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Biomedical subjects

J C Steele

Publications and source records attributed to J C Steele.

At least 55 records · Page 3Linked to original sources
PubMed1990

Humoral assays of human sera to disrupted and nondisrupted epitopes of human papillomavirus type 1.

The use of different assay systems and the disparity in results obtained has meant that we have little understanding about the role played by the humoral response during human papillomavirus (HPV) infection. Human antibody responses have so far appeared to be largely directed against the major capsid protein, L1. This protein possesses both type-specific and type-common antigenic determinants but it is not known which of these is important in vivo during the natural course of infection. In this study humoral responses of 83 individuals to purified HPV 1 virions were tested in three types of antibody assay. Western blot analysis detected antibodies in only eight of the serum samples, whereas an enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation assay using nondisrupted HPV 1 virions showed positive antibody reactivities for 71 and 64 individuals, respectively. We suggest from these results that the humoral response to L1 is mainly directed against native conformational epitopes present on the whole HPV 1 particle and that type-common epitopes are not largely involved. This was further demonstrated by the fact that when samples were tested in the same ELISA system using disrupted HPV 1 virions as the antigen instead of whole virus particles, the number of positive sera was reduced to 9 out of 83. We further conclude that humoral assays using antigenic material pertaining to disrupted HPV epitopes are of limited use, at least in the case of HPV type 1. There were no obvious correlations between the antibody assay results and clinical histories of wart infection except that a lower number of positive serum reactivities were found among the group of individuals claiming to have no past history of HPV infection.

Adolescent↗
PubMed1990

2-Amino-3-(methylamino)-propanoic acid (BMAA) in cycad flour: an unlikely cause of amyotrophic lateral sclerosis and parkinsonism-dementia of Guam.

We conducted an investigation of the levels of the neurotoxin 2-amino-3-(methylamino)-propanoic acid (BMAA) in cycad flour. Analysis of 30 flour samples processed from the endosperm of Cycas circinalis seeds collected on Guam indicated that more than 87% of the total BMAA content was removed during processing. Furthermore, in 1/2 the samples almost all (greater than 99%) of the total BMAA was removed. We found no significant regional differences in the BMAA content of flour prepared from cycad seeds collected from several villages on Guam. Testing of different samples prepared by the same Chamorro woman over 2 years suggests that the washing procedure probably varies in thoroughness from preparation to preparation but is routinely efficient in removing at least 85% of the total BMAA from all batches. Analysis of a flour sample that had undergone only 24 hours of soaking indicated that this single wash removed 90% of the total BMAA. We conclude that processed cycad flour as prepared by the Chamorros of Guam and Rota contains extremely low levels of BMAA, which are in the order of only 0.005% by weight (mean values for all samples). Thus, even when cycad flour is a dietary staple and eaten regularly, it seems unlikely that these low levels could cause the delayed and widespread neurofibrillary degeneration of nerve cells observed in amyotrophic lateral sclerosis and the parkinsonism-dementia complex of Guam (ALS-PD).

Amino Acids, Diamino↗
PubMed1990

Sensitivity to ionising radiation of transformed human cells containing mutant ras genes.

Measurement of colony forming ability following exposure to gamma-rays has been performed on human retinoblasts transformed with either adenovirus 5 or 12 early region 1 DNA, adenovirus early region 1A plus activated N- or H-ras DNA or SV40 DNA. In contrast to recently reported results (M.D. Sklar, 1988, Science, 239, 645-647), we found no general correlation between transformation with activated ras and increased radiation resistance. Similarly, there was no correlation between D0 values and the level of expression of ras p21 in transformed human retinoblasts as determined by liquid competition assay. Indeed, cell lines with very similar D0 values had ras contents varying by up to one hundred fold. Cell lines transformed with SV40 DNA were generally less sensitive to ionising radiation than adenovirus and/or ras transformants, but even so the variation in sensitivity within these encompassed the whole spectrum of values obtained for the ras transformants. It may be interesting to note, however, that two out of the three ras transformants which were least sensitive to gamma-rays were cell lines expressing the highest levels of p21.

Adenovirus Early Proteins↗
PubMed1989

Fine-needle aspiration of subcutaneous phaeohyphomycosis caused by Wangiella dermatitidis.

Two cases of subcutaneous phaeohyphomycosis, first recognized by fine-needle aspiration (FNA), were confirmed with culture, excision, and histologic study. Both patients had debilitating medical problems and a solitary mass on the left leg. Pigmented hyphae and other fungal elements, numerous in both aspirates, assumed a variety of forms that did not permit specific identification. Culture grew Wangiella dermatitidis in both cases. FNA also yielded purulent exudate, multinucleated giant cells, and, in one case, epithelioid histiocytes. Both excised lesions were abscesses, with associated granulomatous inflammation, fibrosis, and plant splinters. Fungi in sections resembled those seen in the aspirates.

