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Biomedical subjects

S Ogden

Publications and source records attributed to S Ogden.

At least 19 recordsLinked to original sources
PubMed1997

Evaluating Children in the Ukraine for Colonization With the Intestinal Bacterium Oxalobacter formigenes, Using a Polymerase Chain Reaction-based Detection System.

Background: Oxalobacter formigenes is a recently discovered anaerobic bacterium residing in the gastrointestinal tracts of most vertebrates, including humans. Evidence suggests that this bacterium plays an important symbiotic relationship with its hosts by regulating oxalic acid homeostasis. Oxalic acid is a ubiquitous toxic by-product of metabolism associated with numerous pathologic conditions, including hyperoxaluia, cardiac myopathy and conductance disorders, kidney stones, and even death. Despite the potential importance of O. formigenes in several major health disorders, the difficulty in culturing, isolating, and identifying this fastidious anaerobe has limited research of its disease associations. Because O. formigenes must use two unique enzymes to catabolize oxalic acid, this bacterium appeared to be a suitable model for DNA-based identification, thereby circumventing the labor-intensive procedures currently used. Methods and Results: In this study, genus- and group-specific oligonucleotide sequences were designed corresponding to homologous regions residing in the oxc gene that enodes for oxalyl-coenzyme A decarboxylase. A polymerase chain reaction (PCR)-based amplification of the 5'end of this gene directly from genomic DNA isolated from various strains of O. formigenes was used to show that the genus- and group-specific oligonucleotide probes could identify and subgroup the bacterium. Field testing of this PCR-based detection system with 100 fecal cultures collected from children aged 0-12 years demonstrated the ease and efficacy with which O. formigenes can now be identified. Furthermore, these latter data provide a profile for the natural colonization of a human population with this intestinal bacterium. Conclusions: Development and use of this PCR-based detection system permit the rapid identification and classification of the gut-associated bacterium O. formigenes, thereby circumventing the need for the more labor-intensive and lengthy method currently used. The first field test of this detection system indicates that humans apparently do not become colonized with O. formigenes until they begin crawling about in the environment. Furthermore, studies investigating the association between several disorders (eg, kidney stones, irritable bowel syndrome, and hyperoxaluria) and the absence of the bacterium from the gut will now prove far easier.

Journal Article↗
PubMed1995

Impact of time delay, observational learning, and attentional cuing upon word recognition during integrated small-group instruction.

The effects of constant time delay, observational learning opportunities, and differential attentional cuing were examined during the small-group instruction of students in an integrated setting. Three students, one individual with moderate mental retardation and two individuals characterized as at-risk learners, participated in learning sight words through direct instruction and observational-learning conditions. A multiple probe design across three students was combined with a multitreatment design across treatment conditions to assess the impact of instructional variables. Reliability of scoring and procedural integrity were estimated and social validity of outcomes was considered. Findings support the salience of the constant time delay procedure in facilitating word acquisition in small, heterogeneous, and inclusive group learning arrangements. Further, a significant amount of learning through observation occurred for all students under both a general and specific attentional cue condition. A slight but discernible advantage of using the specific cuing strategy of transcribing target and nontarget words was realized.

Attention↗
PubMed1991

Circadian infusion of floxuridine in patients with metastatic renal cell carcinoma.

A total of 42 patients with metastatic renal cell carcinoma received floxuridine infusion for 14 days at monthly intervals. The drug was delivered via an external programmable pump on a time-modified or circadian schedule; the highest dose of 68% was given between 3 and 9 p.m. Of the 42 patients 25 (60%) had undergone prior nephrectomy. Of the 40 evaluable patients 4 (10%, 95% confidential interval 3 to 24%) achieved a partial response: 3 of the 4 had undergone prior nephrectomy, while 1 had undergone renal angioinfarction. Another 4 patients (10%) had responses at metastatic sites but no response in the primary kidney tumor. The median duration of response for these 2 groups of patients was 65 and 27 weeks, respectively, and the most responsive site was the lungs. The treatment was generally well tolerated and could be administered on an outpatient basis. Our study confirms the limited but definite activity of floxuridine infused on a circadian schedule in patients with metastatic renal cell carcinoma. We observed responses in metastasis equally in patients with or without prior nephrectomy.

Adult↗
PubMed1989

Advantages of firefly luciferase as a reporter gene: application to the interleukin-2 gene promoter.

