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Biomedical subjects

R C Page

Publications and source records attributed to R C Page.

At least 55 records · Page 3Linked to original sources
PubMed1996

Explaining variable absorption of a hypolipidemic agent (CGP 43371) in healthy subjects by gamma scintigraphy and pharmacokinetics.

The gastrointestinal absorption of a hypolipidemic agent (CGP 43371) was investigated using an external scintigraphy technique in six healthy men. After an overnight fast, subjects received a single 800-mg oral dose of CGP 43371 (4 capsules of 200 mg each) and one capsule of radioactive samarium-153 oxide (100-130 microCi) as a nonabsorbable marker of gastrointestinal transit and fecal recovery for CGP 43371. In vivo gastrointestinal transit of samarium-153 was monitored via gamma scintigraphy for 48 hours after administration to coincide with blood sampling. Samarium-153 content in whole fecal samples was determined by external gamma scintigraphy, and CGP 43371 content in both fecal and plasma samples was determined using high-performance liquid chromatography (HPLC). The results of fecal analysis indicated that transit of the two compounds in the gastrointestinal tract were similar, and bioavailability of CGP 43371 was calculated to be 9% based on the difference between the cumulative amounts of the nonabsorbable radioactive marker and CGP 43371 found in the feces. The onset of drug absorption occurred 4 hours after administration when radioactive samarium-153 was in the distal small bowel, and peak plasma drug level occurred 6 hours after administration, which corresponded with the arrival of samarium-153 in the terminal ileum and ileal/cecal junction. This observation supported the concept that primary absorption of this compound was in the distal to terminal portion of the ileum. Although the onset of drug absorption was delayed, it was curious that the rate of gastric emptying also affected the extent of absorption. A positive correlation (r = 0.91) between area under the drug curve (AUC) and area under the transit curve (AUTC) of the gastric emptying showed that longer gastric residence improved oral absorption of CGP 43371.

Adult↗
PubMed1996

Shared antigens of Porphyromonas gingivalis and Bacteroides forsythus.

Periodontitis in humans is caused by a group of predominantly gram-negative, anaerobic bacteria among which Porphyromonas gingivalis and Bacteroides forsythus are prominent. A similar group is present and presumably plays a similar role in experimental periodontitis in the primate Macaca fascicularis. Nevertheless, immunization using a vaccine containing only killed P. gingivalis suppresses the progress of experimental periodontitis in M. fascicularis. We investigated the hypothesis that gram-negative periodontopathic bacterial may share antigens, and immunization with one species may induce antibodies reactive with other gram-negative species. Using enzyme-linked immunosorbent assay (ELISA), Western and dot immunoblots with nonabsorbed and absorbed and immune and preimmune sera we show that monkeys immunized with P. gingivalis produce antibodies reactive not only with antigens of P. gingivalis but also with those of B. forsythus. Similarly, rabbits immunized with P. gingivalis or with B. forsythus produce antibodies that react with antigens of both bacteria. Cross-reactive antibodies bind to epitopes in lipid A and possibly in core carbohydrate of lipopolysaccharide. Using complexes of lipopolysaccharide with polymyxin B, bovine serum albumin and apolipoprotein A1 specificity of binding was documented. Using sera from monkeys immunized with P. gingivalis, cross-reactivity with Actinobacillus actinomycetemcomitans could not be demonstrated by ELI-SA, although binding to lipopolysaccharide but not to lipid A was demonstrated by Western and dot immunoblots. Antibodies to shared lipopolysaccharide epitopes of periodontopathic bacteria may account, at least in part, for the immune protection observed in immunized monkeys, and shared epitopes may have potential as a vaccine for periodontitis in humans.

Animals↗
PubMed1996

A multi-center clinical trial of a new chairside test in distinguishing between diseased and healthy periodontal sites. II. Association between site type and test outcome before and after therapy.

The aim of the present study was to evaluate the association between the outcome of a chairside test measuring gingival crevicular fluid (GCF) levels of the enzyme aspartate aminotransferase (AST) and other clinical measures of disease including probing depth, severity of inflammation, and GCF flow before and after therapy. We studied 91 patients with moderate to severe periodontitis. Eight sites with probing depths between 5 mm and 8 mm and obvious signs of inflammation were selected and designated diseased sites. Four sites with probing depth < or = 3 mm with no or minimal signs of inflammation were selected and designated non-diseased sites in patients. Thirty healthy individuals were enrolled and four sites in each were selected and designated healthy controls. Patients were treated with scaling and root planing and control subjects with supragingival prophylaxis. Measurements including GCF volume, gingival inflammation, and probing depth were performed at screening baseline, 1 week later at pretreatment baseline, and at weeks 2 and 4 after treatment. AST content of GCF was measured using a chairside colorometric test. It was concluded that the outcome of the test is an effective objective measure distinguishing between diseased sites and non-diseased sites in patients and control subjects when evaluated both prior to and following application of therapy. Use of this simple chairside test, when combined with other standard diagnostic procedures, provides an objective measurement permitting improved capacity to distinguish between diseased and non-diseased periodontal sites, and to better assess and monitor the outcome of therapy.

