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Biomedical subjects

F D Miller

Publications and source records attributed to F D Miller.

At least 109 records · Page 6Linked to original sources

Tandem repeats of a specific alternating purine-pyrimidine DNA sequence adjacent to protamine genes in the rainbow trout that can exist in the Z form.

We have located an extensive (AC)n-rich but specific sequence downstream of three rainbow trout protamine genes. Although sharing considerable sequence homology, including a perfectly conserved 46 base pair repeat, the sequences exhibit a regular heterogeneity in the length of the (AC)n-rich tracts. Radioimmunoassay experiments, S1 nuclease sensitivity studies, two-dimensional electrophoretic analysis, and immunoelectron microscopy studies have been used to determine if the region could assume a Z DNA conformation. It was found that, in a supercoiled plasmid, the (AC)n-rich region has the ability to attain the Z DNA conformation under physiological conditions.

Animals↗

Assembly and characterization of nucleosomal cores on B- vs. Z-form DNA.

The ability of right- vs. left-handed alternating purine/pyrimidine copolymers to support the formation of nucleosomes has been examined by using a trout testis assembly factor. The protein, which is thermostable, has a molecular weight of 29000 and will assemble nucleosomes onto both SV40 and calf thymus DNA. This assembly factor has been used to assemble nucleosomes onto the B and Z conformations of poly[d(Gm5C)] and the B conformation of poly[d(GC)]. The isolated B-form particles, which sediment at approximately 11 S in a sucrose density gradient, contain DNA of 140-200 bases in length and the four core histones. The isolated Z-form particles, which also sediment at approximately 11 S, contain the four core histones and DNA of 170-250 bases in length. Physical analysis of the particles by absorbance and circular dichroic spectroscopy indicates that the DNA remains in the original conformation throughout the isolation procedure. Further, the particles reconstituted onto left-handed DNA compete effectively for an anti-Z DNA antibody, while the corresponding right-handed particles do not. Analytical sedimentation velocity determinations indicate that the B-form poly[d(Gm5C)] and poly[d(GC)] particles sediment at 11.2 and 11.1 S, respectively. In contrast, the poly[d(Gm5C)] Z-form particles have an S20,w of 10.6 S. The differences in the sedimentation velocity and the density of the cores, and in the lengths of DNA associated with the particles, suggest that the conformation of the DNA affects the manner in which it associates with the histone octamer.

Animals↗

Controlled trial of enviroxime against natural rhinovirus infections in a community.

The therapeutic effect of intranasally administered enviroxime was tested against naturally occurring common colds. The double-blind evaluation was carried out in Tecumseh, Mich., during a period when rhinoviruses are usually the principal pathogen. Rhinovirus transmission followed the typical pattern during this period of study. Although there were trends indicating greater therapeutic effectiveness for enviroxime when certain nasal symptoms were considered, there were no consistent statistically significant differences between treated and untreated groups. Results were unchanged when illnesses in different periods or associated with rhinovirus isolation were examined. It was concluded that no therapeutic effect of enviroxime was demonstrated.

Adolescent↗

Sequence analysis of a PM2-DNA anti-Z-IgG-binding region.

An anti-Z-antibody-binding region between PM2-DNA map units 0.05 and 0.18, containing approx. 25% of the bound PM2 antibody molecules (1,2) has been sequenced. Analysis of this PM2 DNA sequence from map units 0.00 to 0.175 demonstrates that alternating purine/pyrimidine tracts capable of adopting the left-handed conformation are present within this antibody-binding region. Longer (GC)n-rich tracts are clustered together and comprise seven alternating purine/pyrimidine-rich areas (48%-84%) ranging from 19 to 142 nucleotides in length. The DNA located between these alternating purine/pyrimidine-rich areas exhibit a low level (0%-19%) of this sequence arrangement. There is a very strong correlation between the alternating purine/pyrimidine-rich areas and the anti-Z-DNA-IgG-binding sites. Nucleotides 1461-1583 of the PM2-DNA genome encode the bacteriophage capsid protein IV. One of the PM2 left-handed sites is located within this protein-coding sequence; a B-to-Z transition within this site may be involved in protein-IV gene regulation in vivo.

Bacteriophages↗

A descriptive study of neuritic plaques and neurofibrillary tangles in an autopsy population.