The chloramphenicol acetyltransferase (CAT) gene is widely used in recombinant constructs employed to study promoter and enhancer control of gene expression. However, CAT-based assays require a laborious, multi-step procedure for quantitation of promoter activity. We have applied the recently described firefly luciferase (LUC) reporter gene to the study of the interleukin-2 (IL2) promoter and have further defined the properties of this reporter gene system. We find that IL2-LUC constructs have multiple advantages over IL2-CAT constructs. The LUC assay is highly sensitive and requires 1/10 the cells used in the CAT system. A final quantitative measure of promoter activity can be obtained within 25 h following transfection with IL2-LUC, compared to 108-160 h with IL2-CAT. Light emission significantly (fourfold) above background is detectable 3 h after induction in a direct assay of extracts from transfected cells. We have described the variability of the assay, the minimum number of transfected cells required to detect light, the stability of luciferase in cell extracts, the effect of Triton X-100 on the assay, and a rapid cell lysis procedure. The luciferase system is a simple, rapid, and sensitive method for the study of promoter activity in transfected cells, particularly for weakly expressed genes such as IL2 which give low activity in the CAT assay.

Animals↗
PubMed1989

Clinical and radiological correlation of retroperitoneal metastasis from nonseminomatous testicular cancer treated with chemotherapy.

Forty patients with retroperitoneal metastasis from nonseminomatous testicular cancer treated with chemotherapy were retrospectively studied to (1) evaluate the predictive value of mass size as detected by computerized tomography (CT) as an indicator for postchemotherapy surgery and (2) determine the factors that influence relapse. Patients received two further courses of chemotherapy after their serum biomarkers became normal and computed tomography indicated a complete response or presence of a residual but stable mass. We found that patients with initial metastases less than 2 cm had a low frequency (14%) of residual masses after chemotherapy, vs. 59% for those with masses of 2-5 cm and 75% for those with masses of greater than 5 cm (P = 0.03). Of 22 patients with primary embryonal carcinoma, three of seven (43%) with residual masses after chemotherapy had mature teratoma at surgery. Six patients had small (1-2 cm) residual abnormalities that were not removed, and three of these patients relapsed. In conclusion, increasing size of retroperitoneal metastasis by CT scan predicts for increased likelihood of a residual mass after chemotherapy; patients who have a residual mass greater than or equal to 1 cm require retroperitoneal lymphadenectomy after chemotherapy, whether the tumor histology is embryonal carcinoma or teratoma. The role of surgery for patients who have residual retroperitoneal masses less than 1 cm after chemotherapy could not be determined from our study.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Localization of preferential sites of rearrangement within the BCR gene in Philadelphia chromosome-positive acute lymphoblastic leukemia.

The Philadelphia chromosome associated with acute lymphoblastic leukemia (ALL) has been linked to a hybrid BCR/ABL protein product that differs from that found in chronic myelogenous leukemia. This implies that the molecular structures of the two chromosomal translocations also differ. Localization of translocation breakpoints in Philadelphia chromosome-positive ALL has been impeded due to the only partial characterization of the BCR locus. We have isolated the entire 130-kilobase BCR genomic locus from a human cosmid library. A series of five single-copy genomic probes from the 70-kilobase first intron of BCR were used to localize rearrangements in 8 of 10 Philadelphia chromosome-positive ALLs. We have demonstrated that these breakpoints are all located at the 3' end of the intron around an unusual restriction fragment length polymorphism caused by deletion of a 1-kilobase fragment containing Alu family reiterated sequences. This clustering is unexpected in light of previous theories of rearrangement in Philadelphia chromosome-positive chronic myelogenous leukemia that would have predicted a random dispersion of breakpoints in the first intron in Philadelphia chromosome-positive ALL. The proximity of the translocation breakpoints to this constitutive deletion may indicate shared mechanisms of rearrangement or that such polymorphisms mark areas of the genome prone to recombination.

Base Sequence↗
PubMed1988

The order and orientation of mouse lambda-genes explain lambda-rearrangement patterns.

Mouse lambda-genes are rearranged in specific V lambda-JC lambda associations: V lambda 1 has only been found to rearrange with JC lambda 3 or JC lambda 1, whereas V lambda 2 mainly rearranges with JC lambda 2 and very rarely with JC lambda 1,3. In order to determine the physical basis for these associations we have cloned the respective lambda-genes and large portions of their flanking regions by chromosomal walking in a total of 141 kb of phage and cosmid clones. With the use of unique probes obtained from such clones, the order and orientation of the mouse lambda-gene segments were determined by analyzing patterns of DNA deletion associated with lambda-gene rearrangements in various cell lines. All V and C gene segments were found to be in the same transcriptional orientation, and V2 and V1 were found not to be next to each other, thus supporting the gene order V2-C2-C4-V1-C3-C1.

