Search PubMed⌕ Search

Biomedical subjects

B A Neilan

Publications and source records attributed to B A Neilan.

At least 55 records · Page 3Linked to original sources
PubMed1995

Genetic diversity and phylogeny of toxic cyanobacteria determined by DNA polymorphisms within the phycocyanin locus.

Cyanobacteria are a highly diverse group in relation to form, function, and habitat. Current cyanobacterial systematics relies on the observation of minor and plastic morphological characters. Accurate and reliable delineation of toxic and bloom-forming strains of cyanobacteria has not been possible by traditional methods. We have designed general primers to the phycocyanin operon (cpc gene) and developed a PCR which allows the amplification of a region of this gene, including a variable intergenic spacer sequence. Because of the specificity of this PCR for cyanobacterial isolates, the assay is appropriate for the rapid and reliable identification of strains in freshwater samples. Successive restriction endonuclease digestion of this amplification product, with a total of nine enzymes, yielded many identifying DNA profiles specific to the various taxonomic levels of cyanobacteria. The restriction enzyme profiles for MspI, RsaI, and TaqI were conserved for strains within each of the eight genera (40 strains) studied and clearly discriminated among these genera. Intrageneric delineation of strains was revealed by the enzymes AluI, CfoI, and HaeIII for members of the genus Microcystis, while strains of genus Anabaena were differentiated by the digestion patterns provided by AluI, CfoI, and ScrFI. Phenetic and cladistic analyses of the data were used to infer the genetic relatedness and evolution of toxic and bloom-forming cyanobacteria.

Base Sequence↗
PubMed1995

Identification and phylogenetic analysis of toxigenic cyanobacteria by multiplex randomly amplified polymorphic DNA PCR.

Randomly amplified polymorphic DNA PCR was used to generate unique and identifying DNA profiles for members of the cyanobacterial genera Anabaena and Microcystis, which are responsible for much of the production of nuisance blooms in various freshwater systems, including recreational and drinking water supplies. A method based on the combination of two 10-mer oligonucleotides in a single PCR was developed to provide specific and repeatable DNA fingerprints for cyanobacterial isolates. The strain-specific randomly amplified polymorphic DNA profiles made it possible to discriminate among all toxigenic cyanobacteria studied to the three taxonomic levels of genus, species, and strain. Analysis of DNA typing results obtained by the described method clearly distinguishes between the genera Anabaena and Microcystis. The markers produced for each strain were also applied to a phylogenetic analysis to infer genetic relatedness in this group of prokaryotes.

Journal Article↗
PubMed1994

16S ribosomal RNA gene sequence and phylogeny of toxic Microcystis sp. (cyanobacteria).

The toxigenic and bloom-forming cyanobacterial genus Microcystis contains several ill-defined species. The 16S rDNA for two strains of toxic M. aeruginosa were sequenced and compared to available cyanobacterial, bacterial, and chloroplast 16S rRNA gene information. Phylogeny and the validity of a molecular taxonomy for the genus Microcystis is presented.

Base Sequence↗
PubMed1994

Microsatellite genome screening: rapid non-denaturing, non-isotopic dinucleotide repeat analysis.

The study of reverse genetics has made it possible for scientists to isolate and identify the genes responsible for such human diseases as cystic fibrosis and Duchenne- and Becker-type muscular dystrophy. The expensive and time-consuming process of detecting restriction fragment length polymorphisms by Southern blotting was the only method available to localize these genes. With the discovery of polymorphic microsatellite sequences in the human genome, the speed and ease of which a genome screening can be performed has increased dramatically. This paper reports on advanced methods for detection of microsatellite-repeated sequences making the task of mapping human genes simpler, safer and more economical.

DNA, Satellite↗
PubMed1994

Oncologic emergencies. Treating acute problems resulting from cancer and chemotherapy.

