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Biomedical subjects

D A Johnston

Publications and source records attributed to D A Johnston.

At least 19 recordsLinked to original sources
PubMed1999

Image analysis of papillary thyroid carcinoma fine-needle aspirates: significant association between aneuploidy and death from disease.

BACKGROUND: Papillary thyroid carcinoma is the most common thyroid malignancy in the U.S. As many as half of patients with papillary carcinoma present with cervical lymph node metastases at the time of diagnosis. Metastatic disease involving cervical lymph node tissue has not historically been proven to correlate with a more aggressive course; however, distant metastases worsen prognosis. METHODS: Diagnostic fine-needle aspiration (FNA) smears from 26 primary and metastatic papillary carcinomas underwent Feulgen reaction and were studied by image analysis to determine DNA pattern, proliferation index, and the percentage of cells with DNA content >5C. The medical records of all the patients were reviewed for metastatic disease pattern and survival data. For metastatic pattern, two groups were defined: 1) confined to thyroid/local lymph node metastases/soft tissues of the neck involved by tumor, and 2) distant metastases. RESULTS: Among the 26 patients, 16 had "nonaggressive" DNA patterns described as diploid, abnormal diploid, or tetraploid, and 10 had "aggressive" DNA patterns described as aneuploid. Only 2 of the 16 patients in the "nonaggressive" DNA pattern group developed distant metastases, whereas 5 of the 10 patients in the aneuploid group developed distant metastatic disease. In addition, none of the 16 patients with "nonaggressive" DNA patterns died of disease, whereas 3 of the 10 individuals with DNA histograms interpreted as aneuploid did die of metastatic disease complications. CONCLUSIONS: Aneuploidy identified by image analysis of FNA of papillary thyroid carcinoma is significantly associated with death from papillary carcinoma (log rank test, P=0.027).

Adolescent↗
PubMed1999

Genomics and the biology of parasites.

Despite the advances of modern medicine, the threat of chronic illness, disfigurement, or death that can result from parasitic infection still affects the majority of the world population, retarding economic development. For most parasitic diseases, current therapeutics often leave much to be desired in terms of administration regime, toxicity, or effectiveness and potential vaccines are a long way from market. Our best prospects for identifying new targets for drug, vaccine, and diagnostics development and for dissecting the biological basis of drug resistance, antigenic diversity, infectivity and pathology lie in parasite genome analysis, and international mapping and gene discovery initiatives are under way for a variety of protozoan and helminth parasites. These are far from ideal experimental organisms, and the influence of biological and genomic characteristics on experimental approaches is discussed, progress is reviewed and future prospects are examined.

Animals↗
PubMed1999

MRI of primary lymphoma of bone: cortical disorder as a criterion for differential diagnosis.

To investigate the pattern and dimension of cortical bone abnormality on magnetic resonance imaging (MRI) as a feature to distinguish primary lymphoma of bone from osteosarcoma and Ewing sarcoma, 46 patients with primary malignant bone lesions with a soft tissue mass (16 osteosarcomas, 15 Ewing sarcomas, 15 lymphomas) were examined with MRI (T1-weighted pre-/postcontrast spin-echo sequences and T2-weighted spin-echo and fast spin-echo sequences; 1.5 T system). Qualitative image analysis revealed no differences for signal characteristics and enhancement. Lymphomas appeared significantly more often homogeneous (47%; Ewing sarcoma 20%; osteosarcoma 6%/o), and patients were significantly older (cutoff point 30 years). Lymphomas showed significantly less frequent cortical abnormality (60%; Ewing sarcoma 87%; osteosarcoma 100%), complete penetration (13%; Ewing sarcoma 67%; osteosarcoma 87%), focal destruction (13%; Ewing sarcoma 40%; osteosarcoma 81%), and complete destruction (0%; Ewing sarcoma 13%; osteosarcoma 19%). In conclusion, primary lymphoma of bone is characterized by minimal cortical changes despite an accompanying soft tissue mass in a patient over 30 years of age.

Adolescent↗
PubMed1999

Aneuploidy index in blood: a potential marker for early onset, androgen response, and metastasis in human prostate cancer.