Adult↗
PubMed1995

Immunodominant antigens of Porphyromonas gingivalis in patients with rapidly progressive periodontitis.

W studied 4 isolates of Porphyromonas gingivalis, ATCC 33277, 381, A7A1-28, and W50, to identify major cell surface antigens and select the best strain from which to obtain antigen for a test vaccine. Immunoglobulin G (IgG) titers measured by enzyme-linked immunosorbent assay using whole-cell sonicates as antigen were significantly elevated for the sera of 64 rapidly progressive periodontitis patients relative to sera of 30 normal control subjects for each of the 4 strains studied. Western blots were prepared for all 4 strains and developed using sera from 22 patients and 20 control subjects to identify and determine the frequency of antibody-binding components. The intensity of binding by patient sera was greatest for the 75-kDa and 55-kDa components. The 43-kDa component was also widely recognized. Strains ATCC 33277 and 381 appeared to be antigenically similar. Because of the higher serum antibody titers, the larger proportion of seropositive patients and higher frequency of binding to specific protein components in Western blots, our efforts were focussed on strain ATCC 33277. Whole-cell sonicates, proteinase K-digested sonicate, lipopolysaccharide, capsular polysaccharide, and whole-cell protein fractions were prepared and evaluated for antigenic activity. By dot immunoblot, most of the antibody binding activity was found in the whole-cell protein fraction, with much lesser amounts in lipopolysaccharide and none in capsular polysaccharide. The antibody-binding activity was accessible on the cell surface, since 98.9% of P. gingivalis-specific antibody, including antibody binding to the 43-kDa, 55-kDa components on Western blot, was removed by whole-cell adsorption. Furthermore, the 43-kDa and 55-kDa but not the 75-kDa component on intact cells were accessible for labeling with 125I, confirming their cell surface location and accessibility.

Adult↗
PubMed1995

Clinical characteristics of subjects with a missense mutation in glucokinase.

The clinical characteristics of subjects with a missense glucokinase mutation, gly299-->arg, were studied in a large pedigree, BX, initially characterized by some members having Maturity Onset Diabetes of the Young (MODY). Glucose tolerance, beta cell function and insulin sensitivity were measured with Homeostasis Model Assessment (HOMA) and with a 'Continuous Infusion of Glucose with Model Assessment' (CIGMA) test. Diabetic complications were clinically assessed. Subjects with glucokinase gly299-->arg were the same age, height, and obesity as the subjects without the mutation. Diabetes was usually asymptomatic at diagnosis and was treated with diet alone in 15 of the 18 subjects. Five of the 11 adult females had been diagnosed when they developed gestational diabetes. The fasting plasma glucose concentrations at the time of study were 4.3-12.6 mmol l-1, with the higher levels being in the more obese (p < 0.05) and in the older subjects (p < 0.05). In subjects with the mutation, beta cell function was impaired, being geometric mean 63% (normal-100%) compared with 126% in the subjects without the mutation (p < 0.001) measured by HOMA and in a subset assessed by CIGMA 59% and 127% (p < 0.01), respectively. There was no difference in fasting insulin concentrations, insulin sensitivity, lipid concentrations or blood pressure between the groups. The haemoglobin A1c was raised (mean 6.5% compared with 5.5% in the subjects without the mutation), but microvascular and macrovascular complications were uncommon. The subjects with the mutation did not have microalbuminuria but had an impaired vibration perception threshold compared with subjects without the mutation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

A multicenter clinical trial of PerioGard in distinguishing between diseased and healthy periodontal sites. (I). Study design, methodology and therapeutic outcome.