Oncologic emergencies can occur in cancer patients who have a good prognosis. In all of them, the challenge to the clinician is to diagnose and treat before irreversible complications occur. In febrile patients with neutropenia, cultures of body fluids should be obtained and therapy should be started immediately with broad-spectrum antibiotics. If spinal cord compression is suspected, either magnetic resonance spectroscopy or complete myelography can be done to confirm the diagnosis. Prompt workup in cancer patients with headaches or seizures may avoid neurologic consequences. For brain metastases, immediate treatment with dexamethasone (Decadron, Dexone, Hexadrol) is indicated. For hypercalcemia, a number of drugs that inhibit bone resorption, resulting in lower serum calcium levels, are now available. Malignant cardiac tamponade is relatively rare but potentially lethal; emergency pericardiocentesis often results in marked improvement.

Antineoplastic Agents↗
PubMed1993

The rapid analysis of dystrophin gene deletions shows variable electrophoretic mobility.

The introduction of PCR technology to the molecular diagnosis of genetic diseases has increased the speed and range of DNA tests available. Previous analyses of dystrophin gene mutations were time consuming, taking weeks to complete, and used radioisotopic methods. Further developments in DNA amplification and post-amplification techniques have made conventional tube PCR redundant. The rapid methodologies described enable the efficient screening of large populations for genetic disorders, although precautions must be taken when analysing the PCR products.

Cross-Linking Reagents↗
PubMed1992

Direct PCR sequencing of dystrophin polymorphic CACA alleles after purification to remove shadow bands.

A method is described that allows the sequencing of polymerase chain reaction (PCR) products containing CACA repeats. The method was tested using a DNA polymorphism that exists at the 3' end of the dystrophin gene. This polymorphism consists of a variation in the length of a CACA dinucleotide repeat. Four alleles from a total of 16 individuals were sequenced at this locus after the DNA sequence had been amplified by the PCR. Five examples of each of the common alleles were sequenced. For each allele all five sequences were the same. The only example of a rare allele was also sequenced. The PCR products of DNA sequences containing dinucleotide repeats consist of a number of bands differing by 2 bp below the most intense main band. Previously, direct sequencing of the PCR products lead to ambiguities and smearing at and above the CACA repeat. In this paper, the main PCR band was cut out of a sequencing gel and directly sequenced to give a clear DNA sequence. Our results indicate that for a particular allele, all individuals had exactly the same DNA sequence. This implies that with the appropriate choice of oligonucleotide primers, polymorphisms could be detected without electrophoresis.

Alleles↗
PubMed1989

Phase II evaluation of bisantrene in acute leukemia. A Southwest Oncology Group Study.

Twenty-nine patients with heavily pretreated acute leukemia in relapse were treated with bisantrene (maximum dose 120 mg/m2/day x 5) in a phase II study. Twenty-seven of the 29 patients were evaluable for response, receiving a total of 53 courses of treatment. There were three complete remissions (11%) lasting 27, 107, and 115 days. One brief partial remission of 43 days was also seen for a total response rate of 15%. Toxicity was mainly limited to the expected myelotoxicity with minimal nonhematologic toxicity seen. Although the complete remission rate is low, an antileukemic effect was seen in the majority of the patients treated. Sixty-one percent of the patients had at least a 50% decrease in the circulating blast count and 32% had at least a 50% decrease in the number of bone marrow blasts. We conclude that bisantrene does have an antileukemic effect, but that the optimal starting dose is not yet established.

Acute Disease↗
PubMed1989

In vivo response of murine RIF tumors to thermochemotherapy.