OBJECTIVES: To investigate whether the frequency of chromosome abnormalities in peripheral blood lymphocytes defined as the aneuploidy index in blood (AnIB) can be used as a clinical marker of early age onset, androgen response, and metastasis in human prostate cancer. METHODS: Peripheral blood samples were collected from 80 patients with prostate cancer, and chromosome preparations were made from 72-hour cultures after mitotic block. The AnIB of 59 informative cases was compared with several parameters, including age at disease onset, Gleason grade of tumor, clinical stage of tumor, metastasis, and prostate-specific antigen (PSA) level. RESULTS: Patients with AnIB levels greater than 3 had a significantly higher incidence of metastasis (P = 0.022), androgen-independent disease (P = 0.002), and early age at disease onset (age at diagnosis less than 65 years) (P = 0.002) compared with the patients with lower AnIB (less than 3) levels. In addition, patients with AnIB levels greater than 5 had higher PSA levels (greater than 20 ng/mL) (P = 0.029) than patients with AnIB levels less than 5. CONCLUSIONS: Chromosome abnormalities can be detected in the peripheral lymphocytes of patients with prostate cancer, and AnIB can be used as an early diagnostic and predictive marker for prostate cancer metastasis and androgen-independent disease.

Age of Onset↗
PubMed1999

Helminth genome analysis: the current status of the filarial and schistosome genome projects. Filarial Genome Project. Schistosome Genome Project.

Genome projects for the parasitic helminths Brugia malayi (a representative filarial nematode) and Schistosoma were initiated in 1995 by the World Health Organization with the ultimate objectives of identifying new vaccine candidates and drug targets and of developing low resolution genome maps. Because no genetic maps are available, and very few genes have been characterized from either parasite group, the first goal of both Initiatives has been to catalogue new genes for future placement on chromosome and physical maps. These genes have been identified by the expressed sequence tag (EST) approach, utilising cDNA libraries constructed from diverse life cycle stages. To date, the Initiatives have deposited over 16,000 Brugia ESTs and nearly 8000 Schistosoma ESTs in Genbank's dbEST database, corresponding to 6000 and over 3600 genes respectively (33% of Brugia's estimated gene compliment, 18-24% of that of Schistosoma). Large fragment, genomic libraries have been constructed in BAC and YAC vectors for studies of genomic organization and for physical and chromosome mapping, and public, hypertext genomic databases have been established to facilitate data access. We present a summary of progress within the helminth genome initiatives and give several examples of important gene discoveries and future applications of these data.

Animals↗
PubMed1999

Prescription of acid-suppressing drugs in relation to endoscopic diagnosis: a record-linkage study.

BACKGROUND: Although widely used, few data are available on the appropriateness of prescribing of acid-suppressing drugs (ASDs), despite guidelines on the investigation and treatment of dyspeptic patients. METHODS: We created a database of 62 000 endoscopy examinations and record-linked these to a prescribing database. Endoscopic diagnoses were classified into peptic, nonpeptic and others. The H2-antagonists, omeprazole and misoprostol, were studied. RESULTS: 35 000 patients had one or more endoscopies during 1978-93; two-thirds were over 45 years of age at first endoscopy. A quarter of all patients who had been endoscoped had consistently normal examinations. Peptic oesophageal pathology was the commonest positive finding. A quarter of those prescribed ASDs between 1989 and 1993 had been endoscoped between 1978 and 1993. In those with a peptic diagnosis prescribed any ASD, the pathologies found were: oesophageal (42.9%), duodenal (36.3%) and gastro-pyloric (21.3%). Patients prescribed omeprazole were more likely to have undergone endoscopy than those prescribed other ASDs, and they were also more likely to have peptic oesophageal pathology. Long-term prescribing (>56 days per year) occurred in two-thirds of patients prescribed ASDs and 40% had at least one endoscopy. In those prescribed short-term ASDs, 20% had undergone at least one endoscopy. Peptic and nonpeptic endoscopic pathology was associated with increased ASD prescribing, but a normal endoscopy did not reduce prescribing. CONCLUSION: ASD prescribing appeared to be mainly symptom-driven. Positive endoscopic findings increased the prescribing of ASDs, but normal findings did not reduce it.