Animals↗
PubMed1988

Genetic abnormalities in men with germ cell tumors.

We retrospectively reviewed the genetic abnormalities detected clinically in 455 men with advanced germ cell tumors referred for chemotherapy. Of the patients 49 had extragonadal and 406 had testicular germ cell tumors. Of 19 patients with mediastinal germ cell tumors 4 (21 per cent, 3 with teratocarcinoma and 1 with endodermal sinus tumor) had Klinefelter's syndrome. Three of these patients had a 47XXY and 1 had a 48XXYY karyotype. No Klinefelter's syndrome was observed among 30 consecutive patients with retroperitoneal germ cell tumors or among the 406 with testicular tumors. Karyotypes of 35 consecutive patients with testis cancer without evident congenital abnormalities showed normal chromosomal patterns. We found 2 patients with Down's syndrome and testicular tumor, for an incidence of 0.5 per cent (probably significant). We also describe 2 cases of nonseminomatous testicular cancer and Marfan's syndrome (0.5 per cent incidence versus a 5 of 100,000 incidence of Marfan's syndrome in the general population). Apparently, genetic abnormalities are increased in men with germ cell tumors and we discuss the significance of this association.

Adolescent↗
PubMed1988

Adjuvant chemotherapy of bladder cancer: a preliminary report.

Adjuvant combination chemotherapy with cyclophosphamide, doxorubicin and cisplatin was administered to 36 patients after cystectomy for bladder cancer. Therapy was tolerated well except for 1 patient who suffered a fatal chemotherapy complication. Indications for adjuvant chemotherapy included vascular invasion of the primary tumor, perivesicular tumor involvement, invasion of adjacent pelvic viscera (vagina and prostate) and nodal metastases. There were 53 concurrently treated patients who did not receive adjuvant chemotherapy despite similar unfavorable pathological indications (high risk control group). Survival rates (61 and 73 per cent, respectively) were not significantly different for those patients treated with adjuvant chemotherapy and an additional group of 158 patients who underwent cystectomy during the study period but who had no adverse pathological findings (low risk control group). Survival rates differed significantly between the low risk (73 per cent) and high risk (38 per cent) control groups (p less than 0.001). Patients with unfavorable histological findings who received adjuvant chemotherapy had a significant survival advantage over the high risk control groups (61 versus 38 per cent, p equals 0.03). These data confirm the predictive value of post-cystectomy pathological findings and suggest that adjuvant chemotherapy with cyclophosphamide, doxorubicin and cisplatin not only prolongs the survival free of disease for patients at high risk for recurrence but it also may ultimately increase the cure fraction of such patients.

Adult↗
PubMed1988

Adjuvant cyclophosphamide, doxorubicin, and cisplatin chemotherapy for bladder cancer: an update.

Seventy-one patients received adjuvant Cytoxan (cyclophosphamide; Bristol-Myers Co, Evansville, IN), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (CISCA) chemotherapy between March 1981 and March 1986. Patients received adjuvant CISCA chemotherapy if they had pathological findings that were thought to predict for high likelihood of relapse. These included the presence of resected nodal metastases, extravesicular involvement of tumor, lymphatic/vascular permeation of the primary tumor, or pelvic visceral invasion. Sixty-two patients at a similar high risk for recurrence did not receive adjuvant CISCA chemotherapy because they refused, had medical contraindications to therapy, or were not referred for chemotherapy. Two-hundred six patients had a cystectomy performed during the same study period but had none of the poor prognostic features suggesting a high risk for relapse. Sixty-two percent of the patients receiving adjuvant chemotherapy are alive and disease-free for a mean follow-up of 118 weeks (range, 28 to 310 weeks). A survival advantage exists for the adjuvant-treated patients when compared with those with unfavorable pathological findings who did not receive adjuvant chemotherapy (70% v 37%) (P = .00012): no difference exists in long-term disease-free survival for those with favorable pathological findings (long-term disease-free survival 76%) v those who received adjuvant chemotherapy (70%) (P = .33). Adjuvant CISCA chemotherapy prolongs the disease-free survival of some patients following a cystectomy. Patients who benefitted from adjuvant CISCA chemotherapy included those with resected nodal metastases, extra-vesicular involvement of tumor, and direct invasion of the pelvic viscera. Patients not benefitting from adjuvant CISCA chemotherapy in this analysis included those with lymphatic/vascular invasion in their primary tumor as the sole manifestation of high risk for relapse.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Primary chemotherapy for clinical stage II nonseminomatous germ cell tumors of the testis: a follow-up of 50 patients.

