Search PubMed⌕ Search

Biomedical subjects

D R Smith

Publications and source records attributed to D R Smith.

At least 145 records · Page 8Linked to original sources
PubMed1996

Thelazia californiensis conjunctival infestation.

There are few reports of Thelazia californiensis infestation in humans in the literature. The authors report the clinical and histopathologic features of two patients who presented with symptoms of a mild unilateral chronic conjunctivitis from infestation by this parasite. In each case, the symptoms resolved immediately after removal of the worms. These are the first two patients from the Rocky Mountain area to be described with an infection from this particular worm. T. californiensis should be included in the differential diagnosis of patients with chronic conjunctivitis following hiking or camping in the mountains or back-country.

Adult↗
PubMed1996

Overexpression of the c-myc proto-oncogene in colorectal carcinoma is associated with a reduced mortality that is abrogated by point mutation of the p53 tumor suppressor gene.

The survival of 119 colorectal cancer patients was analyzed in the light of the overexpression status of the c-myc proto-oncogene mRNA and the point mutation status of the p53 tumor suppressor gene in the primary adenocarcinoma. The presence of >3 fold overexpression of c-myc mRNA in the primary tumor was found to be associated with a better prognosis than patients who evinced no overexpression (P = 0.02, log rank analysis). Point mutation of the p53 tumor suppressor gene was found to be associated with a poorer patient prognosis (P = 0.007, log rank analysis). Endogenous levels of c-myc and point mutation of p53 both contributed independently toward a poorer patient prognosis in Cox regression modeling. The better prognosis seen in patients who overexpress c-myc was offset when c-myc overexpression was coupled with a point mutated p53 gene. These results suggest that in colorectal adenocarcinoma c-myc deregulation leads to increased apoptotic death, but that this response may be modulated by a more downstream event such as point mutation of the p53 gene.

Adult↗
PubMed1995

Lead-binding proteins in brain tissue of environmentally lead-exposed humans.

This study reports the partial purification and characterization of cytosolic lead binding proteins (PbBPs) in human brain tissue of environmentally Pb-exposed subjects. The isolated proteins were initially characterized based upon the presence of endogenously associated Pb. Following partial purification (Sephadex G-75 and A-25 DEAE anion-exchange chromatography), the isolated PbBPs (contained within a single DEAE peak) showed a single class of high affinity binding sites with an apparent Kd of 10(-9) M, based upon competition assays using radioactive 203Pb and Hill and Scatchard analysis. The presence of endogenously bound Pb with the isolated proteins indicated the association of Pb with the protein(s) in vivo in these environmentally Pb-exposed subjects, since the samples were prepared in an ultraclean lead analysis laboratory. Moreover, the persistence of Pb-protein binding throughout the initial two steps (Sephadex G-75 and A-25 DEAE) of the purification scheme is consistent with the high affinity and stability of binding measured with the radiolead competition assays. The DEAE isolated PbBPs were further purified by denaturing reversed-phase HPLC analysis, resulting in the isolation of two proteins, thymosin beta 4 (5 kDa, pI 5.1) and a second as yet unidentified protein with an approximate molecular mass of 20 kDa and a pI of 5.9. Qualitative 203Pb-binding analysis of these HPLC purified proteins suggested that they may be primarily responsible for the observed Pb binding in the single DEAE peak. Nearly identical results were obtained in brain cytosols from male and female, and young and adult individuals, although further quantitative analyses are needed to investigate possible sex and age relationships. These data are significant because they contribute to a better understanding of the presence of PbBPs in a sensitive target organ for Pb toxicity in humans, suggesting a possible role of these or similar proteins as sensitive biomarkers of Pb exposure and toxicity.

Adult↗
PubMed1995

p53 point mutation and survival in colorectal cancer patients.

