AZT trial in Thailand.
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Antiviral Agents↗
Biomedical subjects
T Brennan
Publications and source records attributed to T Brennan.
An automated multiplex oligonucleotide synthesizer: development of high-throughput, low-cost DNA synthesis.
An automated oligonucleotide synthesizer has been developed that can simultaneously and rapidly synthesize up to 96 different oligonucleotides in a 96-well microtiter format using phosphoramidite synthesis chemistry. A modified 96-well plate is positioned under reagent valve banks, and appropriate reagents are delivered into individual wells containing the growing oligonucleotide chain, which is bound to a solid support. Each well has a filter bottom that enables the removal of spent reagents while retaining the solid support matrix. A seal design is employed to control synthesis environment and the entire instrument is automated via computer control. Synthesis cycle times for 96 couplings are < 11 min, allowing a plate of 96 20-mers to be synthesized in < 5 hr. Oligonucleotide synthesis quality is comparable to commercial machines, with average coupling efficiencies routinely > 98% across the entire 96-well plate. No significant well-to-well variations in synthesis quality have been observed in > 6000 oligonucleotides synthesized to date. The reduced reagent usage and increased capacity allow the overall synthesis cost to drop by at least a factor of 10. With the development of this instrument, it is now practical and cost-effective to synthesize thousands to tens of thousands of oligonucleotides.
Amides↗
Self-care strategies used for acute attack of interstitial cystitis.
OBJECTIVE: To determine the kinds of self-care used by women with interstitial cystitis and to find effective ways to manage symptoms of acute attack. STUDY DESIGN: One hundred thirty-eight women with interstitial cystitis completed a survey indicating how often they used and how effective they found strategies in four physical self-care subdomains (medication, treatment, diet, and body comfort) and three psychologic self-care subdomains (cognitive/stress reduction, distraction, and help-seeking). RESULTS: Descriptions of symptoms during an "acute attack" are more consistent with symptoms described "at onset" than symptoms experienced "currently." Physical strategies most used for acute attack included use of narcotics, antidepressants, and bladder analgesics, in addition to limiting the diet to bland or starchy foods, wearing loose clothing, taking hot baths, and using a heating pad over the pubis. Psychologic strategies most used included watching television, prayer, and seeking support from a significant other, family members, friends, and other patients with interstitial cystitis. CONCLUSIONS: Some psychologic and physical strategies found to be effective for other chronic pain conditions, such as biofeedback, alternating use of heat/cold, self-hypnosis, and redefining pain sensations were seldom used. Other nonmedical interventions such as massage and imagery, when used, were found to be more moderately to highly effective. Information about self-care and access to support groups may increase exposure to multiple ways of handling acute attacks.
Acute Disease↗
Use and effectiveness of sexual self-care strategies for interstitial cystitis.
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Adult↗
Use and effectiveness of physical self-care strategies for interstitial cystitis.
Interstitial cystitis is a painful disease that primarily affects women. It involves a chronic bladder inflammation of unknown etiology and unpredictable course. There is no consensus about treatment. Women with interstitial cystitis report using multiple strategies and interventions to prevent and manage urinary urgency, frequency, and suprapubic pain. A survey questionnaire on self-care strategies was completed by 138 members of the Interstitial Cystitis Association. Subjects indicated how often they used more than 300 self-care strategies and the effectiveness of these strategies. This article reports findings from five physical subdomains (medications, treatments, hygiene, diet, and body comfort). Among those who report actually using the methods the effectiveness ratings for many body comfort strategies are comparable to the reported effectiveness of medications (including narcotics) for managing mild to moderate symptoms.
Chronic Disease↗
Overview of legal issues.
Evidence suggests that compliance with guidelines will affect malpractice litigation. One point often overlooked is that guidelines can provide both exculpatory and inculpatory evidence.
Cost Control↗
Differential trans-activation of a muscle-specific enhancer by myogenic helix-loop-helix proteins is separable from DNA binding.
The muscle creatine kinase (MCK) enhancer was used as a target to study the specificity of DNA binding and trans-activation by members of the helix-loop-helix (HLH) family of myogenic regulatory factors, MyoD1, myogenin, myf-5, and MRF4. Whereas all four myogenic factors bound with similar affinities to the MCK enhancer in the presence of the widely expressed HLH protein E12, only MyoD1, myogenin, and myf-5 efficiently trans-activated the enhancer in transiently transfected 10T1/2 and 3T3 cells. That MRF4 binds the MCK enhancer without activating transcription suggests that domains in addition to those required for DNA binding are important for transcriptional activation and supports the notion that the different members of the HLH family of myogenic regulatory factors may selectively regulate unique sets of muscle-specific genes.
Cells, Cultured↗
Evaluation of a commercial measles virus immunoglobulin M enzyme immunoassay.