Fifty patients with clinical stage II nonseminomatous germ cell tumor of the testis (NSGCTT) were treated with primary chemotherapy followed by a retroperitoneal lymph node dissection (RPLND) in selected patients. The study population included 34 patients with retroperitoneal masses and elevated levels of serum biomarkers (alpha-fetoprotein [AFP] and beta-human chorionic gonadotropin [BHCG] ), five with needle aspiration biopsy-proven retroperitoneal metastases but normal levels of biomarkers, and 11 in whom there were rising levels of serum biomarkers but no radiographic evidence of retroperitoneal metastases. Forty-eight patients (96%) achieved a complete response (CR), with a mean disease-free survival of 132 weeks (range, 55 to 273 weeks). Two patients developed recurrent disease. One died and one achieved a second CR with further therapy (48 + weeks). Postchemotherapy RPLND was required in 11 patients (22%). Patients with embryonal carcinoma had a lower frequency of RPLND (8%) than patients with teratomatous elements in their primary tumor [36%, P = .014]. To reduce the frequency of double therapy (surgery +/- chemotherapy), we propose individualized therapy. Patients presenting with clinical stage II embryonal carcinoma of the testis should receive primary chemotherapy. Patients with clinical stage II NSGCTT and teratomatous elements in their primary tumor continue to require an RPLND. Those patients with intermediate volume disease (greater than 2 cm less than or equal to 5 cm in maximum diameter) may be treated with an RPLND only. Patients with higher volume teratomatous elements (greater than 5 cm less than or equal to 10 cm in maximum diameter) are likely to require the combination of chemotherapy and surgery.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Cyclic chemotherapy with cyclophosphamide, doxorubicin, and cisplatin plus vinblastine and bleomycin in advanced germinal tumors. Results with 100 patients.

One hundred patients with advanced mixed germ-cell tumors were treated with cisplatin, cyclophosphamide, and doxorubicin alternating with vinblastine and bleomycin (cyclic CISCAII/VBIV). The chemotherapy achieved an 89 percent continuous disease-free status (85 percent with chemotherapy, 4 percent with chemotherapy plus surgery). The mean follow-up duration for patients with continuous complete remission was 132 weeks (+/- 6.2), with a median of 126 weeks. Multivariate analysis using a stepwise logistic regression of prognostic variables revealed that a high serum level of the beta subunit of human chorionic gonadotropin (more than 50,000 mIU/ml) was of prognostic significance, followed by the Samuels staging criteria and extragonadal origin of disease. Thirty-two patients underwent exploratory surgery after they had had two courses of chemotherapy beyond the establishment of a stable mass and absent serum biomarkers. No viable cancer was found at exploration, and all patients remain alive and free of disease. The acute toxicity of the cyclic chemotherapy was formidable, but only one patient had a fatal complication. Thirty-six percent of the CISCAII courses and 44 percent of the VBIV courses were associated with leukopenic fever, and 5 percent of the CISCAII courses and 8 percent of the VBIV courses were associated with culture-positive infection. Long-term toxicity was unusual: bleomycin lung toxicity 1 percent, cardiac toxicity 1 percent. CISCAII/VBIV cyclic chemotherapy is superior to cisplatin, vinblastine, and bleomycin (PVB) chemotherapy; it results in a higher complete remission rate, a lower relapse rate, and a lower incidence of long-term complications. Patients with a high risk of failure of PVB chemotherapy (Samuels stage IIIB3 to IIIB5) or with extragonadal tumors should be treated with CISCAII/VBIV.

Adolescent↗
PubMed1985

Chemotherapy for adenocarcinomas of bladder and urachal origin: 5-fluorouracil, doxorubicin, and mitomycin-C.

Eight patients with unresectable adenocarcinoma of the bladder or urachus were treated with chemotherapy. Four had received cisplatin-based chemotherapy (CISCA), all 4 failed to respond. All 8 received intravenous and/or intra-arterial 5-fluorouracil, doxorubicin hydrochloride (Adriamycin), and mitomycin-C. Three of the 5 responding patients had short responses while 2 had achieved long-term control of disease. One is in complete remission for eleven plus months, and 1 patient had a partial remission of nineteen plus months. Five patients had serum CEA levels measured at presentation. In the 3 patients with an elevated CEA at presentation who responded to chemotherapy a corresponding drop in the initial level was seen. 5-Fluorouracil-based chemotherapy is effective in the management of adenocarcinoma of the bladder.

