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Biomedical subjects

W Warren

Publications and source records attributed to W Warren.

At least 55 records · Page 3Linked to original sources
PubMed1990

Chemical induction of thymomas in AKR mice: interaction of chemical carcinogens and endogenous murine leukemia viruses. Comparison of N-methyl-N-nitrosourea and methyl methanesulphonate.

The time course of development of thymic lymphoma, which occurs spontaneously in mice of the AKR strain, is accelerated by the methylating agents N-methyl-N-nitrosourea (MNU) and methyl methanesulphonate (MMS). Since MNU is a potent mutagen inducing G----A transition mutations and MMS a relatively weak mutagen, it was of interest to examine the genetic alterations associated with each class of the chemically induced tumors and to compare these alterations with those found in the spontaneous tumors. The same spectrum of genetic alterations was found for MMS-induced and spontaneous thymomas. Both showed rearrangements of c-myc and Pim-1 genes that appeared to result from integration of recombinant mink cytopathic focus-forming (MCF) proviruses but failed to reveal evidence for activation of ras oncogenes, either by DNA transfection experiments or by hybridization of DNA to specific oligonucleotide probes. Some alteration in c-myc and Pim-1 genes were also found in MNU-induced tumors, but, mainly, these involved integration of ecotropic-like rather than recombinant MCF viruses. Furthermore, MNU-induced tumors frequently (in 24% of thymomas) contained G----A transition mutations, activating the Ki-ras oncogene at codon 12 position 2. Another feature that distinguishes the MNU-induced tumors from those occurring in untreated and MMS-treated mice was the consistently high level of c-myc mRNA that occurred in the absence of c-myc gene rearrangement. Taken together, the data indicate that the mechanisms of development of tumors following treatment with MNU and MMS are distinct, and that the effect of MMS is probably to speed up the process of viral leukemogenesis.

Animals↗
PubMed1990

Mutation of the p53 gene in human soft tissue sarcomas: association with abnormalities of the RB1 gene.

Soft tissue sarcomas have been examined for alterations in the p53 gene. In six sarcomas, loss or rearrangement of both alleles of this gene was detected while in a further seven sarcomas, point mutation or absence of transcription of the p53 gene was observed. Abnormalities of the p53 gene were found in several classes of soft tissue sarcoma, including leiomyosarcomas, rhabdomyosarcomas and malignant fibrous histiocytomas. Our studies also show that abnormalities of the RB1 suppressor gene and of the p53 gene frequently occur together. These results are consistent with the idea that the p53 gene is a tumour suppressor gene and indicate that coincident inactivation of more than one tumour suppressor gene may, in some cases, be required for tumour development.

Base Sequence↗
PubMed1990

Early detection of caudal regression syndrome with transvaginal scanning.

High-resolution transvaginal ultrasonography may recognize structures in the first- and early second-trimester fetus. In a patient with pregestational diabetes, caudal regression syndrome in the fetus was diagnosed using transvaginal ultrasonography. At 9 weeks of gestation, a shortening of the crown-rump length and a protuberance of the lower spine suggested caudal regression syndrome. By 17 weeks of gestation, the diagnosis was made with certainty. The transvaginal approach has changed the role of first-trimester ultrasound in the diabetic pregnancy. We suggest that transvaginal ultrasonography be used for purposes of accurate dating and for early detection of diabetic embryopathy, particularly in patients with poor periconceptional glycemic control.

Adult↗
PubMed1989

Absence of end-diastolic umbilical artery blood flow predicts poor fetal outcome despite normal blood gases.

A case is reported in which the fetal acid-base status was assessed by means of cordocentesis in a fetus without end-diastolic umbilical artery blood flow. The absence of end-diastolic flow was not associated with acidosis or hypoxia. However, the fetal condition deteriorated 3 days later, which suggests that even with a normal fetal acid-base status, an extended margin of safety cannot be assumed with the absence of end-diastolic umbilical flow.

Acid-Base Equilibrium↗
PubMed1989

Immunohistochemical analysis of pulmonary and pleural tumors with the monoclonal antibody HYB-612 directed against the multidrug resistance (MDR-1) gene product, P-glycoprotein.

In this study, 212 untreated primary pulmonary and pleural neoplasms were studied immunohistochemically with the monoclonal antibody HYB-612 which detects the multidrug resistance (MDR)-related P-glycoprotein (gp180). A tumor was considered positive for the expression of the MDR phenotype, even if a single rare positive cell was detected. Using this criterion, all of the various histologic subtypes were found to express MDR to varying degrees. The frequency of expression of this phenotype was found to be notably higher in non-small-cell carcinomas than in small-cell carcinomas. These findings are consistent with the known clinical responses of these neoplasms. The detection of gp180 in untreated lung neoplasms may be predictive of the responsiveness of neoplasms to chemotherapeutic agents. In addition, its presence or absence might be useful in determining the appropriate treatment protocol for given patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Immunohistochemical analysis of pulmonary and pleural neoplasms using a monoclonal antibody (47D10) which reacts with nonspecific cross-reacting antigen.

