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Biomedical subjects

R C Page

Publications and source records attributed to R C Page.

At least 73 records · Page 4Linked to original sources
PubMed1993

Association of low birth weight with beta cell function in the adult first degree relatives of non-insulin dependent diabetic subjects.

OBJECTIVE: To examine the relation between birth weight and beta cell function in the first degree relatives of non-insulin dependent diabetic subjects. DESIGN: Cross sectional study of 101 adults of known birth weight from 47 families which had at least one member with non-insulin dependent diabetes. SUBJECTS: 101 white adults aged mean 43 (SD 7) years. SETTING: Oxfordshire, England. MAIN OUTCOME MEASURES: Glucose tolerance was measured by continuous infusion glucose tolerance test. beta cell function and insulin sensitivity were calculated from the fasting plasma glucose and insulin concentrations with homeostasis model assessment. beta cell function was standardised to allow for the confounding effects of age and obesity. RESULTS: Twenty seven subjects had non-insulin dependent diabetes, 32 had impaired glucose tolerance, and 42 were normoglycaemic. Birth weight correlated with the beta cell function of the complete cohort (rs = 0.29, p = 0.005), the non-insulin dependent diabetic subjects (rs = 0.50, p = 0.023), and the non-diabetic subjects (rs = 0.29, p = 0.013). The non-insulin dependent diabetic (n = 27) and the non-diabetic (n = 74) subjects had similar mean (inter-quartile range) centile birth weight 50% (19%-91%), and 53% (30%-75%) respectively. Non-insulin dependent diabetic subjects had significantly lower beta function than the non-diabetic subjects: 69% (48%-83%) v 97% (86%-120%), p < 0.001. CONCLUSIONS: The cause of the association between low birth weight and reduced beta cell function in adult life is uncertain. Impaired beta cell function in non-insulin dependent diabetic subjects was not accounted for by low birth weight, and genetic or environmental factors are likely to be necessary for development of diabetes.

Adult↗
PubMed1993

Expression and function of gingival fibroblast C1q receptors are upregulated by interleukin-1 beta and transforming growth factor-beta.

In injury and inflammation, complement (C) component C1q, in addition to its central role in initiation of classical pathway of complement activation, modulates diverse cellular functions by binding to specific cell surface receptors. Interaction of substrate-bound C1q with receptors for the collagen-like domain of C1q (C1qRC) of human gingival fibroblasts (HGF) promotes cell attachment. We investigated modulation of the adhesive function and expression of C1qRC by interleukin-1 beta (IL-1 beta) and transforming growth factor-beta (TGF-beta). Confluent fibroblast monolayers were incubated under standard culture conditions with or without cytokines. C1qRC function was measured by attachment assays. IL-1 beta and TGF-beta increased fibroblast adhesion to C1q to 146% and 131% of controls, respectively. Cytokine enhancement of HGF adhesion was concentration-dependent, saturable (20 ng/ml IL-1 beta; 1 ng/ml TGF-beta) and time-dependent (IL-1 beta 12-hr peak; TGF-beta 24-hr peak). Effect of IL-1 beta and TGF-beta on C1qRC expression was assessed by flow cytometry measurements of fluorescence intensity of cells stained with C1q and FITC anti-C1q antibody, and by binding studies with 125I-C1q. Cells treated with cytokines displayed a two- to four-fold increased fluorescence of cell-bound C1q compared to controls. Binding studies indicated the increased fluorescence correlated with increase in number of C1qRC in both IL-1 beta (4.7 x 10(6)/cell) and TGF-beta (3.9 x 10(6)/cell)-treated cells, compared to control (3.0 x 10(6)/cell), but had no effect on binding affinity. Rates of internalization of receptor-bound C1q were similar in cytokine-treated cells and controls. We propose from these data that IL-1 beta and TGF-beta have the ability to upregulate C1qRC expression, and this effect contributes to increased adhesion of HGF to substrate-bound C1q.

Carrier Proteins↗
PubMed1993

Titer and subclass distribution of serum IgG antibody reactive with Actinobacillus actinomycetemcomitans in localized juvenile periodontitis.