Biopsy, Needle↗
PubMed1989

A retinopathy on Guam with high prevalence in Lytico-Bodig.

A pigmentary retinopathy resembling that sometimes seen in posterior ophthalmomyiasis interna was found in 26 (53.1%) of 49 Chamorro patients from Guam who have Lytico-Bodig (also known as amyotrophic lateral sclerosis-Parkinsonism-dementia complex of Guam). In nine cases, the retinopathy was bilateral. Similar changes were found in 6 (16.2%) of 37 clinically normal individuals from southern villages on Guam that have a high incidence of Lytico-Bodig, and in 1 (3.1%) of 32 individuals from Saipan, an island north of Guam that has a low incidence of the disease. These results indicate the possibility of an association-between Lytico-Bodig and a retinopathy on Guam that may be parasitic in origin. Occurrence of a similar association in other debilitating diseases on Guam and frequency of occurrence of retinopathy in Guamanians with Lytico-Bodig after leaving Guam have yet to be determined.

Adult↗
PubMed1988

Supranuclear disturbances of ocular motility in Lytico-Bodig.

We found abnormal supranuclear ocular or lid motility in all of 37 patients with Lytico-Bodig (amyotrophic lateral sclerosis/parkinsonism-dementia complex). Twenty-one patients had pursuit paresis, 18 abnormal vestibulo-ocular reflex (VOR) cancellation, 15 abnormal convergence, 13 abnormal optokinetic nystagmus (OKN), 12 conjugate gaze limitation, nine nystagmus, nine saccadic paresis, and six abnormal fixation. Lid abnormalities included glabellar hyperreflexia in 21, involuntary levator inhibition in three, and blepharospasm in two. Earlier reports have indicated infrequent ocular disturbances in Lytico-Bodig, but we now find supranuclear eye and lid deficits are universal and sometimes very prominent.

Aged↗
PubMed1987

Observations about amyotrophic lateral sclerosis and the parkinsonism-dementia complex of Guam with regard to epidemiology and etiology.

For more than 150 years, Chamorro natives of the Mariana Islands in the Western Pacific Ocean, have developed fatal paralysis in middle and later life, which we term amyotrophic lateral sclerosis/parkinsonism-dementia (ALS/PD). The cause of the disease might be exposure to seeds of the indigenous cycad. Motor system disease is induced in cynomolgus monkeys by feeding them beta-N-methylamino-L-alanine (BMAA), an amino acid present in cycad seeds. We believe that the cycad seeds which usually cause no immediate adverse symptoms when prepared and eaten as flour, or applied topically as medicine, can give rise to widespread and severe nerve cell degeneration after a latency of many decades. Furthermore, it may be that only a single exposure to this potent but silent toxin(s) can result in fatal neurological disease years later.

Alzheimer Disease↗
PubMed1986

The effect of hyperlipoproteinemia on thrombolysis: in vitro studies using purified lipoproteins from normolipemic donors.

To determine whether or not lipoproteins affect thrombolysis in vitro using Chandler's loop method, VLDL, LDL, and HDL fractions from healthy male donors were obtained by ultracentrifugation. The lipoproteins were used to enrich whole blood or fibrin thrombi radiolabeled with 125-I-fibrinogen. Lipoprotein-enriched or unenriched thrombi were perfused in rotating Chandler loops with lipoprotein-enriched or unenriched plasma, respectively. Lysis was initiated by adding high molecular weight urokinase or single chain pro-urokinase to the perfusion medium. In some experiments, plasminogen was also added. Variation in the amounts of these activators and plasminogen permitted study of the effect of lipoproteins over a range of thrombolysis. No consistent statistically significant difference in the degree or time course of lysis of lipoprotein-enriched vs. unenriched thrombi or perfusion media was found. These studies, using normal lipoproteins, do not preclude the possibility that lipoproteins from patients with type IIa, IIb, or IV hyperlipoproteinemia may be genetically abnormal or may function pathologically, resulting in an effect on thrombolysis.

Adult↗
PubMed1986

Growth of four microorganisms in polyethylene glycol-electrolyte lavage solution.

The growth of Staphylococcus epidermidis, Serratia marcescens, Pseudomonas aeruginosa, and Candida albicans in reconstituted polyethylene glycol-electrolyte lavage solution (PEG-ELS) stored under refrigeration and at room temperature was studied. A standard inoculum of each organism was added to one of four 4-L containers (one organism per container). From each container 28 aliquots of 25-mL each were removed and stored under refrigeration or at room temperature. One container was not inoculated and served as a control. Duplicate aliquots of the inoculated and the control solutions were filtered and incubated for quantification of organisms on days 0, 1, 2, 4, 8, 16, and 30. Solutions stored at room temperature supported the growth of S. marcescens and Ps. aeruginosa. The counts of these organisms increased to approximately 10(6) colony-forming units (CFU)/mL over 16 days. The counts of Staph. epidermidis in solutions stored at room temperature increased slightly over the first 24 hours and declined steadily to zero after day 4. C. albicans reached a maximum colony count of 5.84 cfu/mL on day 16 and steadily declined to 0.92 cfu/mL on day 30. Solutions stored under refrigeration did not support the growth of any microorganisms. Microbial growth was not detected in any of the control solutions over the 30-day study period. The polyethylene glycol-electrolyte lavage solution studied here should be refrigerated after reconstitution to minimize microbial growth. This solution may be used for up to 30 days after reconstitution when it is stored under refrigeration.

