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Biomedical subjects

D Williams

Publications and source records attributed to D Williams.

At least 217 records · Page 12Linked to original sources
PubMed1997

Morphological and structural characteristics of the proximal femur in human and rat.

Because the ovariectomized rat model of postmenopausal osteoporosis is the most commonly used small animal model to investigate consequences of bone loss on bone structure and strength, or to assess benefits of the various therapeutic strategies to improve bone mass and strength, the attempt was made to compare histoanatomical and structural characteristics of the femoral neck between human and rat models. In addition to different biomechanics, there is a significant difference in gross- and microanatomy of the proximal femur between humans and rats. Percent of the cortical bone component is much higher in rats (72.5%) relative to humans (12.5%). Also, cortical bone at the femoral neck in rats is evenly distributed, whereas in humans there is a considerable difference in the amount of the cortical bone between the superior half of the femoral neck with cortical thickness being only 0.3 mm, and the inferior half of the neck having 6-mm-thick cortex. Humans have far more cancellous bone at the femoral neck (22.7% average) relative to rats (6.8%). In addition, cancellous bone at the femoral neck in humans is unevenly distributed between the bone center and its periphery. Human samples exhibited striking differences in the cancellous bone structure between weight-bearing and tensile trabecular groups exhibiting clear trabecular orientation consisting of plates and rods, and trabeculae around the neutral bone axis with little mechanical activity exhibiting rod-like trabeculae only. Although humans and rats have a periosteum covering the femoral neck, and each lacks the muscular attachment at intracapsular portions of the femoral neck, rats, in contrast to humans, have the ability to quickly adapt cortical thickness and increase inertia to meet mechanical needs via modeling-dependent periosteal apposition.

Aged↗
PubMed1997

Infections with Roseomonas gilardii and review of characteristics used for biochemical identification and molecular typing.

Roseomonas is a recently described genus of gram-negative coccobacilli formerly designated as "pink-coccoid" groups I through IV by the Centers for Disease Control and Prevention (Atlanta, Ga) because of the organism's characteristic pink colonies. Since 1991 we have isolated Roseomonas from eight patients; in seven from blood cultures and in one from a skin lesion. The seven blood isolates were from patients with clinically significant underlying diseases who had central venous catheters in place; the majority were associated with polymicrobial catheter infections. Additional characteristics of their infections are described. The eight isolates had originally been identified by us as Centers for Disease Control (CDC) pink-coccoid group III. These organisms were re-identified using the criteria of Rihs et al, and all isolates fit most closely with Roseomonas gilardii. Antibiotic profiles were fairly homogeneous showing susceptibility to many antibiotics, but uniform resistance to cefoxitin, ceftazidime, and piperacillin. Attempts to determine whether the isolates were the same strain by pulsed-field gel electrophoresis suggested that 3 of the isolates were similar. Random amplified polymorphic DNA analysis, however, demonstrated that each of the eight isolates was a unique strain.

Adult↗
PubMed1997

Paroxetine increases heart rate variability in panic disorder.

Panic patients have decreased heart rate variability, a risk factor for sudden cardiac death, and increased rates of cardiac death and stroke. Imipramine has been found to further reduce heart rate variability in panic. This study uses power spectral analysis to compare autonomic components of heart rate variability in 16 unmedicated control subjects and 17 panic patients before and after treatment with paroxetine at 20 mg/day for 4 weeks. Patients had higher predrug reclining and standing sympathetic activity than control subjects. After drug, patients' total sympathetic activity decreased. Predrug patients failed to increase sympathetic activity on orthostasis, lacking the normal baroreflex response found in control subjects. After drug, patients normalized this sympathetic component of the baroreflex response. Before drug, patients' parasympathetic reclining and standing activity did not differ from control subjects, and patients showed the normal orthostatic parasympathetic decrease. After drug, patients' total parasympathetic activity increased, whereas the baroreflex response was preserved. Nine medicated patients had more than a 50% reduction of panic attacks. In view of paroxetine's increase of heart rate variability, potential benefits of selective serotonin reuptake inhibitors in decreasing cardiac mortality in panic disorder are discussed.

