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Biomedical subjects

D Peterson

Publications and source records attributed to D Peterson.

At least 127 records · Page 7Linked to original sources
PubMed1996

Free, complexed, and total serum prostate-specific antigen concentrations and their proportions in predicting stage, grade, and deoxyribonucleic acid ploidy in patients with adenocarcinoma of the prostate.

OBJECTIVES: Nearly half of men with clinically localized prostate cancer are understaged. We evaluated whether knowledge of preoperative free prostate-specific antigen (f-PSA), complexed (c-PSA), and total (t-PSA) concentrations or the ratios thereof (f-PSA/t-PSA, c-PSA/t-PSA, and f-PSA/c-PSA) could improve upon the staging of prostate cancer when compared with standard PSA testing (t-PSA). In addition, we examined their associations with tumor grade and deoxyribonucleic acid (DNA) ploidy. METHODS: Two hundred ninety patients with prostate cancer, 178 (61%) of whom were treated with radical prostatectomy, formed the study group. RESULTS: Although there were significant differences in the f-PSA concentrations with respect to clinical stage, considerable overlap in PSA levels among the clinical substages was observed. Statistically significant differences but weak correlations were observed between the individual f-PSA, c-PSA, and t-PSA concentrations with regard to pathologic stage (organ-confined versus extraprostatic) and grade. No significant relationship, however, was observed with the three ratios. Higher PSA values were not always associated with a pathologic stage of pT3 or greater, and lower levels did not ensure that a tumor was organ-confined. Only a slight association was observed between c-PSA and t-PSA levels and DNA ploidy. No significant relationship was observed between the f-PSA levels as well as the three ratios with regard to DNA ploidy. A statistically significant improvement in predicting pathologic stage was observed when combining knowledge of preoperative t-PSA concentration with the c-PSA/t-PSA ratio. However, the area under the receiver operator characteristic curves was only slightly increased; as such this combination was of limited clinical utility. CONCLUSIONS: Statistically significant but weak correlations were observed between the molecular forms of PSA and stage, grade, and DNA ploidy. The significant overlap in f-PSA and c-PSA values among all stages, grades, and ploidy values precluded any useful predictive information for the individual patient. As such, preoperative knowledge of f-PSA and c-PSA values and the three ratios provided no additional diagnostic information over standard PSA (t-PSA) values alone.

Adenocarcinoma↗
PubMed1996

Mutation rates at the glycophorin A and HPRT loci in uranium miners exposed to radon progeny.

OBJECTIVES: To find whether a relation exists between estimated levels of exposure to radon and its progeny and mutations in hypoxanthine phosphoribosyl transferase (HPRT) and glycophorin A in a cohort of former uranium miners. METHODS: A cohort study involving a sample of miners from the Radium Hill uranium mine in South Australia, which operated from 1952 to 1961. Radiation exposures underground at Radium Hill were estimated from historical radon gas measures with a job exposure matrix. Workers from the mine who worked exclusively above ground according to mine records were selected as controls. In 1991-2 miners were interviewed and blood taken for measurement of somatic mutations. Mutation rates for HPRT and glycophorin A were estimated with standard assay techniques. RESULTS: Homozygous mutations of glycophorin A were increased in underground miners (P = 0.0027) and the mutation rate tended to rise with increasing exposure with the exception of the highest exposure (> 10 working level months). However, there was no association between place of work and either the hemizygous mutations of glycophorin A or the HPRT mutation. CONCLUSIONS: There may be an association between glycophorin A mutations and previous occupational exposure to ionising radiation. However, not enough is known at present to use these assays as biomarkers for historical exposure in underground mining cohorts.

Biomarkers↗
PubMed1996

Hepatitis B virus core and e antigen: immune recognition and use as a vaccine carrier moiety.