We designed and performed a multicenter clinical trial to determine the relationship between measurements of the level of the enzyme aspartate aminotransferase (AST) in gingival crevicular fluid (GCF) to other measures used to detect periodontal disease and monitor outcome of treatment, including pocket depth and gingival inflammation. 32 periodontitis patients were enrolled at the University of Washington, Seattle, 30 at the University of Florida, Gainesville, and 34 at the University of Illinois, Chicago. 10 periodontally normal control subjects were enrolled at each location. 8 diseased and 4 healthy sites were designated for study in each patient and 8 healthy sites designated in each control subject. Measures of disease included pocket depth, severity of gingival inflammation, and GCF volume. AST levels were measured using the PerioGard test kit. Clinical measurements were made and GCF samples harvested and tested 2x before and 2x after therapy consisting of scaling and root planing under local anesthetic. Specific design and other issues are discussed, including selection of patients and control subjects, sample size, selection of experimental test sites, methods for assessment of diseased and therapeutic improvement, harvesting of GCF and selection of appropriate biostatistical methods for data analysis. Demographics of the patient populations at the 3 locations are reported. As expected, therapy induced only negligible changes in the measures of disease at healthy sites in control subjects, and relatively minor improvement in healthy sites in patients. In contrast, statistically significant improvement relative to pretreatment baseline status in all 3 measures of disease was observed for diseased sites at all 3 study locations with all p-values less than 0.0002. The magnitude of improvement was comparable to that reported previously by others. The % of PerioGard-positive sites decreased significantly between the screening baseline and both post-treatment visits for patients at all 3 locations, with p values of 0.0001 to <0.0008.

Adult↗
PubMed1995

Ability of bacteria associated with chronic inflammatory disease to stimulate E-selectin expression and promote neutrophil adhesion.

Porphyromonas gingivalis, Pseudomonas aeruginosa, and Helicobacter pylori have been shown to be associated with adult periodontal disease, chronic lung infections, and peptic ulcers, respectively. The ability of these bacteria to stimulate E-selectin expression and promote neutrophil adhesion, two components necessary for the recruitment of leukocytes in response to infection, was investigated. Little or no stimulation of E-selectin expression was observed with either P. gingivalis or H. pylori when whole cells, lipopolysaccharide (LPS), or cell wall preparations added to human umbilical cord vein endothelial cells were examined. P. aeruginosa was able to induce E-selectin to near-maximal levels; however, it required approximately 100 to 1,000 times more whole cells or LPS than that required by E. coli. Neutrophil-binding assays revealed that LPS and cell wall preparations obtained from these bacteria did not promote endothelial cell adhesiveness by E-selectin-independent mechanisms. In addition, P. gingivalis LPS blocked E-selectin expression by LPS obtained from other bacteria. We propose that lack of E-selectin stimulation and the inability to promote endothelial cell adhesiveness are two additional indications of low biologically reactive LPS. We suggest that this property of LPS may contribute to host tissue colonization. In addition, the ability of P. gingivalis to inhibit E-selectin expression may represent a new virulence factor for this organism.

Bacterial Infections↗
PubMed1995

Critical issues in periodontal research.

The purpose of this paper is to highlight briefly the major achievements and the remaining critical issues in the areas of epidemiology, microbiology, pathogenesis, diagnosis, and therapy. Periodontitis affects a relatively small proportion of study populations in the United States and other countries. Prevalence may be decreasing, but that remains to be seen. The identity and characteristics of susceptible individuals and groups are not known, and risk indicators for severe disease are only beginning to be identified. A very large number of different microbial species has been implicated in the etiology. It seems unlikely that all of these are essential participants. Essential participants need to be identified and better characterized. Whether putative pathogens are members of the commensal flora or exogenous species that must be transmitted is unclear. The relationship between the presence of a pathogenic flora and disease status is obscure. Pathogenic bacterial species are essential, but insufficient to cause disease. A susceptible host and local environmental factors--for example, elevated iron concentration--may be necessary for disease to occur. Many clonal types may not be virulent, and numbers greater than certain threshold levels appear to be necessary. The pathways by which bone and connective tissues of the periodontium are destroyed are sufficiently understood to permit development of therapies aimed at their modification. Examples are the use of vaccines, topical application of anti-inflammatory drugs, and use of chemically modified tetracyclines.

Aggregatibacter actinomycetemcomitans↗
PubMed1994

Segregation analysis of NIDDM in Caucasian families.

