Biomedical subjects

N Flores

Publications and source records attributed to N Flores.

At least 19 recordsLinked to original sources

PubMed1999

The mer operon of the acidophilic bacterium Thiobacillus T3.2 diverges from its Thiobacillus ferrooxidans counterpart.

The chromosomal mercury resistance (mer) region of the acidophilic bacterium Thiobacillus T3.2 was cloned, characterized, and compared to reported homologous sequences. The Thiobacillus T3.2 mer resistance system is organized as an operon that transcribes into a polycistronic mRNA encoding the Hg2+ ion transport MerT and MerP proteins and the mercuric reductase MerA. In contrast to the Thiobacillus ferrooxidans mer determinant, no merC gene was detected. Transcription of structural genes is regulated by the product of the regulatory merR gene. On the basis of sequence data and expression experiments in E. coli, both merTPA and merR transcription units could be located close to each other and in different strands, with their promoters (PTPA and PR, respectively) overlapping the putative MerR binding site in the intergenic operator/promoter (O/P) region. Amino acid sequences of mer gene products were compared to their homologs. Some sequence features, such as the number and position of cysteine residues, are unique for the Mer proteins of this bacterium. Similarities (-10 and -35 boxes are 19bp apart in both PR and PTPA promoters) and differences (inverted repeats in the Thiobacillus T3.2 MerR-binding site are 2bp shorter than in Thiobacillus ferrooxidans) exist between the O/P intergenic regions of both Thiobacilli. In vivo experiments showed inducible expression of mercury resistance in E. coli cells transformed with the entire Thiobacillus T3.2 mer genetic determinant (structural plus regulatory genes), and little or no expression in clones containing only the structural merT, merP, and merA genes.

Amino Acid Sequence↗

PubMed1997

Intravesical immunoprophylaxis in recurrent superficial bladder cancer (Stage T1): multicenter trial comparing bacille Calmette-Guérin and interferon-alpha.

OBJECTIVES: To estimate and compare recurrence rates, index of recurrence, and disease-free interval in patients with superficial recurrent bladder cancer receiving bacille Calmette-Guérin (BCG) or interferon (IFN) for immunoprophylaxis. METHODS: One hundred twenty-two patients with recurrent superficial Stage pT1, grade 1 to 3 tumors were enrolled in a randomized, prospective, multicenter trial with two treatment arms of endovesical immunoprophylaxis: 150 mg of BCG versus 54 MU of recombinant IFN-alpha-2a. Administration was weekly during the first month, biweekly for 2 months, and monthly for 9 months. Both groups were similar with regard to tumor stage, grade, size, and number. RESULTS: Sixty-one patients were evaluable in the BCG group and 49 in the IFN group. Tumors recurred in 34 (69.4%) of 49 patients in the IFN group (890 months of follow-up) and in 24 (39.3%) of 61 in the BCG group (1272 months of follow-up). The total number of recurrences (28 for BCG, 47 for IFN), disease-free interval (mean 19.3 months for BCG, 15.3 months for IFN), and index of recurrence (2.2 for BCG, 5.5 for IFN) were statistically significant (P = 0.001) in favor of BCG. Progression to invasive carcinoma was similar in both study arms. Neither systemic nor local side effects were seen in the IFN group. However, the previously reported toxicity of BCG was confirmed. CONCLUSIONS: According to our trial, BCG remains the most efficacious agent for immunoprophylaxis of recurrent superficial bladder tumors.

Adjuvants, Immunologic↗

PubMed1996

Malignant fibrous histiocytoma of the renal capsule and synchronous transitional cell carcinoma of the bladder.

The synchronous association of malignant fibrous histiocytoma (MFH) of the kidney and transitional cell carcinoma of the urinary bladder is reported. This constitutes the ninth case of MFH definitely arising from the renal capsule. Fever was its first clinical manifestation. Despite complete surgical removal, the tumor was rapidly fatal. The current literature about MFH of the kidney is extensively reviewed.

Aged↗

PubMed1996

Pathway engineering for the production of aromatic compounds in Escherichia coli.

Glucose is the preferred substrate for certain fermentation processes. During its internalization and concomitant formation of glucose-6-phosphate through the glucose phosphotransferase system (PTS), one molecule of phosphoenolpyruvate (PEP) is consumed. Together with erythrose 4-phosphate (E4P), PEP is condensed to form 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP), the first intermediate of the common segment of the aromatic pathway. From this metabolic route, several commercially important aromatic compounds can be obtained. We have selected Escherichia coli mutants that can transport glucose efficiently by a non-PTS uptake system. In theory, this process should increase the availability of PEP for other biosynthetic reactions. Using these mutants, in a background where the DAHP synthase (the enzyme that catalyzes the condensation of PEP and E4P into DAHP) was amplified, we were able to show that at least some of the PEP saved during glucose transport, can be redirected into the aromatic pathway. This increased carbon commitment to the aromatic pathway was enhanced still further upon amplification of the E. coli tktA gene that encodes for a transketolase involved in the biosynthesis of E4P.