We have examined the relationship between point mutation of the p53 tumor suppressor gene and survival in colorectal cancer patients. We found that patients with tumors harboring mutated p53 genes showed a significantly poorer prognosis than did those patients with genes without point mutations, and, moreover, patient response to postoperative therapies depended significantly on mutation status in both adjuvant and palliative treatment cohorts. However, not all point mutations were the same functionally; point mutations within the conserved domains of the p53 tumor suppressor gene were inherently more aggressive than tumors with point mutations outside of these domains, and mutations of codon 175 were particularly aggressive. These results suggest that knowledge of a patient's p53 status, both with respect to the presence of point mutations and to the specific nature of the lesion, may be required to accurately predict both the course of the disease and the response of the disease to postoperative therapeutic interventions, especially those therapies based on the induction of apoptosis in the neoplastic cell.

Adenocarcinoma↗
PubMed1995

Genomic organization of the mycobacterial sigma gene cluster.

We have previously described sigma A and sigma B and their structural genes, mysA and mysB, respectively, in Mycobacterium smegmatis. We have now sequenced the corresponding regions in the M. tuberculosis and M. leprae chromosomes, and have found the two homologous genes. The chromosomal linkage and the deduced amino acid (aa) sequences of the two genes show very high similarity in the three species of mycobacteria. We also report the finding of two other open reading frames (ORF) in these clusters. orfX, which has an unknown function, is located between mysA and mysB. The other ORF, located downstream from mysB, encodes a homolog of DtxR, the iron regulatory protein from Corynebacterium diphtheriae (Cd).

Amino Acid Sequence↗
PubMed1995

Increased mRNA expression of the receptor-like protein tyrosine phosphatase alpha in late stage colon carcinomas.

The protein tyrosine phosphatase alpha (PTP alpha) mRNA level in paired samples of late stage (Dukes' D) colorectal tumors and adjacent normal colon mucosa was quantified by RNase protection assays. After normalization against 18S RNA or beta-actin mRNA level, a 2-10-fold increase in PTP alpha mRNA was detected in 10 of 14 tumors (approximately 70%) compared to mucosa. In situ hybridization of digoxigenin-labelled antisense PTP alpha RNA to tumor and mucosa sections produced a signal only in neoplastic cells of the tumor sample, consistent with the high increase in PTP alpha mRNA detected by RNase protection assays of some of the tumors. This is the first report suggesting an association of a protein tyrosine phosphatase with colorectal carcinoma. PTP alpha is a receptor-like PTP thought to be involved in regulating cell proliferation. Its oncogenic properties when overexpressed in cultured fibroblasts suggest that PTP alpha overexpression could contribute to the tumorigenic process in colon carcinoma.

Adenocarcinoma↗
PubMed1995

Measurements of environmental lead contamination and human exposure.

The importance of accurate measurements of environmental lead exposure and toxicity is substantiated by analyses documenting the global contamination of the biosphere with industrial lead and the pervasiveness of measurable lead toxicity in human populations. Those data demonstrating environmental lead contamination and toxicity have, in part, led to regulations that limit the amount of lead in some products (e.g., paint, solder, and gasolines) in many industrialized countries. These regulations have resulted in a substantial reduction in some lead discharges to the environment. In spite of these reductions, current environmental lead levels are still often more than 10-fold, and sometimes more than 10,000-fold, higher than natural levels. Further, environmental lead concentrations are expected to remain elevated for a protracted period due to continued emissions of relatively large amounts of industrial lead to the environment and the persistence of contaminant lead in the environment. Discharges of contaminant lead have resulted in increases in organism and human lead levels comparable to increases documented in environmental matrices, as indicated by a recent estimate of the natural level of lead in blood of preindustrial humans (0.016 microgram/dL or 0.8 nM). This estimate is 175-fold lower than average blood lead levels in the United States (2.8 micrograms/dL or 140 nM) and 600-fold lower than the recently (1991) revised Centers for Disease Control (CDC) action level of concern for early toxic effects in children (10 micrograms/dL or 480 nM). The significance of these comparisons to public health is corroborated by numerous studies suggesting that there may be no lower threshold for sublethal toxicity in contemporary (i.e., lead-contaminated) humans. Those data also indicate that environmental lead concentrations that were previously considered innocuous may be deleterious to human health. It is apparent that the extent of sublethal lead toxicity in humans may be best addressed by studies that consider control populations possessing natural (i.e., preindustrial) lead burdens, as well as state-of-the-art, trace-metal-clean techniques and advanced instrumentation. Trace-metal-clean techniques are required to prevent the inadvertent lead contamination of samples, which has plagued many previous analyses of environmental and human lead levels. Advanced instrumentation is required to provide the sensitivity, accuracy, and precision that are needed to quantify the sublethal effects of lead concentrations at environmental levels of exposure. Fortunately, methodologies utilizing these advancements are now capable of addressing many of the important issues (e.g., lead biomolecular speciation, low exposure effects) in environmental and human lead toxicology.