Paired serum samples from 93 patients suspected of having measles were assayed for measles virus-specific immunoglobulin M (IgM) antibodies by an enzyme immunoassay (EIA), and the results were compared with results from a complement fixation assay and an EIA for measles virus IgG. By using significant serologic rises as the standard for comparison, the IgM EIA assay had a sensitivity of 85.7%, a specificity of 81.3%, a positive predictive value of 95.7%, and a negative predictive value of 54.2%. This assay can be expected to perform well in outbreak situations.
Complement Fixation Tests↗
Cytomegalovirus antibody in the elderly.
Presence of cytomegalovirus (CMV) specific immunoglobulin M (IgM) is generally considered strong evidence of current or recent CMV infection. Sera from 110 elderly individuals (age range 61-100 years) were compared with sera from 87 younger individuals (age range 16-47 years). Prevalence of CMV IgM was found to be 30% in the older group (mean age 83 years) and only 6% in the younger group (mean age 29 years). In spite of increased CMV antibody levels, none of the elderly individuals were symptomatic. Viral cultures of urine from 72 elderly individuals were negative for CMV. These results suggest that the presence of CMV-specific IgM must be interpreted with caution in an elderly population.
Adolescent↗
Medical ethics and medical injuries: taking our duties seriously.
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Colonic Diseases↗
Sensitivities of NIH/3T3-derived clonal cell lines to ionizing radiation: significance for gene transfer studies.
Rodent cells are frequently used as recipients in experiments involving gene transfer, isolation, and characterization. The present studies were designed to investigate the clonal responses to ionizing radiation of NIH/3T3 cells subjected to DNA-mediated gene transfer. Radiation sensitivity (D0) values were determined for the parental NIH/3T3 cell strain, six clonal cell lines transfected with DNA from radiation-resistant human tumor cells, and six nontransfected clonal cell lines. The radiation sensitivities of four transfected and two nontransfected clonal cell lines differed significantly from parental NIH/3T3 cells (P less than 0.05). Detailed karyotype analysis of two nontransfected clonal cell lines with differing radiation sensitivities showed variation in chromosomal composition. Specifically, a minute chromosome was observed to segregate consistently (in 49 of 50 metaphases) with the genome of one NIH/3T3 clone (D0 2.07 Gy) and was completely absent (from 50 metaphases) in another NIH/3T3 clone (D0 1.06 Gy). In the parental NIH/3T3 strain (D0 2.02 Gy) 10% of cells (3 of 30 metaphases) had such minute chromosomes. These findings demonstrate that the clonal cellular heterogeneity of NIH/3T3 cells is characterized by genotypic and phenotypic variations which must be considered in the experimental design involving gene transfer and expression.
Animals↗
Effect of antisense c-raf-1 on tumorigenicity and radiation sensitivity of a human squamous carcinoma.
Antisense RNA-mediated inhibition of gene expression was used to investigate the biological function of the c-raf-1 gene in a radiation-resistant human squamous carcinoma cell line, SQ-20B. S1 nuclease protection assays revealed that transfection of full-length raf complementary DNA in the antisense orientation (AS) leads to a specific reduction (greater than tenfold) of steady-state levels of the endogenous c-raf-1 sense (S) transcript in SQ-20B cells. In nude mice, the malignant potential of SQ-20B cells transfected with raf (S) was significantly increased relative to that of SQ-20B cells transfected with raf (AS). SQ-20B cells containing transfected raf (S) maintained a radiation-resistant phenotype as compared to those cells harboring the AS version, which appeared to have enhanced radiation sensitivity. These data indicate that the reduced expression of endogenous c-raf-1 is sufficient to modulate the tumorigenicity and the radiation-resistant phenotype of SQ-20B cells, thus implicating c-raf-1 in a pathway important to the genesis of this type of cancer.
Animals↗
Comparative studies of three serologic methods for the measurement of Mycoplasma pneumoniae antibodies.
Antibodies against Mycoplasma pneumoniae in the sera of patients and normal adult controls were measured by a standard complement fixation (CF) test, a commercial immunofluorescence (IF) test (CROWNTITRE), and a commercial enzyme-linked immunosorbent assay (ELISA) (MYCOPLASMELISA). The findings showed that, in the control sera, 269 of 277 (97%) had negative results for CF antibodies. Of the 320 controls tested by the IF assay, all (100%) had negative results for IgM antibodies and 314 (98%) had negative results for IgG antibodies. Only 6 of the 201 (3%) controls by the ELISA were classified as negative/equivocal. Among the 450 patient sera, 105 (23%) had positive results for CF antibodies, and 158 (35%) had positive results for IgG and/or IgM membrane antibodies by the IF test; 424 of these patients' sera were also tested by the ELISA, and 397 (94%) of them were found to have positive results for anti-M. pneumoniae IgG antibodies. If the CF test were chosen as the standard for comparison, the IF test would have a sensitivity of 87% and a specificity of 81% and the ELISA would have a sensitivity of 71% and a specificity of 80%, provided an adjustment in the threshold ELISA-positive value was made. A single positive M. pneumoniae membrane IgM antibody titer appeared to be valuable for a presumptive diagnosis of an ongoing infection; 41 of 47 (87%) of the IgM-positive results in the paired sera were supported by a fourfold increase or a stable high level of CF antibody titer.