3-Deoxy-7-Phosphoheptulonate Synthase↗

PubMed1996

Primary cisplatin, methotrexate and vinblastine aiming at bladder preservation in invasive bladder cancer: multivariate analysis on prognostic factors.

PURPOSE: Although radical cystectomy is the standard therapy for invasive bladder cancer, cisplatin based multi-drug chemotherapy has proved to be effective for advanced transitional cell urothelial carcinoma. The potential for bladder preservation with neoadjuvant chemotherapy is currently under investigation. MATERIALS AND METHODS: A phase 2 protocol is presented for conservative treatment of muscle invasive transitional cell carcinoma of the bladder consisting of primary cisplatin, methotrexate and vinblastine chemotherapy followed by reevaluation for bladder sparing surgery and surveillance. A total of 61 patients completed the protocol with a mean followup of 41.4 months. RESULTS: Initial complete response to chemotherapy associated with tumor stage, size and configuration was noted in 20 patients (33%). Bladder preservation, intended only for the complete response group, was achieved in 16 patients (26%) but only 11 (18%) were alive with the bladder intact at study closure. Disease-free 5-year survival rate was 47% (95% confidence interval 65 to 26%). Tumor stage (p = 0.0007), size (p = 0.0003), response to chemotherapy (p = 0.002), patient age (p = 0.039) and tumor grade (p = 0.048) influenced survival. Multivariate analysis revealed response to chemotherapy (beta = 0.988, p = 0.034) and tumor size (beta = 0.978, p = 0.042) to be the only independent predictors. CONCLUSIONS: Induction of cisplatin, methotrexate and vinblastine chemotherapy is helpful in identifying patients with a greater chance for survival among those with locally advanced bladder cancer. However, a bladder preservation strategy based on this therapy is only of limited success.

Aged↗

PubMed1996

[Prognosis prediction in patients with transitional cell carcinoma of the urinary bladder].

OBJECTIVES: Many attempts have been made during decades to identify factors predictive of prognosis in patients with transitional cell carcinoma (TCC) of the bladder. The present study attempts to determine the predictive factors in a large series of patients with long follow-up homogeneously treated at three institutions from 1983 to 1992. METHODS: The clinical and histological factors with presumed prognostic value were retrospectively evaluated in a series of 331 patients with a mean follow-up of 7.2 years, and a study of survival was performed. RESULTS: Univariate analysis showed tumor stage, growth pattern, grade, size, coexisting dysplasia, histologic type, topography of the lesion and patient age are useful parameters for the prediction of prognosis. The Cox analysis revealed tumor stage is the most important prognostic variable (Beta = 1.23, p < .001), followed by growth pattern as determined by the presence or absence of a papillary phenotype (Beta = 1.18, p < .001), tumor size (Beta = .98, p < .001), WHO modified histologic grading considering persistence or loss of cell polarity (Beta = .73, p < .01), tumor location (Beta = .48, p < .05), and histology (presence or absence of phenotypes other than pure TCC, Beta = .45, p < .05). Coexisting dysplasia, tumor multiplicity, age and sex did not independently influence survival. CONCLUSION: Despite the advancements in the field of molecular biology relative to prognostic markers in bladder cancer, the conventional morphological parameters and tumor stage continue to be the main source of prognostic information in clinical practice.

Adult↗

PubMed1995

Cloning of the two pyruvate kinase isoenzyme structural genes from Escherichia coli: the relative roles of these enzymes in pyruvate biosynthesis.

We report the cloning of the pykA and pykF genes from Escherichia coli, which code for the two pyruvate kinase isoenzymes (ATP:pyruvate 2-O-phosphotransferases; EC 2.7.1.40) in this microorganism. These genes were insertionally inactivated with antibiotic resistance markers and utilized to interrupt one or both pyk genes in the E. coli chromosome. With these constructions, we were able to study the role of these isoenzymes in pyruvate biosynthesis.

Cloning, Molecular↗

PubMed1995

Value of surgical intervention in the treatment of glioma.

The benefit of cytoreductive surgery in the management of glioma remains speculative. We therefore reviewed all confirmed deaths in our Neuro-Oncology Program and examined various clinical factors related to survival. There were 63 patients (34 males/29 females), with an average age of 57.6 years. The pathology was glioblastoma in 44 and anaplastic astrocytoma in 19; median survival was 12 months. Forty patients underwent at least one craniotomy, following which 22.5% achieved a gross total resection, 23 had biopsy only. Only age and gross total resection of tumor as judged by postoperative MR (CT in 2 cases) correlated significantly with outcome. The subtotal craniotomy group and biopsy only cohort were indistinguishable (median survival 11 vs. 10 months, respectively). Although craniotomy associated with gross total resection results in enhanced survival (median 27 months), subtotal tumor excision offers little beyond a diagnosis. Therefore, careful and realistic preoperative assessment of glioma patients ought to be performed to determine optimal surgical management.