Aged↗
PubMed1999

Lack of effect of a 60 Hz magnetic field on biomarkers of tumor promotion in the skin of SENCAR mice.

It has been proposed that extremely low frequency magnetic fields may enhance tumorigenesis through a co-promotional mechanism. This hypothesis has been further tested using the two-stage model of mouse skin carcinogenesis, i.e. 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of skin carcinogenesis in mice initiated by a single subcarcinogenic dose of 7,12-dimethylbenz[a]anthracene. Experimentation utilized three different doses of TPA within its dose-response range (0.85, 1.70 or 3.40 nmol) and examined the following early biomarkers of tumor promotion after 1, 2 and 5 weeks of promotion: increases in epidermal thickness and the labeling index of epidermal cells, induction of epidermal ornithine decarboxylase activity and down-regulation of epidermal protein kinase C activity. Mice exposed to a 60 Hz magnetic field having a flux density of 2 mT for 6 h/day for 5 days/week were compared with mice exposed to an ambient magnetic field. Within the sensitivity limits of the biomarker methodology and the exposure parameters employed, no consistent, statistically significant effects indicative of promotion or co-promotion by the magnetic field were demonstrated.

Animals↗
PubMed1998

Altered p53 is associated with aggressive behavior of chondrosarcoma: a long term follow-up study.

BACKGROUND: p53 is a major tumor suppressor gene that has been implicated in the biology of a variety of human neoplasms, including some that affect the skeleton. Recent studies based on small numbers of cases have shown that overexpression or alteration of the p53 gene is frequently present in high grade, clinically aggressive chondrosarcomas of bone. In this study, the authors addressed the relation between overexpression and alteration of the p53 gene and the clinical aggressiveness of chondrosarcoma in a large series of patients for whom long term follow-up data were available. METHODS: The authors analyzed the expression and/or alteration of the p53 gene in 158 cases of chondrosarcoma of bone using immunohistochemistry, single-strand conformation polymorphism, and direct sequencing. They then related the findings to various clinicopathologic parameters and long term follow-up data. RESULTS: The presence of overexpression and/or structural alterations of the p53 gene was documented in 38.1% of chondrosarcomas of bone. A statistically significant correlation was observed between overexpression or alteration of the p53 gene and both the histologic grade of the tumor and the presence of metastasis. The probability of local recurrence free, metastasis free, and overall survival was significantly higher for patients with no overexpression or alteration of p53 than for patients with p53 overexpression or alteration. CONCLUSIONS: Overexpression or alteration of the p53 gene is an important predictor of aggressive clinical behavior in chondrosarcoma of bone.

Adolescent↗
PubMed1998

A morphometric analysis of glomerular and tubular alterations following fast-neutron irradiation of the pig and monkey kidney.

PURPOSE: The morphologic responses of the pig and monkey kidney to fractionated fast-neutron irradiation were assessed. METHODS AND MATERIALS: The right kidney of approximately 14-week-old female Large White pigs was irradiated with 6.6-12.2 Gy of fast neutrons (42 MeVd-->Be) given as 12 fractions over 18 days; the left kidney served as the contralateral unirradiated kidney. Both kidneys were removed at necropsy 2 years postirradiation. In addition, the remaining hypertrophied kidney of four unilaterally nephrectomized adult rhesus monkeys was irradiated with a total dose of 11.0 Gy fast neutrons (45 MeVp-->Be) given in an identical fractionation regimen to that used in the pig studies. These kidneys were removed when the animals exhibited renal failure, between 32-94 weeks postirradiation. Glomeruli were assessed for the presence of pathologic features, including intercapillary eosinophilic material (ICE), ectatic capillaries, thrombi, hemorrhage, and sclerosis. The relative proportion of renal cortex occupied by glomeruli, interstitium, normal, or abnormal tubules was determined using a Chalkley point grid. RESULTS: The incidence of normal glomeruli, ectatic capillaries, thrombosis, and periglomerular fibrosis were significantly different in the irradiated pig kidneys compared with the unirradiated contralateral kidneys (p < or = 0.02). Linear regression analysis demonstrated a significant dose relationship in terms of normal glomeruli, ectatic capillaries, and ICE (r > or = 0.64; p < or = 0.04). Irradiation was also associated with a significant (p < 0.0001) decrease and increase in the volume of renal cortex occupied by normal and abnormal tubules, respectively. Similar morphometric changes were noted in the irradiated monkey kidneys. CONCLUSIONS: The morphologic changes seen in the pig and monkey kidney after fractionated irradiation with fast neutrons are similar to those previously noted after single-dose or fractionated-photon irradiation. These findings support the hypothesis that the development of radiation nephropathy in these various models involves common pathophysiological mechanisms.

