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Biomedical subjects

B Bochner

Publications and source records attributed to B Bochner.

12 recordsLinked to original sources

Limits on gravitational-wave emission from selected pulsars using LIGO data.

We place direct upper limits on the amplitude of gravitational waves from 28 isolated radio pulsars by a coherent multidetector analysis of the data collected during the second science run of the LIGO interferometric detectors. These are the first direct upper limits for 26 of the 28 pulsars. We use coordinated radio observations for the first time to build radio-guided phase templates for the expected gravitational-wave signals. The unprecedented sensitivity of the detectors allows us to set strain upper limits as low as a few times 10(-24). These strain limits translate into limits on the equatorial ellipticities of the pulsars, which are smaller than 10(-5) for the four closest pulsars.

Journal Article↗

Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients.

PURPOSE: To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes. PATIENTS AND METHODS: All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients. RESULTS: A total of 1,054 patients (843 men [80%] and 211 women) with a median age of 66 years (range, 22 to 93 years) were uniformly treated. Median follow-up was 10.2 years (range, 0 to 28 years). There were 27 (2.5%) perioperative deaths, with a total of 292 (28%) early complications. Overall recurrence-free survival at 5 and 10 years for the entire cohort was 68% and 66%, respectively. The 5- and 10-year recurrence-free survival for patients with organ-confined, lymph node-negative tumors was 92% and 86% for P0 disease, 91% and 89% for Pis, 79% and 74% for Pa, and 83% and 78% for P1 tumors, respectively. Patients with muscle invasive (P2 and P3a), lymph node-negative tumors had 89% and 87% and 78% and 76% 5- and 10-year recurrence-free survival, respectively. Patients with nonorgan-confined (P3b, P4), lymph node-negative tumors demonstrated a significantly higher probability of recurrence compared with those with organ-confined bladder cancers (P <.001). The 5- and 10-year recurrence-free survival for P3b tumors was 62% and 61%, and for P4 tumors was 50% and 45%, respectively. A total of 246 patients (24%) had lymph node tumor involvement. The 5- and 10-year recurrence-free survival for these patients was 35%, and 34%, respectively, which was significantly lower than for patients without lymph node involvement (P <.001). Patients could also be stratified by the number of lymph nodes involved and by the extent of the primary bladder tumor (p stage). Patients with fewer than five positive lymph nodes, and whose p stage was organ-confined had significantly improved survival rates. Bladder cancer recurred in 311 patients (30%). The median time to recurrence among those patients in whom the cancer recurred was 12 months (range, 0.04 to 11.1 years). In 234 patients (22%) there was a distant recurrence, and in 77 patients (7%) there was a local (pelvic) recurrence. CONCLUSION: These data from a large group of patients support the aggressive surgical management of invasive bladder cancer. Excellent long-term survival can be achieved with a low incidence of pelvic recurrence.

Adult↗

Adjuvant radiotherapy in patients with pathologic Stage C (pT3N0) adenocarcinoma of the prostate.

OBJECTIVES: This report is an update on the outcomes in the management of pathologic Stage C (T3N0) prostate cancer (CaP) with postoperative irradiation. METHODS: Between 1976 and 1994, 311 patients with pathologic Stage C CaP were treated with radical prostatectomy. Pathologic stage was as follows: C1, 60 patients (19%), C2, 146 patients (47%), and C3, 105 patients (34%). Gleason score was 2 to 4 in 10 patients (3.2%), 5 to 6 in 121 (39%), 7 in 101 (32%), and 8 to 10 in 76 (24%); median prostate-specific antigen (PSA) level was 11.9 ng/mL. Postoperative irradiation consisted of a median dose of 48 Gy. Follow-up was up to 18 years (median 5). RESULTS: The 10-year actuarial survival was 81% and 10-year disease-free survival was 51%. Pathologic stage and Gleason score were independently predictive of recurrence, each with P >0.001 after controlling for the other. Patients with pathologic Stage C3 and Gleason score 7 to 10 were in the worst prognostic category and had 5.4 times the risk of recurrence compared with patients with pathologic Stage C1-C2, Gleason score 2 to 6. Preoperative PSA was a good (P = 0.02) predictor of disease-free survival. Clinical recurrence was seen in 28 patients (9%), including 10 (3.2%) with local recurrence. PSA recurrence (PSA greater than 0.05 ng/mL) developed in 68 patients (22%). CONCLUSIONS: With the known limitations of a nonrandomized clinical trial, on the basis of the experience of this study we recommend the use of moderate dose, limited-field postoperative radiotherapy in patients with pathologic Stage C disease with Gleason score greater than 4.

Actuarial Analysis↗

Comparison of outcomes of radical prostatectomy with and without adjuvant pelvic irradiation in patients with pathologic stage C (T3N0) adenocarcinoma of the prostate.