Environmental Pollutants↗
PubMed1995

Postmortem diffusion of alcohol from the stomach.

We explored postmortem ethanol diffusion from the stomach using a human cadaver model with multiple blood site sampling. In all, 400 ml of alcohol solution (5%, 10%, 20%, or 40% methanol and ethanol weight/volume in water) was introduced into the stomach by oesophageal tube. Blood methanol concentrations correlated with ethanol concentrations (methanol range, 1-676 mg%; ethanol range, 1-531 mg%; r = 0.9973). The pattern of ethanol diffusion showed marked between-case variability. Typically, concentrations were highest in pericardial fluid and, in decreasing order, in left pulmonary vein, aorta, left heart, pulmonary artery, superior vena cava, inferior vena cava, right heart, right pulmonary vein, and femoral vein. Diffusional flux was broadly proportional to the concentration of ethanol used. It was time-dependent (as assessed by 24-h and 48-h sampling) and markedly inhibited by refrigeration at 4 degrees C. After gastric instillation of 400 ml of 5% solution for 48 h at room temperature in paired cadavers, ethanol concentrations (mg%) were as follows: pericardial fluid 135, 222; aorta 50, 68; left heart 77, 26; right heart 41, 28; femoral vein 0. Using a 10% solution, ethanol concentrations (mg%) were as follows: pericardial fluid 401, 255; aorta 129, 134; left heart 61, 93; right heart 31, 41; femoral vein 5, 7. Introducing 50 ml of 10% alcohol solution into the oesophagus after oesophagogastric junction ligation produced similar aortic blood ethanol concentrations. This suggests that postmortem gastrooesophageal reflux and diffusion from the oesophagus is the mechanism of artefactual elevation of aortic blood ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta↗
PubMed1995

Isolation of coronaviruses antigenically indistinguishable from bovine coronavirus from wild ruminants with diarrhea.

Diarrheal feces from three sambar deer and one waterbuck in a wild animal habitat and one white-tailed deer on a wildlife farm in Ohio contained coronavirus particles which were agglutinated by antiserum to bovine coronavirus (BCV) in immune electron microscopy. Three coronavirus strains were isolated in human rectal tumor cells from the feces of the sambar and white-tailed deer and the waterbuck, respectively. Hemagglutination, receptor-destroying enzyme activity, indirect immunofluorescence, hemagglutination inhibition, virus neutralization, and Western blot (immunoblot) tests showed close biological and antigenic relationships among the isolates and with selected BCV strains. Gnotobiotic and colostrum-deprived calves inoculated with each of these isolates developed diarrhea and shed coronavirus in their feces and from their nasal passages. In a serological survey of coronavirus infections among wild deer, 8.7 and 6.6% of sera from mule deer in Wyoming and from white-tailed deer in Ohio, respectively, were seropositive against both of the isolates and selected BCV isolates by indirect immunofluorescence tests. These results confirm the existence of coronaviruses in wild ruminants and suggest that these species may harbor coronavirus strains transmissible to cattle.

Animals↗
PubMed1995

Increased interleukin-1 receptor antagonist in idiopathic pulmonary fibrosis. A compartmental analysis.