Biopsy↗

PubMed1995

Improving the safety of BCG immunotherapy by dose reduction. Cooperative Group CUETO.

The preliminary results of a randomized, multicentre, prospective trial conducted by the Spanish Oncology Group (CUETO) are presented. The primary aim of the trial was to determine whether or not lowering the dose of bacillus Calmette-Guérin (BCG) could reduce toxicity without compromising efficacy. From February 1991 to June 1992, 500 patients with superficial bladder cancer (TaG2-3, T1G1-3) entered the trial. Of these patients, 252 were included in group A (BCG, 81 mg) and 248 in group B (BCG, 27 mg). There were no significant differences in clinical and pathological characteristics between the two groups. Following treatment, significant differences arose between groups A and B in local severe toxicity (22.6 vs. 4.2%, respectively; p < 0.01). Systemic toxicity was more common in group A than in group B (p < 0.01): pulmonary effects (2.3 vs. 0.4%), fever (26.9 vs. 12.9%) and malaise (16.2 vs. 8.4%), all p < 0.01. Regarding efficacy, 204 patients in group A and 210 in group B were evaluated after a mean follow-up of 18.6 months. No significant differences in recurrence rate (18.1 vs. 19.5%) or progression rate (2.4 vs. 4.8%) were found. However, in patients with superficial bladder cancer with high risk of recurrence and progression (carcinoma in situ and G3), caution must be exercised in selecting the dose.

Administration, Intravesical↗

PubMed1995

Neoadjuvant cisplatin chemotherapy before radical cystectomy in invasive transitional cell carcinoma of the bladder: a prospective randomized phase III study.

From November 1984 to April 1989, 122 patients with clinical T2-4a Nx-2 M0 transitional cell carcinoma of the bladder were entered in a prospective randomized trial to compare survival between a control group of 60 patients treated only with radical cystectomy (arm A) and a group of 62 patients treated with 3 cycles of 100 mg./m.2 neoadjuvant cisplatin before radical cystectomy (arm B). Secondary objectives of the trial were comparison of the disease-free interval and time to death, significance of response of the primary tumor to cisplatin, pattern of relapse and toxicity. As of April 1993 after a median followup of 78.2 months (range 48 to 101) no difference in survival between the control patients and those who received neoadjuvant cisplatin has been observed. The overall direct survival is 37.3% for arm A and 35.5% for arm B. The survival rate of the 109 patients who complied with the protocol is 38.2% for 55 patients of the control group and 40.7% for 54 patients of the cisplatin group. Survival rates of patients theoretically rendered free of disease by radical cystectomy (complete response pT0-4a, pN0-2, M0) is 43.7% for 40 control patients and 47.8% for 41 cisplatin treated patients. The time to relapse in complete response patients was significantly longer (p = 0.0298) for those who received cisplatin (arm A 13.1 months versus arm B 30.3 months). The time to death (cause specific) did not differ significantly between both groups overall (p = 0.1349) but it was significantly different between controls and responders (p = 0.0501). Preoperative cisplatin downstaged the primary tumor in 19 patients (33.9%), of whom 11 (19.6%) had no tumor in the cystectomy specimen (pT0) and 8 (14.3%) had superficial tumor (pTis pTa pT1). In 6 patients (9.7%) disease progressed during chemotherapy. The survival of the responders was significantly better than that of nonresponders (p = 0.0142), with specific death rate of 26.3% and 62.5%, respectively, and a median time to death of 43 months for responders and 30.5 months for nonresponders. Patients without nodal involvement (pN0) or with only 1 micrometastasis (pN1) fared significantly better (p = 0.0001) than those with major node invasion (pN2-4), irrespective of the treatment received. The survival rate is 48.6% for patients with pN0 disease, 37.5% for pN1 and 5% for pN2-4. Toxicity of cisplatin was minimal and there were no differences in perioperative morbidity between the arms.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗

PubMed1994

HIV infection presenting as renal polyarteritis nodosa.

We present a case of renal vasculitis (polyarteritis nodosa) in a 36-year-old female prostitute having undetected HIV infection (AIDS-related complex) and chronic B-hepatitis. The pathogenesis and significance of the association between these entities are reviewed.

AIDS-Related Opportunistic Infections↗

PubMed1994

Pseudosarcomatous myofibroblastic proliferation of the bladder: report of 2 cases and literature review.