Most patients with localized juvenile periodontitis (LJP) manifest serum IgG antibodies specifically reactive with antigens of Actinobacillus actinomycetemcomitans serotype b (Aa-b). Whether these antibodies are protective, destructive, or irrelevant to the progress of the disease remains unclear. We report results of studies aimed at assessing the subclass IgG responses in 35 LJP patients and 35 periodontally normal control subjects using well-characterized monoclonal antibody subclass reagents in an enzyme-linked immunosorbent assay. Our data show that the mean value for total IgG reactive with antigens of Aa-b was more than sevenfold higher for patients than for normal control sera (2349.6 micrograms/ml for patients vs 332.2 micrograms/ml for controls). Individual patients and control subjects were classified as high- or low-titer, using twice the median value for total anti-Aa-b IgG in control sera as the cutoff. Of 35 patients, 26 (74%) were high-titer, and 9 (26%) were low-titer. This compares to 5 normal control subjects (14%) high-titer and 30 (86%) low-titer. IgG2 accounted for the major quantitative response in both patients and control subjects. Indeed, the mean IgG2 values for both concentration and percentage of total specific IgG were greater than the combined values for specific anti-Aa-b IgG1, IgG3, and IgG4. Of the 26 high-titer sera, IgG2 predominated in 24, with IgG1 and IgG3 predominating in 1 each; IgG2 predominated in only 2 of the low-titer sera.

Actinobacillus Infections↗
PubMed1993

Prevalence and pathophysiology of impaired glucose tolerance in three different high-risk white groups.

Insulin resistance and beta-cell function were assessed by a continuous infusion of glucose in the following three groups of white subjects at risk of developing impaired glucose tolerance and diabetes: 41 subjects who were the offspring of patients with type II diabetes, 26 general-population subjects with an increased fasting plasma glucose level of at least 5.6 mmol/L on screening, and 22 subjects who had had gestational diabetes but were now nondiabetic. Subjects had a mean (+/- 1 SD) age of 43 +/- 9 years and a body mass index (BMI) of 27 +/- 5 kg/m2. Subjects with previously increased fasting glucose levels were significantly more insulin resistant than a control group, taking into account BMI, age, and gender (% normal insulin sensitivity [%], 59 [50 to 79] v 87 [73 to 96]; P < .005), and previously gestationally diabetic subjects showed greater impairment of beta-cell function (% normal beta-cell function [% beta], 69 [60 to 87] v 97 [89 to 105]; P < .005). Diabetes (defined by World Health Organization criteria) or impaired glucose tolerance (defined as an achieved plasma glucose concentration [APG] > 95th percentile of an age- and weight-matched population) was identified in 22% of family members, 31% of fasting hyperglycemic subjects, and 41% of previously gestationally diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Hyperglycaemic progression in subjects with impaired glucose tolerance: association with decline in beta cell function.

Impaired glucose tolerance is associated with an increased risk of Type 2 diabetes. This prospective cohort study has examined the variables associated with hyperglycaemic progression in order to elucidate the aetiology of this deterioration. The 5 mg glucose.kg ideal body weight.min-1 continuous infusion of glucose with model assessment (CIGMA) test was used to quantitate glucose tolerance, beta cell function, and insulin sensitivity. Twenty-two Caucasian subjects who had impaired glucose tolerance identified on two separate tests underwent repeat testing after a median period of 24 months. At follow-up, 2 of the 22 subjects (9%) had Type 2 diabetes, 18 (82%) had impaired glucose tolerance, and 2 (9%) were normoglycaemic. The fasting and achieved (60-min) glucose levels were significantly higher at follow-up (mean +/- SD) (5.7 +/- 0.8 vs 5.5 +/- 0.5 mmol l-1, p = 0.029 and 10.0 +/- 0.9 vs 9.6 +/- 0.6 mmol l-1, p = 0.021, respectively), and beta cell function was significantly lower (median and interquartile range): 75% (50-93%) vs 90% (70-135%), p = 0.009. The changes in fasting plasma glucose were found to correlate with change in body mass index (rs = 0.46, p = 0.03). We conclude that impaired glucose tolerance is associated with decline in beta cell function, and denotes substantial risk of hyperglycaemic progression. Randomized controlled trials are warranted to determine whether exercise programmes, dietary advice, and attentive follow-up and effective preventive strategies for subjects with impaired glucose tolerance.

Adult↗
PubMed1993

Macaca nemestrina: a non-human primate model for studies of periodontal disease.