From July 1, 1980 to December 2, 1982, all individuals at autopsy at the University of Michigan Medical Center greater than or equal to 65 years of age and selected individuals less than 65 years of age were examined for neuritic plaques and neurofibrillary tangles. Sections of the hippocampal, parahippocampal temporal gyrus, and fusiform gyrus were examined. In a total population of 199, each individual was classified as having none, few, or many of each lesion. The frequency of the joint presence of many plaques and tangles increased monotonically after age 71 years. There was no significant difference in the joint distribution of these lesions with sex or race. There was a strong correlation between the presence of one lesion and the other; the correlation for the two lesions was similar for males and females, but for blacks, it was significantly higher than for non-blacks. The distribution of these lesions in autopsy populations may be useful in identifying other related hypothetical risk factors for dementia of Alzheimer's type.

Age Factors↗

Problems of water storage in the rural village home: the Egyptian zir.

Although the potential adverse health impact of domestic water storage vessels that are used frequently in developing countries has been widely recognized, a search for systemic investigations found little data. This report describes the use of water storage vessels in rural Egyptian homes. This system of storage was found to have a number of implications: (1) for quality and quantity of water used in the house, (2) for undermining the potentially positive health benefits of current and new water supply programmes and (3) for confounding the interpretation of epidemiological investigations on water-related disease transmission.

Egypt↗

Left-handed Z-DNA regions are present in negatively supercoiled bacteriophage PM2 DNA.

Bacteriophage PM2 DNA is a 10-kb covalently closed circular (ccc) molecule with a reported superhelical density of sigma = -0.12. Here we describe the binding of anti-Z-DNA antibodies to PM2 form I DNA under high and low salt conditions. The binding to PM2 DNA has been demonstrated by competitive radioimmunoassay (RIA), retardation of the DNA:antibody complexes in agarose gels and visualization by electron microscopy. The antibody binding is dependent on the degree of negative supercoiling. Thus, PM2 form II and form III did not bind the antibody. The low salt RIA results indicated the presence of 200-400 bp of left-handed DNA per PM2 molecule. This could reduce the effective superhelical density to sigma = -0.04 to -0.08, a range comparable with those found for other ccc DNAs in vivo. Electron microscopy revealed that a maximum of 22 antibody molecules bind to PM2. Single-site restriction with HpaII of the fixed DNA:antibody complex showed a cluster of four to five antibody molecules bound near one end of the linear DNA molecule. The evidence presented indicates that PM2 DNA contains regions of left-handed conformation under physiological conditions (low salt concentration) as well as at high salt concentrations. In addition, electrophoretic analyses of PM2 topoisomers indicate the presence of left-handed regions at superhelical densities less than that of isolated PM2 DNA.

Antigen-Antibody Complex↗

Natural occurrence of left-handed (Z) regions in PM2 DNA.

Bacteriophage PM2 DNA, a ccc genome of high apparent superhelical density, contains left-handed (Z) regions as detected by competitive radioimmunoassay, agarose gel electrophoresis of DNA: antibody complexes and immunoelectron microscopy. The latter technique, in conjunction with partial blockage of restriction endonuclease sites by bound antibody, was used to map the left-handed regions along the DNA molecule. A cluster of four to five antibody molecules (approximately 25% of bound antibody) was located within map units 0.05-0.18 of the single Hpa II restriction site. Sequence analysis of part of this region showed the presence of several areas of high alternating purine-pyrimidine content. A strong correlation is observed between alternating pyrimidine-purine tracts of significant length and antibody binding sites.

Antibodies, Viral↗

Evaluation of an attenuated, cold-recombinant influenza B virus vaccine.

A live, attenuated influenza B virus vaccine was evaluated in a group of students. The virus, cold-recombinant (CR) 7, was produced by recombining the attenuated cold-adapted parent, B/Ann Arbor/1/66, with a wild strain, B/Hong Kong/8/73. In ferrets, the wild strain produced histopathologic lesions in the lungs, whereas the CR strain and the attenuated parent did not. A total of 306 individuals was inoculated intranasally with either the CR virus or a placebo. After inoculation, only one symptom was significantly more common in the vaccinees than in the control subjects. That symptom, sore throat, occurred briefly in 26% of the vaccine recipients and in 10.5% of the placebo recipients. An outbreak of influenza B occurred three months after vaccination. When serologic infection rates in the two groups were compared, it was found that the vaccine had been significantly effective (P less than 0.01) in preventing infection.