We report 2 cases of pseudosarcomatous myofibroblastic proliferations of the bladder unrelated to urological trauma. To our knowledge, these cases represent the longest followup (12 and 19 years, respectively) reported in the literature, which confirms the long-term benign nature of an entity that may be clinically and even pathologically mistaken as malignancy. A review of the literature revealed a female predominance (3:1), 50% of the cases manifested in the first 2 decades of life and mean age was significantly lower in male patients (p < 0.005). These facts suggest the existence of a hormonal factor in the pathogenesis of this entity. A predilection for fundus, and the posterior and lateral walls also is demonstrated. In light of the complex embryogenesis of the cloacal territory, it could be hypothesized that this lesion arises from embryonal mesenchymal remnants of the endodermally derived urinary tract.

Adolescent↗

PubMed1994

Small cell carcinoma of the urinary bladder. A clinicopathological study of six cases.

OBJECTIVE: To study the clinical, histological, and immunohistochemical findings of small cell carcinoma (SCC) of the urinary bladder, and also to delineate its behaviour in comparison with transitional cell carcinomas of the bladder. MATERIALS AND METHODS: A retrospective review of 552 patients with bladder cancer yielded six cases (1%) of small cell carcinoma which were histologically identical to pulmonary small cell anaplastic carcinoma. Clinical data and follow-up were collected. Aside from the conventional histological parameters, an immunohistochemical study with AE1-AE3 and Cam 5.2 keratins, epithelial membrane antigen, neuron-specific enolase, chromogranin, synaptophysin, ACTH, calcitonin, and prostatic specific antigen was performed. RESULTS: The clinical presentation did not differ from conventional transitional cell carcinoma, haematuria being the most frequent complaint (four cases). All the cases presented as flat tumours. On light microscopy, there were oat cell (four cases), intermediate (one case) and mixed oat-cell/intermediate (one case) variants. Three cases were associated with transitional cell carcinoma. Dysplastic changes were observed in the adjacent urothelium in one case only. At the time of diagnosis, all tumours were deeply invasive (pT3). Three cases were Stage III and three Stage IV, with involvement of regional lymph nodes and metastases to the liver (two cases) and lung (one case). Immunohistochemically, epithelial markers were variably expressed as AE1-AE3 keratin (5/6), Cam 5.2 keratin (2/6) and epithelial membrane antigen (3/6). Neuron specific enolase was demonstrated in every case. Chromogranin, however, was expressed in only one case. Synaptophysin, ACTH, calcitonin, and prostatic specific antigen all gave negative results. All the patients died of the disease and the overall length of survival was very poor (range 5-25 months, mean 13.3). CONCLUSION: Small cell carcinomas show the same histological patterns as their pulmonary counterpart. Immunohistochemistry reveals a wide spectrum of activity, enolase and keratins being the most constant. The present study confirms that the overall prognosis of this tumour is very poor.

Aged↗

PubMed1994

Extrarenal retroperitoneal angiomyolipoma.

The clinical and pathological findings in a patient with extrarenal angiomyolipoma arising in the perinephric space are presented. This location has been reported only rarely and sets forth some diagnostic and therapeutic difficulties that are also discussed.

Angiomyolipoma↗

PubMed1994

Lethal cytomegalovirus adrenalitis in a case of AIDS.

The clinico-pathologic report of a case of cytomegalovirus (CMV) necrotizing adrenalitis arising in an intravenous drug-abuser and HIV-infected young is presented. CMV urinary tract infection, genital Kaposi's, and demyelinating changes in central nervous system were associated findings.

AIDS-Related Opportunistic Infections↗

PubMed1994

[Lateral cysts of the prostate].

Description and differential diagnosis of lateral cysts of the prostate gland which during their growth may invade its central section. Most cases, sized below 0.8 cm, are diagnosed by accident. A symptomatic prostate cyst is, in fact, a very uncommon condition. Presentation of one case of prostate cystadenoma which presented as a low urinary obstruction in a middle-age adult subject.

Adult↗

PubMed1993

Urinoma formation secondary to ureteral obstruction by metastatic squamous cell carcinoma of the appendix. Case report.

We report a case of secondary squamous cell carcinoma of the appendix causing spontaneous extravasation of urine and urinoma formation. On the basis of clinical findings, we interpret this rare lesion as metastatic from a cervical carcinoma surgically resected 8 years earlier. Ureteral continuity was restored by retrograde catheterization and the urinoma was drained percutaneously. The final diagnosis was made at laparotomy.

Aged↗

PubMed1993

Cavitation of lung metastases from bladder cancer. Report of two cases.

We describe 2 cases of cavitary lung metastasis from bladder cancer and retrospectively analyze the frequency of such an event in our environment. Although rare, this finding is not exceptional and should be taken into account when clinicians and oncologists face the differential diagnosis of pulmonary cavitation. Moreover, a cavitary pulmonary nodule may also be the presenting sign of bladder cancer.

Aged↗