Idiopathic pulmonary fibrosis (IPF) is a poorly understood interstitial disease that usually proves refractory to therapy and results in irreversible tissue scarring and pulmonary dysfunction. Previous investigations have suggested a number of possible mediators of inflammation and fibrosis that typify IPF. We report increases in lung interleukin-1 receptor antagonist protein (IRAP) content in patients with IPF, as compared with normal control subjects. Importantly, this increase in IRAP was not accompanied by concomitant increases in interleukin-1 beta (IL-1 beta), resulting in a local environment that may be profibrotic. Tissue homogenates and bronchoalveolar lavage fluid from patients with IPF both demonstrate elevated IRAP content compared with that in normal subjects. Immunohistochemical staining and in situ hybridization localize IRAP to hyperplastic type II pneumocytes, macrophages, and local stromal cells. Finally, in vitro studies utilizing fibroblasts isolated from patients with IPF demonstrated no difference in constitutive IRAP production compared with that in normal subjects, but they revealed an exaggerated response to stimulation with transforming growth factor-beta (TGF-beta). These findings suggest that the fibrotic tissue changes of IPF and possibly other chronic interstitial lung diseases may result in part from the local effects of IRAP, and they also demonstrate that pulmonary nonimmune cells may influence local tissue changes through the elaboration of IRAP.

Bronchoalveolar Lavage Fluid↗
PubMed1995

Change: still an enigma to be faced.

Industries may have closed, but the real problem to be faced today is the attitude of the worker, employed and unemployed. They caused all their own problems. It has been more than 10 years since the manufacturing base began to erode. Can anyone still fear change? Where do the dislocated worker and the downsizing firm stand in relationship to the future?

Attitude↗
PubMed1995

Les Nouveaux Miserables: modern victims of social asphyxia.

During the past 30 years, social and economic barriers to health care services have increased for many Americans, especially for the nation's most vulnerable populations. Health status actually has declined for certain populations during this time. Meanwhile, national attention has been focused primarily on containing health care costs and on devising strategies for reforming the financing of health care rather than strategies for achieving improvements in the health status of the population. Existing methods of financing health care services, health research priorities, the increasing centralization and compartmentalization of health care services, and the recent failure of national health reform all serve to hinder this nation's progress towards developing a comprehensive and accountable health care system focused on promoting and achieving improved health as well as treating sickness. Recent changes in the health care marketplace, however, including a growing movement toward measuring the outcomes of medical treatments and an emphasis on improving the quality of services, have increased interest among payers and providers of health care services in investing in preventive services. Health maintenance organizations and other integrated health care delivery systems are beginning to devise incentives for increasing preventive care as well as for containing costs. The transformation of the nation's current medical care system into a true health care system will require innovative strategies designed to merge the existing fragmented array of services into coordinated and comprehensive systems for delivering primary and preventive health care services in community settings. The Community-Oriented Primary Care concept successfully blends these functions and has achieved measurable results in reducing health care costs and improving access to preventive services for identified populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Health Care Costs↗
PubMed1995

Association of activated proto-oncogenes ras and myc in colorectal carcinomas.

We have examined 60 colorectal carcinomas for activation of two proto-oncogenes, c-myc and c-Ki-ras. Over-expression of c-myc mRNA as determined by Northern analysis was found in 58% of cases (35/60). Activation of the c-Ki-ras gene by point mutations in codons 12 or 13 as determined by mismatch specific oligonucleotide hybridisation was found in 35% (21/60) of cases. There was a statistically significant association between activation of c-Ki-ras and over-expression of c-myc (P = 0.03), with 76% of tumours with an activated c-Ki-ras proto-oncogene showing over-expression of c-myc. The association was significant in left-sided colorectal tumours (P = 0.03) but not right-sided (P = 0.5). However, whereas only 59% of left side tumours showed at least one of the two changes (ras activation only, or myc activation only or both), 93% of right side tumours showed at least one of the changes (P = 0.01). Twenty-two percent of left side tumours showed both changes compared with 35% of right side tumours, although this result did not achieve significance (P = 0.2). These results suggest that in left-sided colorectal tumours ras and myc cooperate, as established in vitro, to produce neoplastic transformation while different pathway(s) are involved in right-sided tumours.