Animals↗
PubMed1998

Papillomas at high risk for malignant progression arising both early and late during two-stage carcinogenesis in SENCAR mice.

The current study was designed to further establish that most papillomas produced in SENCAR mice during two-stage skin carcinogenesis are, in fact, premalignant lesions and to specifically determine the malignant conversion potential of papillomas that arise at different times during the carcinogenesis process. A method was established to physically map and monitor the lifespan of all papillomas produced in SENCAR mice during the course of an initiation-promotion experiment using DMBA as the initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter. The results from these experiments showed that in groups of mice initiated with either 0.5 or 2.0 microg DMBA, long-term (60 weeks) treatment with TPA yielded a significantly higher number of SCCs compared to short-term treatment (7 weeks). Papillomas that emerged after 11 weeks and thereafter in all treatment groups had the ability to progress to SCCs. The median conversion time for all papillomas in all groups was 26 weeks. When corrected for median conversion time, papillomas that emerged in week 11 and thereafter in all treatment groups had similar or greater conversion ratios compared to those that emerged within the first 10 weeks. Interestingly, the median conversion time was significantly shorter (18 versus 27 weeks, respectively; P<0.0002) for papillomas that emerged in week 11 and thereafter compared to those that emerged at or prior to 10 weeks for all groups. The data in this study demonstrate that papillomas arising throughout a two-stage carcinogenesis protocol in SENCAR mice progress to SCCs. Many papillomas that arise later in two-stage carcinogenesis protocols do not have sufficient time to allow for conversion and should be excluded from the analyses. Furthermore, another novel finding of the current study was the observation that papillomas arising later in the two-stage protocol (>11 weeks) progressed to SCCs at a faster rate than those that arose earliest in the protocol.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

Lack of a co-promoting effect of a 60 Hz magnetic field on skin tumorigenesis in SENCAR mice.

It has been proposed that extremely low frequency (ELF) magnetic fields may enhance tumorigenesis through a co-promotional mechanism. This hypothesis has been further tested using the two-stage model of mouse skin carcinogenesis, i.e. 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of skin tumors in mice initiated by a single subcarcinogenic dose of 7,12-dimethylbenz[a]anthracene. Experimentation described herein utilized the SENCAR mouse and examined the effect of a magnetic field on skin tumor promotion induced by three different doses of TPA within its dose-response range, i.e. 0.85, 1.70 or 3.40 nmol, administered twice per week. SENCAR mice (56/treatment group) were exposed to a 60 Hz magnetic field having a flux density of 2 mT for 6 h/day for 5 days/week and compared with mice exposed to the ambient magnetic field. Tumor incidence and multiplicity were monitored weekly for 23 weeks of TPA promotion. Statistical evaluation of the effects of the magnetic field on tumor incidence and multiplicity did not reveal any statistically significant effects; thus, within the sensitivity limits imposed by the animal model and the exposure parameters employed, no promotional or co-promotional effect of a 2 mT magnetic field on skin tumor development in SENCAR mice could be demonstrated.

Animals↗
PubMed1998

Evaluation of helical computed tomography scan parameters for vascular imaging.

Helical x-ray computed tomography (hCT) is the volume acquisition of image data in which the data set represents a series of projections obtained in a helical spatial distribution. Data acquisition times and spatial resolution are determined largely by two user defined parameters--collimation and pitch. Each combination of pitch and collimation results in a slice profile which can be considered as the apparent slice thickness. Careful selection of pitch and collimation allows the acquisition of up to 20 cm of axial data in a breathold or first pass of bolus contrast material. This makes helical CT an excellent technique for angiographic (CTA) studies. Additionally, slices can be reconstructed at any interval to reduce partial volume averaging, minimizing the beading artifacts seen in maximum intensity projections (MIP) when interslice resolution is poor. We have evaluated a range of collimation and pitches for clinical CTA. Additionally, three reconstruction filters were included to determine the optimal frequency (spatial) properties for these techniques. Objective and subjective analyses were performed. We found pitches of up to 1.5:1 to be acceptable for all collimations. For a given scan length (z direction), selection of thinner collimation and higher pitch resulted in better SNR and observer scoring for angiographic presentations.