The non-human primate Macaca nemestrina was evaluated for use as a potential model in periodontal research by study of 16 animals. Using one incisor, premolar, and molar per quadrant, we measured supragingival plaque, severity of gingival inflammation, and pocket depth, and analyzed the subgingival flora. Serum IgG titers and avidities to antigens of Porphyromonas gingivalis (Pg) and Actinobacillus actinomycetemcomitans (Aa) were also assessed. Ten animals were between 13 and 24 years old, and six were between 4 and 5 years old. While mean gingival inflammation scores were significantly higher for older than for younger animals (2.2 vs 1.8, p < 0.05), mean plaque index scores and mean probing depths did not differ significantly. The animals harbored a subgingival microflora considered to be pathogenic for humans including Aa, Pg, Bacteroides forsythus, Prevotella intermedia I and II, Campylobacter recta and Fusobacterium nucleatum. Aa, however, was found only in the younger animals. All of the animals had serum IgG antibodies reactive with antigens of Pg and Aa, and titers for Pg but not for Aa were significantly higher in the older relative to the younger animals (t test p < 0.02). In contrast, antibody avidity did not significantly differ between the two groups. A combined clinical assessment index based on maximum probing depth, gingival index score, and tooth loss was used to assess the overall disease severity. Titers were positively associated with disease severity (Spearman's rank correlation 0.57, p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1993

Effects of treatment on antibody titer to Porphyromonas gingivalis in gingival crevicular fluid of patients with rapidly progressive periodontitis.

Twenty-eight patients diagnosed as having rapidly progressive periodontitis (RPP) were enrolled in a study in which samples of subgingival microflora were harvested from test teeth and assayed for the presence of Porphyromonas gingivalis, and GCF collected and analyzed by ELISA for specific antibody for P. gingivalis. Clinical conditions were measured and recorded, and treatment by scaling and root planing provided at baseline and at 3, 6, 9, and 12 months. Reduction in pocket depth, stabilization of attachment level, and resolution of inflammation were comparable to previously reported values. By 3 months, mean and median specific antibody concentration had decreased, and continued to decrease through 12 months. The proportion of samples in which specific antibody was not detectable increased from 27% at baseline to 73% at month 12. GCF samples from sites at which P. gingivalis was present had greater than 2-fold higher median specific antibody than samples from P. gingivalis-negative sites. At baseline, specific antibody titer of 30-second GCF samples positively correlated with pocket depth, and GCF volume significantly correlated with antibody titer and concentration, and with pocket depth. In addition, change in specific antibody titer of 30-second samples from baseline to both 6 and 12 months correlated positively with pocket depths. Thus sites infected by P. gingivalis manifested high levels of specific antibody, and levels were related to clinical status. Following treatment, antibody levels decreased significantly as pocket depths decreased, attachment levels stabilized, and inflammation resolved.

Adult↗
PubMed1993

Periodontal therapy: prospects for the future.

Prior to the 1950s, periodontitis was treated mostly by tooth exfoliation or extraction, and that is still the predominant treatment for most of the world's populations today. Debridement of the root surface by scaling and root planning came into relatively common use in the first half of the present century and has become the central feature held in common by all currently-used forms of periodontal therapy. Until the 1980s, the most commonly-used treatment consisted of scaling and root planing, followed by resective surgery aimed at achieving zero pocket depth. During the 1980s, data were obtained demonstrating that the thoroughness of root debridement and subgingival infection control, not the presence or absence or periodontal pockets, is the major determinant of successful periodontal therapy, and non-surgical therapy became a commonly-used treatment. Neither resective surgery nor non-surgical therapy results in significant regeneration of periodontal attachment. With the realization that periodontitis is an infectious process, the use of antibiotics and other anti-infective agents came into common use as adjuncts to other standard therapies. An understanding of the pathways by which the soft and calcified tissues of the periodontium are destroyed has led to the likelihood of widespread future use of the non-steroidal, anti-inflammatory family of drugs to suppress alveolar bone destruction by blocking prostaglandin production, and to the use of chemically-modified tetracyclines that chelate divalent cations and thereby block tissue destruction by the metalloproteinases. Recent data clearly show that regeneration of the previously-destroyed periodontal attachment tissues is biologically possible, and regeneration has become the goal of therapy for the 1990s. Use of osteoconductive and osteoinductive graft materials can, under favorable conditions, induce roughly 60% to 70% regeneration of bone lesion height or volume with concomitant improvement in the clinical conditions. Regeneration by grafting may be further enhanced by use of barrier membranes that exclude gingival fibroblasts and epithelium from the healing site. Still further enhancement seems to be possible by local application of various growth factors, although studies in this important area are now only in their infancy. The future of periodontal therapy is exceedingly bright.(ABSTRACT TRUNCATED AT 400 WORDS)

Forecasting↗
PubMed1993

Availability of type II diabetic families for detection of diabetes susceptibility genes.