Adenocarcinoma↗
PubMed1985

Cyclophosphamide, doxorubicin and cisplatin chemotherapy for patients with locally advanced urothelial tumors with or without nodal metastases.

Thirty-eight patients with primary urothelial tumors recurring in the pelvis or nodal presentation were treated with intravenous or intra-arterial cyclophosphamide, doxorubicin and cisplatin chemotherapy. The 38 patients were selected owing to unresectability by local criteria (12 patients) or by virtue of nodal metastases (26 patients). Histologically, the patients either had pure transitional cell carcinoma (29), transformation to a histological subtype of transitional cell carcinoma (7) or pure squamous cell carcinoma (2). An over-all 50 per cent complete remission rate was achieved with an 18 per cent objective pelvic response rate, and 32 per cent failed to respond to chemotherapy. Responses by histological subtype revealed that patients with pure transitional cell carcinoma had a 62 per cent complete remission rate, those with transitional forms had a 14 per cent complete remission rate and none with squamous cell carcinoma responded to chemotherapy. A significant difference in the incidence of responses among patients with transitional carcinoma and those with transition forms was seen (p less than 0.02). Complete remissions were independent of disease site. Nineteen patients achieved a complete remission with a mean duration of 86 weeks and median of 81 weeks (range 33 to 172 weeks). Toxicity of the chemotherapy was moderate with a high incidence of peripheral neuropathy and leukopenic infections. No deaths of chemotherapy were encountered. Patients with locally advanced or metastatic transitional cell carcinoma of the urothelium to lymph nodes can benefit from intravenous and intra-arterial cyclophosphamide, doxorubicin and cisplatin chemotherapy.

Adult↗
PubMed1984

An operator at -280 base pairs that is required for repression of araBAD operon promoter: addition of DNA helical turns between the operator and promoter cyclically hinders repression.

A site has been found that is required for repression of the Escherichia coli araBAD operon. This site was detected by the in vivo properties of deletion mutants. In vitro protection studies with DNase I and dimethylsulfate showed that araC protein can specifically bind in this area to nucleotides lying at position -265 to -294 with respect to the araBAD operon promoter (PBAD) transcription start point. The previously known sites of protein binding in the ara operon lie between +20 and -160. Since the properties of deletion strains show that all the sites required for araBAD induction lie between +20 and -110, the new site at -280 exerts its repressive action over an unusually large distance along the DNA. Insertions of -16, -8, 0, 5, 11, 15, 24, and 31 base pairs of DNA between the new site and PBAD were constructed. Repression was impaired in those cases in which half-integral turns of the DNA helix were introduced, but repression was nearly normal for the insertions of 0, +11, and +31 base pairs.

AraC Transcription Factor↗
PubMed1983

Doxorubicin, mitomycin-C, and 5-fluorouracil (DMF) in the treatment of metastatic hormonal refractory adenocarcinoma of the prostate, with a note on the staging of metastatic prostate cancer.

Sixty-two patients with metastatic hormonal refractory adenocarcinoma of the prostate received a combination of doxorubicin, mitomycin-C, and 5-fluorouracil (DMF). Thirty (48%) of the patients achieved an objective response. Response criteria excluded disease "stabilization" as a manifestation of response. Four clinical prognostic categories were identified: osseous I (OI) had metastatic axial skeletal involvement (23 patients); osseous II (OII) had axial and extremity skeletaL involvement (18 patients); visceral I (VI) had pulmonary metastasis (9 patients); and visceral II (VII) had pulmonary metastasis and involvement of other viscera (12 patients). The 20 responding patients survived a median of 47.5 weeks, whereas the 32 nonresponding patients survived a median of 23.8 weeks (n = 0.002). Response rates were highest among patients with OI (52%) and VI (88%) disease; response rates were lower amont patients with OII (33%) and VII (33%) disease. Responding patients in each clinical category survived longer than nonresponding patients except for those patients with VII disease. The median duration of response for patients with OI disease was 11 months, for OII 9.5 months, for VI patients it was 6.5 months, and VII patients it was 5 months. DMF is an effective treatment of metastatic hormonal refractory prostate cancer, resulting in consistent objective responses. The staging system employed identifies four clinical categories of metastatic prostate cancer and allows for accurate comparison of diet and stratification of study populations.

Adenocarcinoma↗