Non-insulin-dependent diabetes mellitus (NIDDM) has a substantial genetic component, but the mode of inheritance and the molecular basis are unknown. We have undertaken segregation analysis of NIDDM after studying 247 subjects in 59 Caucasian nuclear pedigrees ascertained without regard to family history of the disorder. The analyses were performed using POINTER and COMDS, which are computer programs which apply statistical models to the data. POINTER analysis was performed defining the phenotype as a presence or absence of hyperglycaemia. Among single locus hypothesis, the analyses rejected a recessive model and favoured a dominant model, but could not statistically show that this fitted better than a mixed model (a single locus against a polygenic background) or a polygenic model. COMDS analysis assumed a continuum of hyperglycaemia from normality to NIDDM, classified family members into a series of diathesis classes with increasing plasma glucose levels and compared the distribution with that found by screening the normal population. This analysis improved the likelihood of a dominant single locus model and suggested a gene frequency of 7.4%. It raised the possibility of a second locus, but cannot identify or exclude a polygenic model. In conclusion, two types of segregation analyses rejected a recessive model and favoured a dominant model of inheritance, although they could not statistically show that this fitted better than the polygenic model. The results raised the possibility of a common dominant gene with incomplete penetrance, but genetic analysis of NIDDM needs to take into account the likelihood of polygenic inheritance with genetic heterogeneity.

Adult↗
PubMed1994

Macaca fascicularis as a model in which to assess the safety and efficacy of a vaccine for periodontitis.

We have assessed Macaca fascicularis as a potential model in which to test the efficacy and safety of a vaccine for periodontitis. Twenty-eight animals were surveyed and 20 studied in more detail. Clinical periodontal status was assessed, the subgingival microflora analyzed especially for the presence and proportions of Porphyromonas gingivalis and titers and avidities of serum antibodies reactive with P. gingivalis measured. Probing depths ranged from 0.90 mm to 3.80 mm, Gingival Index scores from 0.00 to 4.00 and Plaque Index scores from 0.00 to 3.00. About 40% of sites bled on probing. The animals manifested a subgingival flora characteristic of the anaerobic gram-negative bacteria found in human periodontal pockets, including Actinobacillus actinomycetemcomitans, P. gingivalis, Bacteroides forsythus, Campylobacter rectus, Prevotella intermedia and Fusobacterium nucleatum. P. gingivalis was detected in 70 of 80 samples studied, ranging from 0.01% to 20% of the total flora. Serum antibody reactive with antigens of P. gingivalis was observed in all animals, with titers ranging from 1.0 enzyme-linked immunosorbent assay (ELISA) unit to 25 ELISA units and avidities from 0.10 M to 2.20 M. Antibody titer and maximum percentage of P. gingivalis were inversely correlated, indicating that a humoral immune response may be effective in reducing P. gingivalis overgrowth. M. fascicularis appears to be an excellent model for use in vaccine development.

Animals↗
PubMed1994

Obesity associated insulin resistance occurs in hypopituitary subjects.

The study aimed to assess the role of pituitary hormones in the relationship between insulin resistance and obesity. Twelve male subjects with hypopituitarism secondary to surgery for a non-functioning pituitary adenoma were recruited. Subjects were receiving replacement hormones. Fasting plasma samples were taken for insulin, C-peptide, glucose, and lipids. Body mass index and blood pressure were measured. In hypopituitary subjects on replacement therapy, a positive association between body mass index and fasting plasma insulin levels (r = 0.76, p < 0.004) was similar to that found in normal subjects. In conclusion pituitary function does not have a direct role in determining the relationship between fasting plasma insulin, an index of insulin resistance, and obesity.

Humans↗
PubMed1994

Effect of treatment on titer, function, and antigen recognition of serum antibodies to Actinobacillus actinomycetemcomitans in patients with rapidly progressive periodontitis.

Although periodontal treatment by scaling and root planing (SCRP) is known to induce bacteremia, the effect of this procedure on the host immune response is not known. We have determined pre- and post-SCRP immunoglobulin G antibody titers to antigens of Actinobacillus actinomycetemcomitans in the sera of 22 patients with rapidly progressive periodontitis. We also assessed the ability of these sera to enhance phagocytosis and killing of A. actinomycetemcomitans by human polymorphonuclear leukocytes by using a polymorphonuclear leukocyte chemiluminescence (CL) assay. Specific anti-A. actinomycetemcomitans antibody titers were significantly increased at 6 and 12 months after beginning treatment, and CL values were significantly increased at 12 months, whereas mean interproximal pocket depths were significantly decreased at 12 months after beginning treatment. When patients were classified as either seropositive (twice the median titer of control subjects; n = 10) or seronegative (n = 12), both median titers and CL values were significantly increased for the seronegative group at 6 and 12 months after treatment. In the seropositive group, only the median titer was significantly increased at 12 months. Western blot (immunoblot) patterns for six seronegative and six seropositive patients differed remarkably at the baseline. Before treatment, all of the seropositive patients recognized high-molecular-mass lipopolysaccharide (LPS) and a large number of protein components. Patterns were virtually unaffected by therapy. Before treatment, only one of the seronegative patients recognized the LPS smear and none reacted strongly with protein components. Following treatment, slight LPS staining was observed for five of six seronegative patients and detection of protein bands was enhanced in all cases. We conclude that treatment by SCRP induces a humoral immune response, especially in seronegative patients, and that response may play a role in the observed beneficial effects of periodontal treatment.