Adult↗
PubMed1997

Limited diversity of Streptococcus pneumoniae psaA among pneumococcal vaccine serotypes.

The pneumococcal surface adhesin A (PsaA) is a surface-exposed protein of the gram-positive bacterium Streptococcus pneumoniae. It belongs to a group of proteins designated the lipoprotein receptor I antigen family. The gene encoding PsaA from an encapsulated strain of pneumococcal serotype 6B was cloned and sequenced. The peptide sequence was compared to that of homologs found in S. pneumoniae serotype 2, viridans streptococci, and Enterococcus faecalis. Identity values among the deduced peptides ranged from 57 to 98%. The polymorphism of psaA was examined among the 23 encapsulated vaccine serotypes by using PCR-restriction fragment length polymorphism analysis. Ten different enzymes were used to analyze 80 strains representing the 23 serotypes in a 23-valent polysaccharide vaccine. This analysis showed that restriction sites within the gene were highly conserved, with only a minor variation occurring in 10% of the strains, the result of an additional Tsp509I site. The lack of variation for the other restriction sites within the gene examined here indicates that psaA is genetically conserved, an important characteristic necessary for a candidate common protein vaccine.

Adhesins, Bacterial↗
PubMed1997

Ethanol, growth hormone and testosterone in peripubertal rats.

The deleterious effects of ethanol on the hypothalamic pituitary growth hormone axis in adult male humans and animals have been well documented. It is also well established that ethanol has toxic effects on testicular function in adult humans and animals. Much less is known, however, about the effects of ethanol on the growth hormone (GH) axis and testicular function in adolescence. Recent studies have established that adolescent problem drinking is a widespread and growing threat to the health of young people in the United States. In the present study, therefore, we investigated if acute ethanol exposure in peripubertal male Sprague-Dawley rats altered normal pituitary and testicular function. Serum levels of GH and testosterone were measured at 1.5, 3, 6, and 24 h after a single i.p. injection of either saline or 3 g/kg body weight ethanol. Histologic analysis as well as serum testosterone levels allowed us to assign animals to either early puberty (35-day-old animals), mid-puberty (41-day-old animals), or young adult (51- and 66-day-old animals) status. Ethanol produced significant decrements in serum testosterone in the 51- and 66-day-old animals, with a trend toward suppression in the 41-day-old group. Furthermore acute ethanol administration significantly decreased serum GH (P < 0.0001 by 3 way ANOVA) demonstrating a significant effect of ethanol on serum GH in all age groups and at all time points studied when compared with saline injected controls (P < 0.01 by Turkey's studentized range test). Despite this significant fall in peripheral GH levels, there was no decrease in either GH mRNA or growth hormone-releasing factor (GRF) mRNA levels nor in hypothalamic concentration of GRF peptide. We conclude that, as in adult animals, acute exposure to ethanol causes a prolonged and severe decrement in serum GH which is possibly mediated at the level of secretion. In addition, there is attenuation in testosterone secretion. These data are all the more important since GH and testosterone play critical roles in organ maturation during this stage of development.

Analysis of Variance↗
PubMed1997

Income dynamics and adult mortality in the United States, 1972 through 1989.

OBJECTIVES: The aim of this study was to examine relationships between income and mortality, focusing on the predictive utility of single-year and multiyear measures of income, the shape of the income gradient in mortality, trends in this gradient over time, the impact of income change on mortality, and the joint effects of income and age, race, and sex on mortality risk. METHODS: Data were taken from the Panel Study of Income Dynamics for the years 1968 through 1989. Fourteen 10-year panels were constructed in which predictors were measured over the first 5 years and vital status over the subsequent 5 years. The panels were pooled and logistic regression was used in the analysis. RESULTS: Income level was a strong predictor of mortality, especially for persons under the age of 65 years. Persistent low income was particularly consequential for mortality. Income instability was also important among middle-income individuals. Single-year and multiyear income measures had comparable predictive power. All effects persisted after adjustment for education and initial health status. CONCLUSIONS: The issues of low income and income instability should be addressed in population health policy.

Black or African American↗
PubMed1997

Mutagenesis: the power to do harm.