Patients with localized adenocarcinoma of the prostate gland (CaP) are frequently (approximately 50%) found at radical prostatectomy to have extracapsular disease or positive surgical margins. The management of these patients is a subject of controversy because some question the impact of this manifestation of CaP on patient survival or disease-free survival. Between 1976 and 1991, 241 patients with pathologic stage C (T3N0) were treated in this medical center. Of these 241 patients, 201 (83%) received a planned postoperative pelvic irradiation consisting of 48 Gy given to the prostatic fossa, whereas 40 (17%) patients were treated with radical prostatectomy alone. The two study urologists selected these patients not to receive postoperative irradiation based on intraoperative findings and important prognostic factors. Comparison of treatment outcomes in these two treatment groups is a subject of this report. The 201 patients treated with surgery-radiotherapy (S+RT) combination had a higher pathologic stage, greater incidence of seminal vesicle involvement, p = 0.002, and higher mean and median preoperative prostate-specific antigen level, p < 0.0001, than the 40 surgery (S) alone patients. There was no significant difference in the incidence of higher Gleason's score by the treatment group, p = 0.14. In univariate analysis, there was no significant difference in survival, disease-free survival, and time to failure between the two treatment groups. In multivariate analysis after controlling for pathologic stage and Gleason's score, the 201 adjuvant radiotherapy patients were predicted to have recurrence at 68% (95% confidence interval 39%-118%) the rate of the 40 surgery-alone patients. Local recurrence with or without metastatic disease was found in 10% of surgery-alone patients as compared to 5% in those also receiving postoperative irradiation. Treatment tolerance was very good with minor radiotherapy complications only. There was no significant difference in the incidence of incontinence between the two treatment arms. In summary: (a) The use of moderate-dose postoperative radiotherapy was of low toxicity and it did not increase the incidence of incontinence. (b) Local recurrence was 5% in S+RT and 10% in S-alone patients. (c) In multivariate analysis, S+RT patients had 68% rate of recurrence of S-alone patients. (d) Adjuvant RT probably reduces the risk of recurrence in patients with poor prognostic factors. (e) These data need to be interpreted with caution because of the nonrandomized nature of the study.

Adenocarcinoma↗

Novel bacterium isolated from a lung transplant patient with cystic fibrosis.

The major clinical problem for patients with cystic fibrosis (CF) is progressive loss of pulmonary function, usually due to chronic bacterial infections. A patient with CF and a lung transplant was severely infected with a previously unidentified gram-negative bacterium. We isolated this organism (strain DS15158) from the patient and characterized it by phylogenetic analysis of the small-subunit rRNA and biochemically by the BIOLOG GN MicroPlate assay, fatty acid analysis, and various standard laboratory tests. No close match to any other organism could be found. Isolate DS15158 represents a new genus-level divergence within the bacterial subdivision alpha-Proteobacteria on the basis of the 16S rRNA gene analysis.

Adult↗

Immunolocalization of CD34 in nasal polyposis. Effect of topical corticosteroids.

Airway inflammation in patients with nasal polyps is characterized by the increased presence of eosinophils, the numbers of which are reduced after treatment with topical corticosteroids. Because eosinophilic responses in the airways are in part due to eosinophil progenitor differentiation, we hypothesized that CD34, a cell surface, sialomucinlike glycoprotein that specifically marks hemopoietic progenitors and endothelium, would be expressed in nasal polyp tissue. We sought to identify CD34(+) leukocytes or endothelial cells in nasal polyps. We also investigated the effect of the topical corticosteroid budesonide on the numbers of CD34(+) cells and vessels in nasal polyps. To accomplish this, we performed immunostaining for CD34 protein in tissue sections of nasal polyps from topical steroid-treated and -untreated groups of patients, as well as from one patient before and after systemic corticosteroid therapy. We also examined myeloid colony formation by isolated polyp mononuclear cells, and performed flow cytometry to detect the presence of CD34(+)/CD45(+) cells within these isolated populations. We also examined the in vitro effects of steroids on human umbilical vein endothelial cell (HUVEC) expression of CD34. We detected CD34-immunoreactive mononuclear cells and blood vessels in the lamina propria of all nasal polyps. CD34(+) mononuclear cells resembled immature hemopoietic cells morphologically. Mononuclear cell fractions from polyps contained myeloid colony-forming cells and cells bearing CD45, a pan-leukocyte marker, as well as CD34, and gated as true hemopoietic blast cells. The numbers of CD34(+) cells and CD34(+) vessels in steroid-treated nasal polyps were significantly higher than in steroid-untreated nasal polyps (15.67 +/- 2.08 cells/10 hpf, versus 5.33 +/- 1.36 cells/10 hpf, P = 0.002; 101.25 +/- 6.24 vessels/0.5 mm2 of lamina propria, versus 57.22 +/- 8.00 vessels/0.5 mm2 of lamina propria, P = 0.0008, respectively). A similar upregulation of CD34 immunostaining, especially for mononuclear cells, was observed in one patient after systemic corticosteroid therapy. Steroid treatment in vitro of HUVECs did not result in enhanced CD34 expression. Both CD34(+)/CD45(+) mononuclear cells and CD34(+) endothelial cells are present within nasal polyps, with higher numbers in patients who have received topical corticosteroid treatment. Because enhancement of CD34 expression was not seen in cultured umbilical vein endothelial cells treated in vitro with corticosteroid, the findings of the study suggest that in nasal polyp tissue, steroids enhance numbers of CD34(+) progenitors and endothelial cells via indirect mechanisms.