Antibodies, Bacterial↗
Comment on the significance of positive carcinogenicity studies using gavage as the route of exposure.
There is continuing controversy, extending into regulatory matters, over the significance to human health of positive results in carcinogenicity studies in animals using the gavage technique as the route of exposure. Our review of a nonrandom sample of 117 chemicals or chemical processes listed as known or reasonably anticipated to be carcinogenic in the National Toxicology Program's Third Annual Report on Carcinogens provides support for the validity of the gavage route in such studies. Twenty-three chemicals among the 117 substances and processes listed were positive by gavage. Twenty of these 23 chemicals were also appropriately studied by at least one other route of exposure. Thus, we were able to evaluate the extent to which positive gavage results were confirmed by another route of exposure in this sample. Nineteen (or 95%) of the twenty chemicals were positive for carcinogenicity by at least one other nongavage route in carcinogenicity bioassays. Moreover, in each of these 19 cases, positive carcinogenesis results were obtained by a nongavage route in the same species of animal where gavage administration led to the induction of cancer. All of the 23 gavage-positive chemicals induced tumors distal to the site of administration in at least one study, as did all 15 chemicals which were also positive by subcutaneous injection. We emphasize, however, the limited scope of our survey. We have not evaluated all chemicals that have tested positive by gavage and by at least one alternative route, nor have we assessed those chemicals found to be negative by the gavage route.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Differential radiosensitization of human tumour cells by 3-aminobenzamide and benzamide: inhibitors of poly(ADP-ribosylation).
The effect of 3-aminobenzamide (3AB) and benzamide (BZ) (inhibitors of poly(ADP-ribose) synthetase) on radiosensitivity was investigated in normal human fibroblasts and three human cell lines established from tumours with varying degrees of clinical radiocurability. The human tumour cell lines selected were: Ewing's sarcoma, a bone tumour usually considered radiocurable with moderate radiation doses; lung adenocarcinoma, a tumour considered radiocurable with high doses of radiotherapy; and osteosarcoma, a very resistant tumour which is rarely controlled by standard doses of radiotherapy. Poly(ADP-ribose) synthetase inhibitors were added to cultures 2 h prior to irradiation and removed 24 h after. Inhibitors were used at doses producing little or no toxicity in cells. In the presence of these inhibitors, a differential radiosensitization was observed. Ewing's sarcoma cells and normal human fibroblasts were sensitized to an equal extent by either 8 mM 3AB or 4 mM BZ. However, no sensitization was observed at these concentrations in the lung adenocarcinoma cells or osteosarcoma cells. The degree of radiosensitization in vitro by 3AB and BZ correlates well with the clinical radiocurability of these tumours in vivo.
Benzamides↗
Cytomegalovirus antibody detection by three commercially available assays and complement fixation.
Four methods (complement fixation, latex agglutination, qualitative EIA, and quantitative EIA) for detecting antibody to cytomegalovirus (CMV) were compared by testing 103 sera. When ranked according to accuracy, sensitivity, and specificity, the complement fixation test was third, fourth, and first; the latex agglutination test was first, second, and third; the qualitative EIA was fourth, first, and fourth, whereas the quantitative EIA was second, third, and first, respectively. In addition, the complement fixation, latex agglutination, and quantitative EIA systems each satisfactorily detected significant antibody rises in paired sera.
Antibodies, Viral↗
Determination of infection and immunity to varicella-zoster virus with an enzyme-linked immunosorbent assay.
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Adult↗
Rapid herpes simplex virus detection in clinical samples submitted to a state virology laboratory.
Of 16,779 specimens received for herpes simplex virus (HSV) isolation since 1982, 4,465 (26.6%) were positive for HSV by either standard tissue culture or an antigen detection system (peroxidase-antiperoxidase; PAP). The overall isolation rate for genital vesicle specimens was lower (26.1%) than that for nongenital specimens (29.3%). Monthly isolation rates ranged from 19 to 32% for genital specimens and from 20 to 44% for nongenital specimens. Increasing demands for HSV isolation led to comparison of tissue culture with PAP. In the first comparison, HSV was isolated in single human fibroblast cell cultures from 1,019 of 4,261 specimens (23.9%), whereas single human fibroblast wells stained at 24 and 72 h postinoculation were PAP positive for 1,007 of 4,261 specimens (23.6%). In the second comparison, HSV was isolated from 225 of 1,026 (21.9%) specimens and duplicate human foreskin fibroblast cell wells stained at 24 and 72 h were PAP positive in 241 of 1,026 (23.5%). With the dual-well PAP system, all results were reported within 72 h, approximately 70% of positives were reported within 24 h, and considerable savings in time and materials resulted.
Antigens, Viral↗