are properly transcribed when cells are grown in the presence of the inducer galactose and the mRNAs incorporated into polysomes. However, the heterologous ribosomal proteins are not able to rescue the growth deficiency in S. cerevisiae caused by the absence of their own ribosomal proteins. When the heterologous proteins are analyzed using specific antibodies, only protein DdP1 is found in the ribosomes of the transformed S. cerevisiae D67 strain. No other heterologous protein is found in any other transformed strain, suggesting that the heterologous acidic ribosomal components are rapidly degraded when they are not bound to the ribosomes. The results indicate that D. discoideum DdP1 protein is able to interact with the yeast ribosome, though the interaction is functionally inefficient. Protein DdP2, in spite of having a higher sequence similarity to its yeast counterparts, is completely inactive in S. cerevisiae. Since the P proteins from both organisms have extensive amino acid sequence similarity ranging from 60% to 70%, these results warns about establishing a direct relationship between the extent of amino acid sequence similarity and the capacity of heterologous proteins to be functional in host species. Moreover, our data suggest that evolution affected the interaction of the acidic proteins with the ribosome rather than the structural features responsible for their primary functions.

Amino Acid Sequence↗
PubMed1995

Overexpression of c-erbB-2 in epithelial ovarian cancer. Prognostic value and relationship with response to chemotherapy.

BACKGROUND: Overexpression of the c-erbB-2 protein has been reported in tumors from approximately 25% of patients with epithelial ovarian cancer. However, its clinical significance has not been well established. METHODS: Overexpression of the c-erbB-2 protein was studied by immunohistochemistry in paraffin-embedded tumor tissue from 106 patients with ovarian cancer. RESULTS: Tumors from 23 patients (21.7%) had c-erbB-2 overexpression. The percentage of tumors with overexpression was higher in those with Stages III/IV disease (29.2%) compared with those with Stages I/II disease (5.9%) (P = 0.057), in patients with residual tumor greater than 2 cm after initial surgery (37.2%) compared with those with tumor less than 2 cm (9.5%) (P = 0.01), and in patients who failed to respond to chemotherapy with carboplatin and cyclophosphamide (75%) compared with those who responded (18.6%) (P = 0.0043). No correlation was found between c-erbB-2 expression with age, the degree of differentiation, or the histologic subtype. Median survival of the 23 patients with protein overexpression was 62 weeks, whereas 75% of the 83 patients without overexpression were alive at 123 weeks (P = 0.0000). Of the patients with advanced stage disease (III/IV), survival was also lower in those presenting with overexpression (60 weeks) compared with those without expression (75% alive at 93 weeks) (P = 0.0000). Multivariate analysis of possible prognostic factors showed that c-erbB-2 overexpression and residual tumor greater than 2 cm resulted in a worsening of survival rates. CONCLUSION: c-erbB-2 overexpression in tumors from patients with ovarian cancer resulted in a poorer prognosis than for patients whose tumors did not have overexpression.

Adult↗
PubMed1995

Ribosomal acidic phosphoproteins P1 and P2 are not required for cell viability but regulate the pattern of protein expression in Saccharomyces cerevisiae.

Saccharomyces cerevisiae strains with either three inactivated genes (triple disruptants) or four inactivated genes (quadruple disruptants) encoding the four acidic ribosomal phosphoproteins, YP1 alpha, YP1 beta, YP2 alpha, and YP2 beta, present in this species have been obtained. Ribosomes from the triple disruptants and, obviously, those from the quadruple strain do not have bound P proteins. All disrupted strains are viable; however, they show a cold-sensitive phenotype, growing very poorly at 23 degrees C. Cell extracts from the quadruple-disruptant strain are about 30% as active as the control in protein synthesis assays and are stimulated by the addition of free acidic P proteins. Strains lacking acidic proteins do not have a higher suppressor activity than the parental strains, and cell extracts derived from the quadruple disruptant do not show a higher degree of misreading, indicating that the absence of acidic proteins does not affect the accuracy of the ribosomes. However, the patterns of protein expressed in the cells as well as in the cell-free protein system are affected by the absence of P proteins from the particles; a wild-type pattern is restored upon addition of exogenous P proteins to the cell extract. In addition, strains carrying P-protein-deficient ribosomes are unable to sporulate but recover this capacity upon transformation with one of the missing genes. These results indicate that acidic proteins are not an absolute requirement for protein synthesis but regulate the activity of the 60S subunit, affecting the translation of certain mRNAs differently.

Cell Differentiation↗
PubMed1994

Effect of acidic ribosomal phosphoprotein mRNA 5'-untranslated region on gene expression and protein accumulation.

Constructions were made from genes encoding ribosomal acidic phosphoproteins YP1 beta (L44') and YP2 beta (L45) from Saccharomyces cerevisiae in which different parts of the 5'-untranslated regions were included. The constructs were inserted into centromeric plasmids under the control of the GAL1 promoter and expressed in yeast strains in which the genes coding for each acidic protein family, P1 and P2, had been disrupted. Deletions in the 5' region of the two genes have been found to oppositely affect their expression. Deletion of most of this region strongly stimulates the expression of YP2 beta (L45), increasing the translation efficiency of the mRNA, and generating a 6-fold excess of protein in the cell. A similar deletion in the rpYP1 beta gene represses the expression of the protein, reducing drastically the amount of the mRNA in the cell. The overexpression of rpYP2 beta affects the cell growth by inhibiting protein synthesis at the level of initiation. Reduction of the YP2 beta(L45) overproduction by growing in controlled concentrations of glucose abolishes the inhibitory effect. The excess protein, probably as a high molecular weight complex, apparently interferes with the joining of the 60 S subunit to the initiation complex generating the accumulation of polysome half-mers. In addition, the results indicate the existence of a regulatory mechanism by which each one of the two acidic proteins controls the expression of the other polypeptide. YP1 beta(L44') represses the expression of YP2 beta(L45), while this protein stimulates the expression of YP1 beta(L44').

Gene Expression Regulation, Fungal↗
PubMed1994

Long-term survival in advanced ovarian cancer after cytoreduction and chemotherapy treatment.

Ninety-one patients with untreated epithelial ovarian cancer, stages III and IV, were treated according to a therapeutic protocol including cytoreductive surgery whenever possible, chemotherapy with CAP (cyclophosphamide, doxorubicin, and cisplatin) and second-look laparotomy for those patients achieving a clinical remission. Optimal cytoreductive surgery (residual tumor < 2 cm) was not performed in 66 patients (72.5%). A negative second-look laparotomy demonstrated a pathological complete remission in 26 patients (28.5%). After a median follow-up of 80 months, the disease-free survival is 19.7% (18 of 91 patients). Median survival was greater in optimal cytoreductive surgery patients (47 months) than in the rest of the patients (22 months) (P = 0.0000). Survival was also better in pathological complete remission patients (46 months) than in partial remission (PR) or no response patients (22 months) (P = 0.0001). Optimal secondary cytoreductive surgery was possible in 11 patients in PR after chemotherapy. Survival in this group was similar to that of pathological complete remission cases. Currently, 53% of patients with initial residual tumor < 2 cm and complete response at second-look remain free of disease. In a multivariate analysis, residual tumor > 2 cm and stage IV disease were the most significant prognostic factors. The same analysis indicates that response to chemotherapy at second laparotomy is not an independent prognostic factor. In conclusion, our study indicates that the two most important prognostic factors in advanced ovarian carcinoma are the extent of the initial surgery and stage.

Adult↗