A series of 251 human pulmonary carcinomas were analyzed immunohistochemically for the antigens recognized by a new monoclonal antibody (MAb) 47D10. These antigens are part of a complex family of substances similar to, yet distinct from carcinoembryonic antigen (CEA), and are termed 'nonspecific cross-reacting antigens' (NCAs). The NCA epitope recognized by the MAb 47D10 is expressed on the cell surface and has previously been shown to be distinct from epitopes detected by several anti-CEA MAbs, as well as by MAbs 19-9 and Du-PAN-2. The NCA epitope recognized by MAb 47D10 is well preserved in formalin-fixed and paraffin-embedded tissues. Using immunohistochemistry, this epitope has been shown to have a limited biodistribution in normal tissues, and to be expressed by adenocarcinomas arising in the pancreas, colon, breast, ovary, prostate and lung. The frequency and pattern of NCA expression in human pulmonary neoplasms was found to correlate with the known distribution of CEA: and was often present in the non-small-cell carcinomas. In addition, the expression of CEA relative to NCA was evaluated in a select group of non-small-cell carcinoma cases using several anti-CEA MAbs, to directly compare the expression of CEA to NCA. In general, the NCA reaction pattern is more intense and expressed on more cells within the tumors than that of CEA expression.

Antibodies, Monoclonal↗
PubMed1989

Purification of supercoiled plasmids from crude cell lysates using high performance anion exchange chromatography.

High performance liquid chromatography is of increasing importance in the purification of nucleic acids. Recently, a new anion exchange column called Gen-Pak FAX has been introduced for this purpose. Previously, it has been used in the purification of restriction fragments and oligonucleotides. In this paper we present the use of the Gen-Pak FAX column for the purification of plasmids from crude E. coli lysates. The different conformational forms of the plasmid can be well separated and collected with high recoveries of both mass and activity. Up to 50 micrograms of supercoiled plasmid can be purified in a single 30 min run with up to 98% purity.

Biotechnology↗
PubMed1989

Characterization of the translocation between chromosomes X and 18 in human synovial sarcomas.

Recent studies have identified a specific chromosomal translocation, t(X;18)(p11.2;q11.2), in a high proportion of human synovial sarcomas. As a first step towards characterizing the X;18 translocation we have established a synovial sarcoma cell line. Fusion of this cell line to mouse RAG cells gave rise to somatic cell hybrids that contain the derivative (X) marker chromosome in the absence of other genetic material from chromosomes 18 and X. Southern analysis of DNA from these somatic cell hybrids demonstrated that the human X chromosome markers DXS94, DXS14, DXZ1 and DXS62 were retained. In contrast DXS7, GAPDP1, ARAF1, DXS146 were not consistently present in the hybrids indicating that these markers were on the region of the X chromosome replaced by part of the long arm of chromosome 18 during the generation of the X;18 translocation. The predicted position of the translocation relative to X chromosome markers is DXS7-DXS146-X; 18-DXS14-DXZ1-DXS94.

Chromosome Banding↗
PubMed1988

Activated Ki-ras genes in bladder epithelial cell lines transformed by treatment of primary mouse bladder explant cultures with 7,12-dimethylbenz[a]anthracene.

DNA from five lines of transformed bladder epithelial cells derived from cultures of primary cells that had been treated with 7,12-dimethylbenz[a]anthracene (DMBA) can transform NIH 3T3 mouse fibroblasts in DNA transfection experiments. Southern analysis of DNA from NIH 3T3 primary and secondary transformants established that four of the DMBA-transformed cell lines contained activated cellular Ki-ras, while the remaining cell line contained a transforming gene that is unrelated to Ki-ras, N-ras, and Ha-ras. The point mutations responsible for Ki-ras activation were detected using oligonucleotide probes following selective amplification of Ki-ras specific sequences using the polymerase chain reaction. The results showed that activation of Ki-ras invariably involved a GC----AT transition mutation of the first position of codon 12. Surprisingly, a Ki-ras gene that was activated by a GC----AT transition mutation at the same position was also detected in a single transformed bladder urothelial cell line derived from control cultures of mouse bladder cells. Together, our results indicate that Ki-ras activation in the DMBA-transformed bladder cell lines may not be a direct consequence of interaction of activated DMBA metabolites with the Ki-ras gene.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Preoperative combined modality therapy for stage III M0 non-small cell lung carcinoma.