Adult↗
PubMed1994

Immunization against Porphyromonas gingivalis inhibits progression of experimental periodontitis in nonhuman primates.

Periodontitis is a common infectious disease in which the attachment tissues of the teeth and their alveolar bone housing are destroyed, resulting in tooth loss. The gram-negative anaerobic microorganism Porphyromonas gingivalis has been closely linked to severe forms of the disease. We show for the first time that immunization of the primate Macaca fascicularis with killed P. gingivalis in Syntex Adjuvant Formulation-M inhibits progression of periodontal tissue destruction.

Animals↗
PubMed1994

Direct detection of Porphyromonas gingivalis in Macaca fascicularis dental plaque samples using an oligonucleotide probe.

Oligonucleotide probes complementary to the hypervariable regions of the 16S rRNA of Porphyromonas gingivalis, and previously shown to specifically identify human P. gingivalis strains to the species level, were tested for their ability to recognize P. gingivalis from nonhuman primates (Macaca fascicularis), either as distinct isolates or in subgingival dental plaque. The 32P-labeled probes hybridized with all 147 monkey isolates identified as P. gingivalis by morphology and biochemistry, but did not hybridize with any of the 331 isolates representing 17 genera of bacteria unrelated to P. gingivalis, or to the more closely related P. endodontalis and P. asaccharolytica. This corresponds to sensitivities and specificities of 100%. Of 76 M. fascicularis plaque samples, P. gingivalis was detected by probe and culture in 67. Of 26 human plaque samples taken from separate individuals free of periodontal disease, 23 failed to demonstrate P. gingivalis by probe or culture. The results of the combined 102 monkey and human plaque samples indicate that, when compared to culture as the "gold standard," the P. gingivalis probe had a sensitivity of 96%, a specificity of 87%, and an overall agreement with culture of 93%. These results reveal that the oligonucleotide probes used to identify P. gingivalis are specific for this organism, and give results comparable to culture methods for detecting the presence of P. gingivalis in M. fascicularis dental plaque.

Animals↗
PubMed1994

The humoral response in patients with periodontitis: effects of treatment and prospects for a vaccine.

Research indicates that human periodontitis is caused by bacteria. Although the roles of host factors are not clear, these factors are important in the development of this disease. The immune response that occurs in patients with infectious diseases, and that eventually arrests the process of the infection, does not appear to happen in patients with periodontitis. This article presents the results of studies that attempted to determine if periodontitis patients mount a humoral response during the course of their infection, if the antibodies produced are protective, and, if not, why these reactions fail to occur or why they are ineffective in halting the disease.

Aggressive Periodontitis↗
PubMed1993

Interleukin-1 beta regulation of fibroblast proteoglycan synthesis involves a decrease in versican steady-state mRNA levels.

This study investigates the effects of interleukin (IL)-1 beta on proteoglycan metabolism by fibroblasts surrounded by endogenous extracellular matrix. In both three-dimensional matrix cultures and long-term monolayer cultures IL-1 beta caused a significant decrease in synthesis and deposition of sulphated proteoglycans, but had no effect on release of deposited material. The decrease in synthesis became successively more pronounced, and corresponded to 40-60% of the control after 72 h incubation. The reduction was almost totally accounted for by an effect on the chondroitin ABC-lyase-sensitive proteoglycans. Gel electrophoresis showed a significant decrease in a high-molecular-mass chondroitin ABC-lyase-sensitive proteoglycan after incubation with IL-1 beta. Northern-blot analyses of total RNA revealed a pronounced decrease in the steady-state mRNA levels of versican, the large chondroitin sulphate, with levels corresponding to 10-30% of controls. In comparison, the steady-state mRNA level for decorin, the major sulphated proteoglycan synthesized by the cells, was only slightly affected. The prominent decrease in synthesis of sulphated proteoglycans induced in long-term fibroblast cultures, including the pronounced decrease in versican steady-state mRNA levels, is likely to have a significant effect on the structure of the extracellular matrix. Induction of this type of change may constitute a significant mechanism whereby IL-1 beta can affect the properties of connective tissue during inflammation and wound healing.

Blotting, Northern↗