Among the portfolio of tests that may have to be performed on medical devices is the test for mutagenicity. It is far from clear, however, just how significant the risk is of mutagenicity from biomaterials, and how the results of these tests should be interpreted. This article discusses some of the salient features of this difficult subject.

Animals↗
PubMed1997

The engineering of polysaccharides.

Hyaluronan is a widely distributed and very important biological molecule of the polysaccharide family. Many of the functional characteristics of this substance can be retained when hyaluronan is transformed from a water-soluble substance into a structural biomaterial. This article highlights the potential applications of these materials in the regeneration of injured tissue.

Culture Techniques↗
PubMed1997

Ceramics transformed: manipulating crystal structures to toughen bioceramics.

Ceramics have tremendous potential as engineering materials for the construction of medical devices but are inhibited by their inherent brittleness. This article discusses how this problem has been addressed by the development of the process of transformation toughening and places this in the broader context of the new generation of "smart" materials.

Biocompatible Materials↗
PubMed1997

Size and shape really matter: the influence of design on biocompatibility.

Biocompatibility is normally equated with the characteristics of degradation and toxicity. However, there are many more ways by which a medical device can affect the host, including the way in which devices distribute stress in the tissues. This in turn implies that the design of the device can be influential in determining the host response.

Animals↗
PubMed1997

Engineering a concept: the creation of tissue engineering.

Tissue engineering is a fashionable phrase and a new concept. This article analyses what is meant by this term and discusses some of the products that may emerge from the translation of this concept into clinical reality.

Artificial Organs↗
PubMed1997

Disposition of amodiaquine and related antimalarial agents in human neutrophils: implications for drug design.

The development and clinical use of 4-aminoquinoline antimalarial agents such as amodiaquine have been limited by toxicity to neutrophils. We have investigated the chemical basis of amodiaquine-induced toxicity and compared the findings with those for established antimalarial drugs proposed for human use. Amodiaquine, like chloroquine, mefloquine and halofantrine, was lysosomotropic and accumulated in human neutrophils. Amodiaquine did not lead to impairment of either cellular function or cell viability at therapeutic levels. In contrast to other antimalarial agents, amodiaquine (because it contains a 4-aminophenol function) depleted glutathione in activated neutrophils, by formation of an electrophilic quinoneimine metabolite. Bioactivation was accompanied by the expression of a drug-related antigen on the cell surface, which was recognized by drug-specific antibodies, suggesting that a type II hypersensitivity reaction is responsible for the observed toxicity. Similar bioactivation and accumulation were observed for the structurally related amopyroquine. The effects of chemical modifications at the 3'- and 5'-positions, which are known to enhance antimalarial activity, were also investigated. The introduction of a lipophilic 5'-chlorophenyl group and 3'-t-butyl group blocked bioactivation but enhanced cellular accumulation, with resultant impairment of function and neutrophil viability, whereas introduction of a second cationic dialkylamino group (bis-mannich compounds) blocked bioactivation and reduced cellular accumulation, without producing noticeable effects on cellular function and viability. These data provide a chemical rationale for the idiosyncratic agranulocytosis observed with amodiaquine, and they suggest that similar toxicity might be anticipated for amopyroquine but is less likely with bis-mannich antimalarial agents such as pyronaridine.

Amodiaquine↗
PubMed1997

Cloning, sequencing, and embryonic expression of an N-ras proto-oncogene isolated from an enriched zebrafish (Danio rerio) cDNA library.

An enriched zebrafish (Danio rerio) complementary DNA library was constructed for screening of ras-related genes, and a positive clone was isolated from one plate of 3 x 10(4) plaques. This clone, Zras-B1, carried an insert of 2592 base pairs (bp) with an open reading frame encoding a ras p21 protein of 188 amino acids. The deduced amino-terminal 86 amino acid residues and the carboxy-terminal CAAX binding motif are identical to mammalian ras. The full-length Zras-B1-encoded protein is most closely related to human N-ras (91% identity), with lesser homology to Ha-ras (84%) and Ki-ras (85%). Preliminary screening data also indicate other ras genes in zebrafish, at least one of which is also transcribed in adults. A Zras-B1-related 3.1-kb transcript was found to be abundant in embryos from zygote through gastrulation, and may be maternally derived.

Amino Acid Sequence↗