The in vivo effects of hyperthermia combined with bleomycin, cis-platinum, or BCNU were studied. C3H mice with RIF tumors implanted on the dorsal aspect of their feet were used in these experiments. Heat alone (45 degrees C, 30 min) had a minimal effect on mean tumor growth delay (TGD), the time required for the tumor to reach twice the original tumor volume. The maximum tolerated dose (MTD), approximately equivalent to an LD10, of BCNU (50 mg/kg) gave a mean TGD of 24 days, while 40 mg/kg of BCNU (MTD for BCNU with heat) alone resulted in a mean TGD of only 5.5 days. No tumors were cured when treated with heat or chemotherapy alone. However, BCNU (40 mg/kg) given with concomitant heat (45 degrees C, 30 min) resulted in 9/12 cures (tumor control to 120 days). In the three remaining mice, there was one tumor growth, one foot amputation response and one death. The combinations of bleomycin-heat and cis-platinum-heat were inferior to BCNU-heat. Even the combination of bleomycin and cis-platinum with heat resulted in only 4/18 cures, with 5 tumor regrowths, 4 foot amputations, and 5 deaths. Thus, the combination of BCNU-heat gave the best in vivo response rate (75% cure) with acceptable toxicity.

Animals↗
PubMed1988

Interactions of BCNU, low pH, glucose and hyperthermia in cultured RIF cells.

The interactions of BCNU (1,3-bis[2-chloroethyl]-1-nitrosourea) with low pH, glucose and hyperthermia were studied in cultured RIF tumor cells. The effect of a mild heat treatment of 43 degrees C, 1 h at pH 7.4 on cell killing [surviving fraction (S) = 0.27 +/- 0.05, standard error of the mean (S.E.)] was significantly enhanced by pH 6.5 (S = 0.11 +/- 0.02, S.E.) and 50 mM D-glucose (S = 0.14 +/- 0.01, S.E.). When heat (43 degrees C, 1 h) was added to BCNU, cytotoxicity was increased approximately 14-fold over BCNU alone. Moreover, pH 6.5 increased killing with BCNU and heat by an additional factor of 28. The presence of glucose at 37 degrees C at either pH 6.5 or 7.4 reduced BCNU toxicity in a dose dependent fashion. However, the presence of glucose did not reduce cell killing by BCNU at 43 degrees C. As a result BCNU cytotoxicity was enhanced by approximately 2 orders of magnitude when tumor cell acidification (glucose and low pH) was combined with BCNU and heat.

Carmustine↗
PubMed1987

Colorectal cancer.

Colorectal cancer is one of the leading causes of death in older men and women. Therefore, this age-related cancer is of particular importance to geriatricians. The high incidence of this cancer may be decreased by dietary modifications recommended by the American Cancer Society. Early cancer detection is important to improve survival. When colorectal cancer is detected in the asymptomatic patient, there is a high likelihood of cure. Therefore, screening individuals at high risk is a major goal. Because age is the leading risk factor for colorectal cancer, the American Cancer Society has developed guidelines for screening individuals over age 40 years. Treatment decisions are based on stage of disease. For localized disease, surgical resection is the primary therapy. In advanced disease, palliative treatment may include the use of surgery, radiotherapy, chemotherapy, or a combination of these modalities. Because there is no evidence of an age effect, principles of treatment should be applied similarly in geriatric and younger patients.

Aged↗
PubMed1986

A phase II study of bisantrene in malignant lymphomas. A Southwest Oncology Group Study.

Forty evaluable patients with malignant lymphoma (ML) were treated with bisantrene at a dose of 260 mg/m2 every 3 weeks (18 patients) or 208 mg/m2 every 3 weeks (22 patients). The initial dose rate was determined on the basis of expected myelosuppression. Patients were heavily pretreated and had advanced disease (92% had stage IV). The overall response rate was 10% and included 1 partial response (PR) in 17 patients with Hodgkin's disease (HD), 1 PR and 1 complete response (CR) in 5 patients with favorable histology in non-Hodgkin's lymphoma (NHL), and 1 PR in 18 patients with unfavorable histology in NHL. Neutropenia (WBC less than or equal to 3000 cells/microliter) was the most common toxicity, occurring in 50% of patients. Phlebitis was a common side effect in patients treated with bisantrene administered by way of peripheral veins. Bisantrene has limited activity in heavily pretreated patients with HD or unfavorable histology in NHL. The role of bisantrene for treatment of NHL with favorable histology or for treatment at an earlier point in the natural history of ML is unknown.