Animals↗

Prevalence and intensity of Schistosoma haematobium infection in six villages of upper Egypt.

A cross-sectional survey for Schistosoma haematobium infection in 5,998 individuals, representing 31,803 persons in six rural villages of the Qena governorate, Upper Egypt, was completed. There were 2,223 persons (37.1%) excreting S. haematobium eggs identified by the nuclepore membrane filtration technique of a single urine specimen. Prevalence of infection ranged from 23.9% to 64.0% among the six villages. Quantitatively the overall geometric mean egg-count was 48.1 eggs/10 ml urine. A survey of proximal canals was conducted and 9 of 4,312 Bulinus snails were infected with schistosomes (0.21%). The stools of 2 of 507 adolescent males were positive for S. mansoni. No Biomphalaria snails were found. When these findings are compared to past studies, S haematobium prevalence appears to have substantially increased.

Adolescent↗

An epidemiological investigation of health risks related to solid waste salvage and recycling in an Egyptian community.

This is the first report of an epidemiological cross-sectional study of solid waste scavengers, called Zabaline, in Egypt. The Zabaline communities provide an important solid waste collection service throughout Egypt's urban sector. Their economic viability depends entirely on salvaging solid waste for recycling. Intestinal parasites were common among the Zabaline examined; 48% were found with one or more protozoan or helminth infections. Either Schistosoma haematobium or S. mansoni or both infections were found in 19% of the sample although there was an apparent lack of a local transmission focus. Ascaris lumbricoides was the most frequently seen parasite (26.0%) and Entamoeba histolytica was seen infrequently (1.6%). Physical hazards of sorting solid waste was assessed and general illness occurring during the previous month recorded. Estimates of infant mortality showed elevated measures (IMR = 205/1000). The results indicate a need for the improvement of environmental conditions and health care in the Zabaline community and suggest that other similar scavenger groups may be at risk as well.

Adolescent↗

Interaction of DEAP fluoranthene (RMI 9563 DA) with DNA and metaphase chromosomes.

A fluorescent compound, DEAP fluoranthene (a tilorone cogener), has been suggested to bind to DNA by intercalation. The interaction of this drug with natural and synthetic DNAs and human metaphase chromosomes has been investigated in detail. DEAP fluoranthene shows a slight A-T preference in binding to DNA and was also found to change the topological winding number of superhelical DNA. These data, and the determined unwinding angle of 27 degree for DEAP fluoranthene, strongly support an intercalation mode of binding for this drug to DNA. DEAP fluorescence is minimally quenched when intercalated between A-T base pairs and maximally quenched when interacting with G-C base pairs. DEAP fluoranthene was found to produce bright fluorescent bands on human metaphase chromosomes identical to those produced by quinacrine. The solution data on DEAP fluoranthene interaction with DNA can be used to rationalize the production of differential banding patterns on chromosomes by DEAP fluoranthene in which the drug reports underlying DNA sequence arrangement of the metaphase chromosome.

Chromosome Banding↗

An anlysis of three parameters of covert positive reinforcement.

Investigated the active components of covert positive reinforcement (CPR) with a 2 X 2 X 2 factorial design (N = 64) that consisted of an S-R modality (covert vs. overt), a reinforcement procedure (covert vs overt), and a demand for expectancy of success (high vs. low). Posttreatment and follow-up results of the Behavioral Avoidance Test indicated that generally Ss in the overt S-R modality groups approached closer to the rat than did those in the covert groups (N = 64). More importantly, the S-R modality X demand interactions reflected that those Ss in the two covert S-R modality groups under low demand evidenced less approach than those Ss in the other six groups (p less than .01). Self-rating measures of anxiety on the Self-Rating Rat Anxiety Scale and the Fear Intensity Scale reflected overall decrements of fear from pretreatment to posttreatment and follow-up. Follow-up analyses indicated that plans should be made for the generalization of treatment effects by varying the treatment setting and perhaps by employing multiple therapists.

Animals↗