More than 1/3 of all non-small cell lung carcinoma (NSCLC) patients present with locally advanced non-metastatic disease. Despite radiation therapy and surgery the survival of these patients remains poor. In an effort to improve upon these results 33 clinical Stage III M0 patients from April 1985 through September 1986 were entered into a Phase II study at Rush-Presbyterian-St. Luke's Medical Center. Treatment included 5-FU by continuous infusion, VP-16, cisplatin and concurrent split course radiation therapy followed by surgical resection when possible. The overall clinical response rate is 74%. Fifty-seven percent of the preoperative group of patients went to surgery with a 100% resectability rate. These patients had a 50% pathologic complete response with no tumor found in the resected specimen. All surgical margins were free of disease and there were no operative deaths. This concurrent combined modality therapy is feasible with the major toxicities being leukopenia, nausea, and vomiting. With an overall median follow-up of 15 months, 36% of the patients remain alive. Overall local control is 71%. Actuarial observed 2 yr. survival is 33% and the median survival is 15 months. Histologic complete response appears to be an early indicator of the efficacy of this treatment regime. With 83% of the resected pathologic complete responders alive without evidence of disease, this preoperative combined modality therapy offers an appealing approach.

Adenocarcinoma↗
PubMed1988

Phase II trial of therapy with etoposide, 5-fluorouracil by continuous infusion, cisplatin, and simultaneous split-course radiation in stage III non-small cell bronchogenic carcinoma.

Survival of patients who have clinical stage IIIM0 non-small cell bronchogenic carcinoma remains relatively short despite treatment with either surgery or radiation. Results from a phase II study of simultaneous continuous infusion of 5-fluorouracil, cisplatin, and split-course radiation with or without surgery indicate that median survival duration in patients treated with this combined modality approach may be better than the median survival for patients treated with radiation alone. Etoposide has been added to this regimen, and 32 stage IIIM0 non-small cell lung cancer patients have been treated with the 3-drug regimen resulting in a 73% clinical partial remission rate. No residual tumor was found in 6 of 12 patients who had pulmonary resection after 4 courses of chemotherapy and radiation. The sites of failure in 8 patients with recurrent disease are as follows: local only, 3; distant only, 4; and local and distant, 1. The major toxicities have been leukopenia, nausea, and vomiting. The median leukocyte nadir was 2,400/mm3. A leukocyte count less than 1,000/mm3 was observed in 2 patients (7%), 1 of whom died of progressive pneumonia. All patients experienced nausea, vomiting, and anorexia. Severe esophagitis, dermatitis, and pneumonitis were not observed. Survival analysis has not been done because median follow-up time (326 days) is relatively short.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Induction of thymomas by N-methyl-N-nitrosourea in AKR mice: interaction between the chemical carcinogen and endogenous murine leukaemia viruses.

AKR mice develop thymomas spontaneously when greater than 6 months old but when young AKR mice are treated with N-methyl-N-nitrosourea (MNU) they develop thymomas at 3-6 months of age. In this study the potential role of oncogene activation in the development of both the spontaneous and MNU-induced thymomas in AKR mice has been examined by DNA transfection into NIH3T3 mouse fibroblasts and by Southern analysis of tumour DNA. The results show that a high proportion of MNU-induced thymomas contain activated cellular rasK while no activated cellular ras genes were detected in spontaneous thymomas. Southern analysis of tumour DNA revealed that 2/30 spontaneous tumours and 2/52 MNU-induced tumours contained alterations in the c-myc gene while 5/29 spontaneous tumours and 6/56 MNU-induced tumours contained alterations in the Pim-1 gene. A more detailed analysis of the Pim-1 gene demonstrated that the alterations observed in most MNU-induced and spontaneous tumours resulted from proviral integration at the 3' end of this gene. Our analyses also demonstrated that the majority of MNU-induced tumours, including those containing rearrangements in the Pim-1 gene, lacked the somatically acquired recombinant MCF proviruses that are present in most spontaneous AKR lymphomas. These results provide evidence that the mechanisms of development of MNU-induced and spontaneous tumours in AKR mice are distinct and the development of thymomas that contain proviral integrations at the Pim-1 locus in the MNU-treated AKR mice involve cooperation between the chemical carcinogen and endogenous murine leukaemia viruses.

Animals↗
PubMed1987

Significance of membrane thickness in the sonographic evaluation of twin gestations.