Angiography↗
PubMed1998

Prostate specific antigen and pathological features of prostate cancer in black and white patients: a comparative study based on radical prostatectomy specimens.

PURPOSE: We compared the relationship of pathological features and preoperative prostate specific antigen (PSA) levels of a consecutive series of black patients to a stage matched cohort of white patients treated during the same period. MATERIALS AND METHODS: The radical prostatectomy specimens of 40 black patients were reviewed and tumor volume was determined. Histopathological features (stage, grade, zonal distribution of cancer foci), tumor volume and prostate weight were correlated to pretreatment serum PSA levels. These parameters were compared with those of 148 white patients matched by pathological stage. RESULTS: Black patients exhibited a significantly higher incidence of seminal vesicle involvement (p=0.03) and cancers with a Gleason score of 8 or more (p=0.02), and a trend toward decreased pathologically organ confined, margin negative disease (40% black versus 53% white men, p=0.13). Although the incidences of multifocal cancer were virtually identical (90 and 82%) in the 2 groups, black patients exhibited a higher incidence of transition zone cancer foci (p <0.001). Mean prostate tumor volume, total gland weight and serum PSA level among black and white patients with pathological stage pT2-, pT2+ and pT3- cancer were not significantly different. However, with advancing pathological stage (pT3+ and pT3c) disease black patients had higher preoperative serum PSA levels on univariate and multivariate analyses despite similar total gland weight and tumor volume. CONCLUSIONS: Black patients who underwent radical prostatectomy often exhibited adverse pathological features. Two novel findings were that the distribution of cancer foci within the prostate was significantly different between black and white patients, and that serum PSA levels in patients with locally advanced prostate cancer were higher in black than in white men, despite adjustment for known variables affecting PSA. These observations suggest that differences in the biology of prostate cancer between these 2 races may exist.

Analysis of Variance↗
PubMed1997

Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer.

BACKGROUND: Thrombocytopenia is frequently encountered in patients with cancer. It is associated with an increased risk for clinically important bleeding episodes, which increases the demand for platelet transfusion. OBJECTIVE: To assess hematopoietic response to and clinical tolerance of recombinant human thrombopoietin, a recently cloned novel cytokine. DESIGN: Phase I and II clinical cohort study. SETTING: The University of Texas M.D. Anderson Cancer Center, Houston, Texas. PATIENTS: 12 patients with sarcoma who had high risk for severe chemotherapy-induced thrombocytopenia. INTERVENTION: A single intravenous dose of thrombopoietin (0.3 to 2.4 micrograms/kg of body weight) 3 weeks before chemotherapy. MEASUREMENTS: Peripheral blood and bone marrow evaluation before and after thrombopoietin administration. RESULTS: A single dose of thrombopoietin was associated with an increase in platelet counts (mean increase from baseline, 61% to 213%; P = 0.002) in a dose-related manner. This increase began by day 4 in most patients and peaked on a median of day 12. This sustained response was associated with a prolonged serum thrombopoietin half life (20 to 30 hours). The platelets appeared morphologically normal and showed normal aggregation in response to various agonists. Platelet response was accompanied by a dose-related increase in bone marrow megakaryocytes (as much as 4-fold); the expansion of the bone marrow progenitors of myeloid, erythroid, multipotential, and megakaryocytic lineages; and the marked mobilization of progenitors (maximum, 5.7-fold to 10-fold) of multiple cell lineages in the peripheral blood. Treatment was well tolerated, and no serious adverse events occurred. CONCLUSIONS: Thrombopoietin, administered as a single dose, is a potent stimulus for prolonged platelet production in humans. It merits further evaluation for the prevention and treatment of thrombocytopenia.

Antibodies↗