The hepatitis B virus (HBV) core gene codes for two partially colinear antigens: a secreted antigen (HBeAg) and the particulate core antigen (HBcAg), which assembles to form subviral particles and in virions contains the viral genome and polymerase. In this review we summarize data on the immune recognition of HBc/eA and recent progress in the use of HBcAg as a carrier moiety for heterologous epitopes. During HBV infection, HBcAg and HBeAg are important targets of antiviral immunity. HBcAg and HBeAg are serologically distinct but share all characterized T-cell epitopes. The particulate HBcAg can elicit T-cell-independent as well as T-cell-dependent antibody responses, HBeAg is a strictly T-cell-dependent antigen. Neonatal tolerance to maternally derived circulating HBeAg may facilitate chronic HBV infection after vertical transmission of HBV. In a murine transgenic model, HBc/eAg-specific Th1 cells were more readily anergized, whereas Th2 cells more easily escaped tolerization. In human HBV infection, acute adult HBV infection with subsequent virus elimination was characterized by Th1-like alpha-HBV serum IgG subtype distribution, whereas a Th2-like distribution of IgG subtypes was observed during chronic infection. During chronic infection, core gene mutants which abolish HBeAg synthesis were frequently observed. To exploit the unusual immunogenicity of particulate HBcAg as a vaccine carrier moiety, insertion sites for foreign epitopes were defined in recombinant expression systems. While fusion of epitopes to the N-terminus required a linker sequence for surface accessibility, both fusion to the N-terminus and to the C-terminus was compatible with particle assembly and preserved the native antigenicity and immunogenicity of HBcAg. Epitope insertion at an immunodominant internal site of HBcAg reduced the HBcAg immunogenicity and antigenicity and most drastically enhanced the immunogenicity of the inserted foreign epitopes. This internal site of HBcAg was used to express circumsporozoite antigen (CS) repeat epitopes of two rodent malaria parasites and of Plasmodium falciparum. Purified hybrid HBcAg-CS proteins were particulate and displayed CS antigenicity as well as reduced native HBc antigenicity. Immunization of several mouse strains with HBcAg-CS hybrid particles resulted in high-titered serum anti-CS antibodies representing all murine IgG isotypes and protected BALB/c mice against plasmodial challenge. Immunization of mice with HBcAg or HBcAg-CS particles formulated on alum, complete Freund's or incomplete Freund's adjuvant resulted in equivalent anti-CS and anti-HBc serum antibody titers. Preexisting immunity to HBcAg did not significantly alter the immunogenicity of hybrid HBcAg particles suggesting that carrier-specific immune suppression does not limit the use of hybrid HBcAg with internal insertions. Immunization with HBcAg-CS particles universally primed HBcAg-specific T cells and in addition CS-specific T cells were if the insert contained a CS-specific T-cell site for the corresponding murine MHC class II haplotype. The internal amino acid position in HBcAg is therefore permissive for the inclusion of heterologous T-helper as well as B-cell epitopes.

Animals↗
PubMed1996

Use of an adjustable, transportable, radiolucent spinal immobilization device in the comprehensive management of cervical spine instability. Technical note.

In this report the authors describe a device that consists of a transportable, radiolucent board that couples to a standard halo head ring. The board provides continuous cervical spine immobilization during all phases of acute medical treatment of cervical spine instability, including closed reduction, transport, radiographic imaging, and operative procedures. By combining the advantages of several existing systems, this immobilization device facilitates and improves the safety of comprehensive acute management of cervical spinal instability by eliminating the need for patient transfer from stretcher to radiography machine to operating table. Its radiolucent construction and its compatibility with standard operating tables allow unencumbered surgical access and ample room for biplanar fluoroscopy, thereby also facilitating operative procedures, particularly the placement of internal spinal fixation.

Cervical Vertebrae↗
PubMed1996

Hybrid hepatitis B virus core antigen as a vaccine carrier moiety. II. Expression in avirulent Salmonella spp. for mucosal immunization.

Hepatitis B virus (HBV) core antigen (HBcAg) is a highly immunogenic subviral particle. We and others have defined insertion sites for heterologous epitopes and successfully used hybrid particles to generate B and T cell immunity (reviewed in: Schödel et al. 1994a, 1995). Here we shall review recent progress in constructing avirulent Salmonella spp. expressing hybrid HBcAg particles carrying different epitopes. Hybrid HBcAg particles carrying virus neutralizing epitopes of the hepatitis B virus pre-S region or repeat epitopes of plasmodial circumsporozoite antigens were previously described (Schödel et al. 1992, 1994b). Salmonella spp. can be attenuated by defined genetic means so that they become avirulent, yet preserve invasiveness after oral uptake. Hybrid HBcAg-pre-S particles were expressed in Salmonella typhimurium and S. typhi vaccine strains. A single oral immunization of mice with such live recombinant S. typhimurium strains elicited a high titered serum anti-pre-S1 IgG response. Similarly, circumsporozoite repeat epitopes of three different malaria parasites were expressed as HBcAg-CS hybrids in recombinant S. spp. and were found to be highly immunogenic after oral immunization. To analyze mucosal immune responses, BALB/c mice were immunized with recombinant phoPc S. typhimurium expressing HBcAg by various mucosal routes (Hopkins et al., 1995). All routes of immunization resulted in high titered serum and local antibodies against HBcAg and S. typhimurium LPS. However, nasal immunization was most efficient in generating pulmonary IgA and rectal immunization in eliciting rectal IgA, suggesting some compartmentalization of the mucosal immune response.