Base Sequence↗
PubMed1995

Allelic loss of the p53 gene in colorectal cancer.

The loss of specific chromosomal loci in cancers is indicative that the region contains a tumour suppressor gene. Allelic loss of chromosome 17p has been shown to occur in a wide variety of cancers such as lung, breast, colon, ovary and brain and, until recently, the gene believed to be involved was the p53 tumour suppressor gene. However, more recent studies have shown that the area deleted in some of these tumours does not include the structural gene for p53. For this reason it has been proposed that a tumour suppressor gene lying distal to p53 on chromosome 17p is the gene deleted in these cancers. As chromosome 17p has been shown to be deleted in approximately 75% of colorectal cancers, we set out to determine whether the target gene of these deletions was the structural gene for p53. Allelic loss was assessed by using restriction fragment length polymorphisms in 52 tumours. Deletions distal to p53 on chromosome 17p were assessed using the probe YNZ22.1 and allelic loss of p53 was assessed using probe pR4-2, a cDNA probe specific for the p53 gene. Out of the 21 tumours informative for both probes, 3 cases showed no allelic deletion of the chromosome 17p, 2 cases showed allelic deletion not encompassing the p53 gene and 16 cases (89%) showed allelic deletion including the p53 gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1995

Pericarditis following blunt thoracic trauma.

Pericarditis is a common clinical entity which has been reported frequently in association with numerous disease processes. However, pericarditis following blunt thoracic trauma is exceedingly rare and difficult to diagnosis. An 18 year-old female was transferred to UAB Hospital for evaluation and management of multiple injuries following a high-speed single-vehicle motor vehicle accident. Injuries included a fractured right tibia and femur, pelvic fracture, and a right pulmonary contusion with rib fractures. Orthopedic procedures were performed. Ventilatory support was provided due to a severe pulmonary contusion. The post-operative course was unremarkable. The patient was discharged two weeks after admission. One week after discharge, the patient was readmitted with pleuritic chest pain of several days duration. Diagnostic studies were performed. The patient was successfully treated with non-steroidal anti-inflammatory medications for pericarditis. Dramatic improvement ensured over two days. Follow-up showed no recurrence of pericardial symptoms, pleural effusion, or chest pain. In retrospect, complaints of episodic chest pain which were felt to be clinically insignificant during admission, may have been early signs of posttraumatic pericarditis secondary to blunt thoracic trauma.

Accidents, Traffic↗
PubMed1995

The presymptomatic molecular diagnosis of familial adenomatous polyposis in Singapore.

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder which predisposes to the development of colorectal cancer. The adenomatous polyposis coli (APC) gene, mutation of which is responsible for FAP, has been localised to chromosome 5q21. Linkage studies using DNA markers have proven useful for presymptomatic diagnosis of at-risk individuals. We have examined 8 FAP families from the Singapore Polyposis Registry by using 4 linked and 2 intragenic DNA markers. Presymptomatic diagnosis could be made in 84% (37 of 44) of at-risk individuals. Among these presymptomatically diagnosed cases, positive prediction was made in 32% (12 of 37) whereas negative prediction was possible in 68% (25 of 37). As the accuracy of genetic diagnosis is high and the test reliable in most cases, the major impact of these tests will be the reduction of unnecessary anxiety and a significant reduction in the frequency of screening for at-risk individuals who are not carrying the affected gene.

Adenomatous Polyposis Coli↗
PubMed1994

p53 and behaviour of colorectal cancer.

The tumour suppressor gene p53 is altered in most colorectal tumours. We found that lymphatic dissemination was driven by the presence of mutated p53 whether or not the cell contained wild-type p53. In a total sample of 187 specimens, point mutation of the p53 gene occurred in 70% and 43% of cases with and without lymph-node involvement, respectively. By contrast, haematogenous dissemination was apparently the result of absent functional wild-type p53 (whether or not the cell contained mutated p53). These results are of potential importance in the prediction of the clinical behaviour of a tumour.

Colorectal Neoplasms↗