A retrospective study of 55 twin pregnancies was performed to determine the role of sonography in distinguishing between dichorionic and monochorionic diamniotic gestations solely by evaluating the thickness of the membrane between the fetuses. The presence of a thick dividing membrane indicated a dichorionic diamniotic gestation in 38 (90%) of 42 cases in which it was identified. Inability to identify a membrane between dichorionic diamniotic twins occurred most commonly during the third trimester. A thin membrane indicated monochorionic diamniotic twinning and was seen in three (25%) of 12 cases. Membrane thickness was indeterminate in one case. Therefore, on the basis of the thickness of the dividing membrane imaged by sonography, dichorionic diamniotic gestations can be distinguished from monochorionic diamniotic gestations. Inability to show a separating membrane by sonography, however, can occur with any form of twin gestation, particularly in the third trimester. Membrane thickness should be used in conjunction with other sonographic criteria to predict the amnionicity and chorionicity of twin gestations.

Extraembryonic Membranes↗
PubMed1986

Phase II trial of etoposide, cisplatin, continuous infusion 5-fluorouracil, and simultaneous split-course radiation therapy in stage III non-small-cell bronchogenic carcinoma.

Survival in patients with locally advanced, non-small-cell lung cancer (NSCLC) is relatively short, despite treatment with surgery or radiation. A phase II study of simultaneous continuous infusion 5-fluorouracil and split-course radiation with or without surgery has shown possible improvement in median survival compared with that observed in trials of radiation alone. Past success with etoposide plus cisplatin in NSCLC has led to the addition of etoposide to the 5-fluorouracil plus cisplatin plus radiation combination. Twenty-four stage III NSCLC patients were treated with this three-drug regimen, and a 74% clinical partial remission rate was observed. Thoracotomy was done in eight of these patients; subsequent histologic examination of the resected specimen revealed no residual tumor in four patients (50%) and only microscopic foci of tumor in two patients (25%). Major toxicities were leukopenia, nausea, and vomiting. Median leukocyte nadir was 2,900/mm3. A leukocyte count less than 1,000/mm3 was observed in two of 24 patients (8%), one of whom expired from progressive pneumonia. All patients experienced nausea and vomiting, which were classified as moderate in three patients (12%) and severe in four (16%). Moderate to severe esophagitis, dermatitis, and pneumonitis were not observed. Median progression-free interval and median survival were not reached after a median follow-up of 163 days.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Estradiol is responsible for reduced renal prostaglandin dehydrogenase activity in female rats.

The contribution of sex steroids to sex-related differences in renal prostaglandin dehydrogenase activity and urinary prostaglandin excretion was examined in 7-8-week-old male and female rats subjected to sham-operation or gonadectomy at 3 weeks of age. Rats were injected subcutaneously twice over a 6-day interval with vehicle (peanut oil, 0.5 mg/kg) or with depot forms of testosterone (10 mg/kg), estradiol (0.1 mg/kg), progesterone (5 mg/kg), or with estradiol and progesterone combined (0.1 and 5 mg/kg). After the second injection, 24-h urine samples were collected for prostaglandin measurement by radioimmunoassay; the rats were killed, and renal and pulmonary prostaglandin dehydrogenase activities were determined by radiochemical assay. Renal prostaglandin dehydrogenase activity was 10-times higher in intact male rats than in intact females. Gonadectomy increased renal prostaglandin dehydrogenase activity 4-fold in females, but had no effect in males; estradiol, alone or combined with progesterone, markedly suppressed renal prostaglandin dehydrogenase activity in both sexes, while testosterone or progesterone alone had no effect. Pulmonary prostaglandin dehydrogenase did not differ between the sexes and was unaffected by gonadectomy or sex-steroid treatment. Intact female sham-operated rats excreted 70-100% more prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha in urine than did males; gonadectomy abolished the difference in urinary prostaglandin E2 excretion. Estradiol decreased urinary prostaglandin E2 in females but not in males; treatment with other sex steroids did not alter urinary prostaglandin excretion.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Community-acquired bacteremic urosepsis in the elderly patients: a prospective study of 34 consecutive episodes.

A prospective study was done on the clinical, laboratory, radiological, immunological and therapeutic features of acute, symptomatic, bacteremic urosepsis in 34 consecutive, elderly patients who required hospitalization. Urinary tract infection was identified as the most common cause of gram-negative bacteremia in elderly patients admitted to a community hospital. Appropriate antibiotic therapy and a lack of serious associated medical illnesses contributed to the high survival rate. Bacteremia and shock occurring in the wake of pyelonephritis develop more commonly in elderly than in young women. In the elderly patient with bacteremia and pyelonephritis radiographic evaluation invariably demonstrates obstruction to urine flow, calculous disease or abscess. Guidelines are provided for the therapy of acute, symptomatic bacteremic urosepsis.

Aged↗