Administration, Topical↗

Interleukin-6 and renal cell cancer: production, regulation, and growth effects.

Interleukin-6 (IL-6) is a recently characterized pleiotropic cytokine with antitumor activity. We investigated the production of IL-6 by renal cell cancer (RCC) and the growth effects of IL-6 on RCC. Using immunoperoxidase staining, cytoplasmic IL-6 was detected in four of four renal tumor lines and in tumor cells from freshly nephrectomized RCC. We found that IL-6 mRNA was expressed at basal culture conditions by seven of ten RCC tumor lines tested. Biologically active IL-6, as measured by the B9 assay, was produced by all ten RCC tumor lines. The addition of tumor necrosis factor alpha (TNF alpha) significantly augmented the expression of IL-6 mRNA in five RCC tumor lines (P less than 0.05). The combination of interferon gamma IFN gamma and TNF alpha further enhanced the augmented IL-6 mRNA accumulation seen with TNF alpha alone (P less than 0.05). TNF alpha also significantly stimulated the production of biologically active IL-6 (P less than 0.01). Furthermore, IFN gamma and TNF alpha were found to enhance IL-6 bioactivity synergistically (P less than 0.05). The growth effects of IL-6 on RCC were also investigated in two experimental systems: IL-6 was found to stimulate proliferative responses in six of six RCC tumor lines as measured by thymidine-uptake assays; however, only one of six tumor lines displayed an increase in proliferative response of greater than 21% (113%). The growth effect of IL-6 was further tested in clonogenic assays. One of the tumor lines tested displayed an enhanced growth response of up to 200%. We conclude that IL-6 is produced by RCC; this production is enhanced by TNF alpha with synergistic effects seen with IFN gamma at both mRNA and protein levels. In turn, IL-6 may have a modest stimulatory growth effect on certain RCC tumor lines.

Blotting, Northern↗

[Adoptive immunotherapy and metastasized cancer of the kidney. Regulator effects of interleukin-4 on tumor infiltrating lymphocytes (TIL)].

Adoptive immunotherapy is a new therapeutic approach of the treatment of advanced renal cell cancer. Experimental studies have shown that the cells with the highest cytolytic activity are tumor infiltrating lymphocytes (TIL). The effects of interleukin-4 (IL-4) on the expansion, proliferation, phenotype and antitumor activity of TIL were studied. Cultures were obtained from three primary renal tumors and one group of tumor invaded, regional lymph nodes. IL-4 induced a significant increase in lymphocytes expansion and proliferation, but the response was dependent of the concurrent dose of IL-2 in culture. TIL grown in the presence of IL-4 significantly reduced the level of non specific, non MHC restricted antitumor activity while exhibiting no effect on the level of autologous killing. The effects of irradiated autologous tumor stimulation on TIL cultures were also evaluated. Addition of autologous tumor increased expansion and proliferation of all cultures and significantly enhanced levels of autologous killing. IL-4 and autologous tumor stimulation are effective growth factors when used in combination with a lose dose IL-2 regimen and may be of significant benefit in the expansion of TIL for clinical trials.

Adenocarcinoma↗

High-level secretion of human growth hormone by Escherichia coli.

A gene encoding the mature form of human growth hormone (hGH) was fused to the secretion signal coding sequence of the Escherichia coli heat-stable enterotoxin II (STII). This hybrid gene was preceded by two Shine-Dalgarno sequences derived from the trp and STII-coding genes and was expressed in E. coli under the transcriptional control of the E. coli alkaline phosphatase (phoA) promoter. In low-phosphate growth media, cells synthesized about 15 to 25 micrograms of hGH/ml/1 A550 unit of cells. This represents 6 to 10% of total cellular protein. The majority of the hGH produced (more than 90%) was processed precisely and secreted into the periplasmic space. These results demonstrate that E. coli cells are able to synthesize and secrete high levels of this human protein using a prokaryotic signal sequence.

Chorionic Gonadotropin↗

Detection of DNA base damage by 32P-postlabelling: TLC separation of 5'-deoxynucleoside monophosphates.

Traces of damaged bases in DNA can be detected without the use of radioactive chemical agent or radiolabelled DNA substrate by incorporation of radiolabel into DNA after exposure to the chemical. This postlabelling approach to carcinogen adduct analysis is potentially useful for adduct detection in the DNA of humans exposed to carcinogens. We describe here the postlabelling analysis of DNA by chromatography of deoxynucleoside monophosphates. Separation and characterization of modified residues in nucleotide digests of DNA treated in vitro with chloroacetaldehyde is demonstrated.

Acetaldehyde↗