Administration, Oral↗
PubMed1996

Knowledge on collection and analysis of health information of state certified nurses from rural health centres, Masvingo Province.

OBJECTIVE: To assess the knowledge on collection and analysis of health information of State Certified Nurses (SCNs) from Rural Health Centres (RHCs), Masvingo Province. DESIGN: Three methods were employed during the assessment: a questionnaire, observation, and practical exercises (calculations). SETTINGS: 19 RHCs in Chiredzi and Bikita Districts, Masvingo Province. SUBJECTS: 19 SCNs in charge of Rural Health Centres. MAIN OUTCOME MEASURES: Ability to analyze and utilize health information, availability of graphs, master cards summaries (health diaries) and minutes. Presence or absence of catchment maps, charts on population breakdown and immunization coverage charts. Ability to calculate some rates and percentages. RESULTS: Of 19 SCNs in charge who said they do school health programmes, only six had any evidence that they do so; of nine SCNs in charge who reported that they have graphs on weekly reported diseases, only four had graphs displayed. Of 18 SCNs in charge who said they had immunization coverage targets only 11 had charts displayed; of 18 SCNs in charge who reported that they discuss health problems in their areas, only one had minutes documenting the discussion. Only six of 19 SCNs at rural centres could calculate coverage rates and only one of 19 SCNs at health centres could calculate dropout rates. CONCLUSION: Comparing the questionnaire responses with the findings from observations, it can be seen that more is reported than is actually done. From the practical exercises it was evident that the ability to do basic calculations was often lacking.

Data Collection↗
PubMed1996

Factors associated with human anthrax outbreak in the Chikupo and Ngandu villages of Murewa district in Mashonaland East Province, Zimbabwe.

OBJECTIVES: To determine factors associated with human anthrax. DESIGN: Unmatched restrospective case control. SETTING: General community of Chikupo and Ngandu villages of the Nyamutumbu area of Murewa district in Mashonaland East Province of Zimbabwe. SUBJECTS: 19 persons were identified using the clinical anthrax definition developed by the Centre for Diseases Control as cases, and 57 persons who reported not having taken antibiotics for anthrax were identified as controls. Both cases and controls had never been out of the village during the time of the epidemic. MAIN OUTCOME MEASURES: Percent of cases and controls handling, eating and drinking products of an alleged infected animal. RESULTS: Out of 19 cases of anthrax, five died, giving a case fatality rate of 26% (95% CI 5 to 47%). The following factors were significantly associated with the disease: skinning and cutting meat of an animal alleged to have shown symptoms of anthrax (OR 29, 95% CI 3 to 707, p < 0.001), eating contaminated meat (OR 20, 95% CI 2 to 470, p < 0.001), belonging to a religious sect which does not restrict its followers from eating meat from a carcass (OR 6, 95% CI 1 to 21, p = 0.003), handling contaminated meat in the process of selling it (OR 5, 95% CI 1 to 31, p = 0.033) and attending a gathering (OR 4, 95% CI 1 to 21, p = 0.028). CONCLUSIONS: Anthrax still remains endemic in Zimbabwe despite the public health and veterinary efforts to control the disease. Having knowledge of risk factors may help one to minimize chances of contracting anthrax.

Adult↗
PubMed1995

Synthesis and secretion of caseins by the mouse mammary gland: production and characterization of new polyclonal antibodies.

Polyclonal antibodies to mouse alpha- and beta/gamma-caseins were raised in rabbits. These antibodies display tissue- and species specificity as shown by immunoblotting. Immunohistochemical analyses demonstrate that both alpha- and beta/gamma-caseins were synthesized and secreted from virtually all lactating mammary epithelial cells, in a pattern very similar to that of the mouse alpha-lactalbumin. Residual amounts of caseins were located also in the apical surface of epithelial cells surrounding the ducal lumen of virgin mammary gland sections. In contrast to the significant level of gamma-casein in the milk, the amount of this protein compared to alpha- or beta-caseins was extremely low in medium conditioned for 24 h by mammary explants of mid-pregnant mice immediately after explantation or after 4 days.