Anthracenes↗
PubMed1986

Cytotoxicity of hyperthermia combined with bleomycin or cis-platinum in cultured RIF cells: modification by thermotolerance and by polyhydroxy compounds.

The effect of thermotolerance and of polyhydroxy compounds on the cytotoxicity of bleomycin and cis-platinum was studied in cultured RIF tumor cells. Cell survival in response to drug-heat treatments was compared in cells not previously exposed to hyperthermia and in preheated cells that had developed thermotolerance. Since cellular accumulation of polyhydroxy compounds is a potential mechanistic basis of thermotolerance, we also compared cell survival of thermotolerant cells and chemically heat-protected cells. The cytotoxicity of bleomycin and cis-platinum in control cells treated with drug plus heat (43 degrees C, 1 h) was increased synergistically over the cytotoxicity of drug and heat alone. In thermotolerant cells, the synergistic interaction was largely reversed with the bleomycin-heat combination but retained with cis-platinum at 43 degrees C. In the absence of heat, bleomycin and cis-platinum showed similar cytotoxicity in control and thermotolerant cells. The addition of heat protectors (erythritol or galactose) modified the drug-heat cytotoxicity similar to thermotolerance. The synergistic interaction of bleomycin-43 degrees C, but not cis-platinum-43 degrees C, was reversed by the polyhydroxy compounds.

Bleomycin↗
PubMed1985

Phase II study of aziridinylbenzoquinone (AZQ) in patients with central nervous system malignancies: a Southwest Oncology Group Study.

AZQ, an alkylating agent with lipophilic characteristics allowing CNS penetration was studied in patients with primary CNS malignancies refractory to surgical and radiotherapeutic modalities. Responses were evaluated by three criteria: neurologic examination, performance status and CT scan of the brain. Improvement in all three parameters with stable or decreasing doses of decadron was required for a partial response. Thirty-six poor risk (prior chemotherapy) patients with Grades III and IV astrocytomas were treated with 30 mg/m2. Three patients had a partial response (14, 17, 60 weeks duration). Two patients had mixed responses (worsening of one disease parameter with improvement in another), four had stable disease and one patient had improvement in neurologic parameters with a stable CT scan. Twenty-six patients had increasing disease. Fifteen good risk patients (no prior chemotherapy) with recurrent grades III and IV astrocytomas were treated at a dose of 40 mg/m2 intravenously every three weeks. There were no objective responses in this group of patients. Three patients with nonastrocytomas were treated and no responses observed. The drug was well tolerated. Myelosuppression in the form of leukopenia and thrombocytopenia was the major toxicity. Myelosuppression required dose reductions in eight patients and discontinuation of therapy due to repeated treatment delays in two patients. AZQ at doses of 30 and 40 mg/m2 given on an intermittent bolus schedule is inactive in patients with Grades III and IV recurrent astrocytoma.

Adult↗
PubMed1985

Management of cancer in the elderly. Implications of the aging process.

Cancer is one of the most serious illnesses of the elderly. Screening programs focusing on its early detection in this age-group are needed to allow maximum opportunity for cure. Also important is convincing the older patients who smoke that stopping is still worthwhile. Compared with younger patients, the elderly have more intercurrent medical illnesses and are more likely to suffer from financial difficulties and loss of family support. These factors must be considered when managing these patients. Although age-imposed compromises in treatment are often made, available data suggest that a priori dose reduction of chemotherapy on the basis of age alone is not indicated in patients with solid tumors. Prospective clinical trials are needed to further address the issue of responsiveness to chemotherapy as a function of age. Such trials should include assessment of physiologic age and quality of life.

Aged↗