Bacteria↗
PubMed1985

In-vitro activity of BMY 28142, a new aminothiazolyl cephalosporin.

The in-vitro activity of BMY 28142, a new alpha-methoxyimino aminothiazolyl cephalosporin, was determined by microdilution broth techniques. The agent demonstrated excellent activity against recent clinical Enterobacteriaceae isolates with a 90% minimum inhibitory concentration (MIC90) of 0.25 mg/l or less for all but one species tested. BMY 28142 inhibited all Pseudomonas aeruginosa strains tested (MIC90 = 8.0 mg/l) as well as most other non-fermentative bacteria studied. Methicillin-susceptible Staphylococcus aureus were susceptible to BMY 28142 with MIC90 = 4.0 mg/l, while methicillin-resistant strains were generally resistant (MIC range 8- greater than 32 mg/l).

Acinetobacter↗
PubMed1983

Lack of influence of commonly used drugs on bioassay indicator organisms.

Many commonly used pharmaceutical agents have been found to inhibit bacterial growth in vitro. Determinations of antimicrobial concentrations in sera of patients taking nonrecognized antibacterial agents could possibly be altered if bioassay systems are utilized for the determinations. We therefore attempted to determine the in vitro effect of commonly used drugs on bioassay indicator organisms. Fifty-one different agents (antihistamines, anticholinergics, central nervous system agents, cardiovascular agents, analgesics, steroids, muscle blockers, and other miscellaneous agents) were tested for inhibition or enhancement of the growth of Bacillus subtilis, Staphylococcus aureus, Micrococcus luteus, and Klebsiella pneumoniae. None of the agents tested exhibited any effect on standard in vitro bioassay organisms. Nortriptyline hydrochloride inhibited the growth of B. subtilis and M. luteus at a concentration of 500 micrograms/ml (zones of inhibition, 14 and 13 mm, respectively), but no inhibition was observed with concentrations of 50 micrograms/ml or lower.

Bacteria↗
PubMed1979

Characterization of the apolipoprotein B polypeptide of human plasma low density lipoprotein in detergent and denaturation solutions.

Apolipoprotein B, the polypeptide moiety of human serum low density lipoprotein, is subject to degradation (as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) both in the intact particle and after delipidation. Protease inhibitors, sodium azide, and nitrogen saturation did not influence the rate or degree of degradation. Lipid-free apolipoprotein B prepared by gel exclusion chromatography in sodium dodecyl sulfate bound a limited number of detergent molecules (up to 300) in monomeric sodium dodecyl sulfate solutions; circular dichroic spectra of this complex were similar to spectra of the intact lipoprotein. Near the critical micelle concentrations, a large, cooperative increase in detergent binding occurred, accompanied by circular dichroic changes indicating increased alpha helicity. By sucrose density centrifugation, lysopalmitoyl phosphatidylcholine could be substituted for the anionic detergent; about 300 mol of lysolipid were bound to the polypeptide. Replacement of detergent with guanidine hydrochloride by dialysis produced a soluble polypeptide with no ordered structure at denaturant concentrations above 7 M. At lower guanidine hydrochloride concentrations, structural elements were regained in a broad, reversible transition. It appears that apolipoprotein B is an easily degraded polypeptide with regions resembling water-soluble proteins but other regions which interact with lipid (or synthetic amphiphiles) and produce an overall insolubility in aqueous solution in the absence of amphiphilic ligands.

Apolipoproteins↗
PubMed1979

Molecular weight and hydrodynamic properties of apolipoprotein B in guanidine hydrochloride and sodium dodecyl sulfate solutions.

The apolipoprotein B polypeptide of human serum low density lipoprotein exists (after reduction of disulfide bonds) as a random coil with a molecular weight of 250,000 in concentrated solutions of guanidine hydrochloride. With intact disulfide bonds, there is a limited restraint on the polypeptide conformation in this denaturing solvent. In the presence of saturating amounts of bound sodium dodecyl sulfate, the apolipoprotein is dimeric and highly asymmetric. This work substantiates the monomeric molecular weight of 250,000 for apolipoprotein B reported by others (Smith, R., Dawson, J.R., and Tanford, C. (1972) J. Biol. Chem. 247, 3376-3381) and demonstrates that the dimeric state of the polypeptide extant in vivo is maintained in micellar detergent solution.

Apolipoproteins↗