Animals↗
PubMed1995

Class II cytoplasmic and transmembrane domains are not required for class II-mediated B cell spreading.

B cells cultured on immobilized anti-class II monoclonal antibody (mAb) change from round to flattened cells, with lamellipodia and filopodia. This change in cell morphology, termed 'spiders', occurs within 30 min upon culture and is mediated through either I-A or I-E molecules. Class II molecules that are defective in mediating protein kinase C (PKC) due to the deletions of both alpha and beta chain's cytoplasmic (Cy) domain sequences can induce spider formation. B-cell transfectants that express chimeric MHC class II/class I molecules, where the ectodomains are class II sequences and the transmembrane and Cy domains are class I sequences also form spiders when cultured on anti-class II mAb. The spider morphology is not induced by either anti-immunoglobulin (Ig) or anti-MHC class I mAb. Treatment of B cells to increase intracellular cAMP, a component of the class II signaling pathway also results in spider formation with the same kinetics and percent change in the responding population as that induced by anti-class II mAb. Cytochalasin A treatment which disrupts cytoskeletal actin filaments and the tyrosine kinase inhibitor, genistein, both inhibit spider formation. Actin redistributes from a concentric ring in round cells to the ends of the filopodia in the spiders. The mechanism of spider induction whether resultant from second messengers following class II signaling or from non-signaling-induced physical interactions of class II with intracellular cytoskeletal components only requires the extracellular domains of class II. The biologic relevance of B-cell spiders is currently not known but has been reported to be associated with class II signal transduction and efficient Ag presentation.

Actins↗
PubMed1995

A recombinant Salmonella typhimurium vaccine induces local immunity by four different routes of immunization.

Immunization of mice with an attenuated Salmonella typhimurium strain (Phopc) carrying a plasmid encoding a hybrid form of the hepatitis B virus core antigen (HBc) induced specific antibody responses against the bacterial lipopolysaccharide (LPS) and HBc. Different mucosal routes of immunization, i.e., oral, nasal, rectal, and vaginal, were compared for their ability to induce a systemic as well as a mucosal response at sites proximal or distant to the site of immunization. Anti-LPS and anti-HBc immunoglobulin A (IgA) antibodies were measured in saliva, in feces, and in genital, bronchial, and intestinal secretions. Specific antibodies in serum and secretions were observed after immunization via all routes; however, the response to LPS was independent of that against HBc. In serum, saliva, and genital and bronchial secretions, high amounts of anti-HBc IgA were obtained by the nasal route of immunization. Vaginal immunization resulted in two different responses in mice: high and low. We observed a correlation between the level of specific immune response and the estrous status of these mice at the time of immunization. Rectal immunization induced high amounts of IgA against HBc and LPS in colonorectal secretions and feces but not at distant sites. These data suggest that S. typhimurium is able to invade different mucosal tissues and induce long-lasting local IgA responses against itself and a carried antigen after a single immunization.

Animals↗
PubMed1995

Glycogen storage disease type Ia in two littermate Maltese puppies.

Glycogen storage disease type Ia (GSD-Ia) (von Gierke's disease) was identified in two 47-day-old littermate Maltese puppies. The puppies were presented for necropsy with a history of failure to thrive, mental depression, and poor body condition. Gross findings included small body size and emaciation (212 and 246 g versus 595 g for normal littermate), severely enlarged pale livers (48 and 61 g), and pale kidneys. Histologically, there was marked diffuse vacuolation of hepatocytes with large amounts of glycogen and small amounts of lipid. Renal tubular epithelium was mildly to moderately vacuolated. Soft tissue mineralization was present in renal tubules and pulmonary alveolar septa. Biochemical analysis showed that levels of glucose-6-phosphatase were markedly reduced in liver (0.3 and 0.4 microM/minute/g tissue versus 4.7 +/- 1.5 microM/minute/g tissue for controls) and kidney (0.45 and 0.4 microM/minute/g tissue versus 4.1 microM/minute/g tissue for controls) and that glycogen content was increased in liver (9.4% and 9.4% versus 1.3% +/- 1.4% for controls). This is the first confirmed report of animals with glycogen storage disease type Ia.

Animals↗