Type II diabetes is a familial disorder, as evidenced by the increased prevalence in monozygotic cotwins and first-degree relatives of affected subjects; however, its genetic etiology is largely unknown. Well-characterized pedigrees are an essential resource for the study of susceptibility genes for type II diabetes. This study describes a 5-yr search for type II diabetic families in Oxfordshire, U.K. We interviewed 950 type II diabetic subjects concerning the availability of first-degree relatives; 127 Caucasian families ascertained through a proband with type II diabetes were studied, and 589 first-degree relatives were characterized. Three large pedigrees with maturity-onset diabetes of the young, and 8 multiplex multigenerational type II diabetic pedigrees were identified. We identified 12 sib-pairs in which both siblings had type II diabetes; however, only 7 sib-pairs had both parents alive, and 2 of these had both parents affected. If one also considers one sib having diabetes and one sib having glucose intolerance as being an affected sib-pair, we identified 30 sib-pairs of which 7 had both parents affected and probably had bilineal inheritance. We identified 76 complete nuclear families with both parents and offspring available for study, but only 6 were of optimal structure for linkage analysis. In conclusion, multiplex pedigrees and type II diabetic sib-pairs with living parents are uncommon, and their ascertainment requires a substantial investment of resources. Large-scale collaborative multicenter initiatives would be needed to collect a large resource of family material for the study of susceptibility genes for type II diabetes.

Adult↗
PubMed1993

'Healthy living' and sulphonylurea therapy have different effects on glucose tolerance and risk factors for vascular disease in subjects with impaired glucose tolerance.

This study was undertaken to determine whether impaired glucose tolerance and associated risk factors for cardiovascular disease can be improved with 'healthy living' by diet and exercise or with sulphonylurea therapy. Patients were recruited by screening subjects with either a family history of type II diabetes, previous gestational diabetes, or a previously raised plasma glucose (5.6-6.6 mmol/l). Impaired glucose tolerance was defined as hyperglycaemia on two separate tests, an achieved glucose level after a glucose infusion test above the 90th percentile of an age-matched normal population (> 9.3 mmol/l) or a fasting plasma glucose above the 95th percentile (> 5.6 mmol/l). Thirty-seven subjects with impaired glucose tolerance were entered into a randomized, prospective study for 6 months with allocations to healthy living or double blind to sulphonylurea (gliclazide 40 mg twice daily) or placebo tablets. The study took place in an out-patient setting, with three times weekly exercise sessions at a Sports Centre. After 6 months the placebo group showed no change in plasma glucose, cholesterol and blood pressure. The subjects receiving gliclazide showed improved glucose levels (mean fasting plasma glucose levels fell from 5.8 to 5.1 mmol/l, p < 0.05) but no significant change in plasma cholesterol or blood pressure. The healthy living group, after exclusion of four non-compliant subjects, showed no change in glucose levels, but a decreased systolic blood pressure (fall in mean from 124 to 116 mmHg, p < 0.05) and plasma cholesterol levels (fall in mean from 5.2 to 4.5 mmol/l, p < 0.01). with an increase in HDL:LDL ratio (rise in mean from 0.39 to 0.46, p < 0.05). Subjects with impaired glucose tolerance may benefit in different ways from gliclazide and healthy living. The metabolic responses to each therapy may help to decrease the risk of developing diabetes and cardiovascular disease.

Adolescent↗
PubMed1992

Smooth muscle and epithelial cells express specific binding sites for the C1q component of complement.

In injury and inflammation, interactions of complement C1q with C1q receptors may provide attachment sites for cell localization and tissue regeneration. Cultured smooth muscle cells (58%), epithelial cells (26%), and endothelial cells (25%) attach to C1q-coated surfaces, while only 6% of cultured B cells (Raji) attach. Endothelial and Raji cells express C1q receptors, but C1q receptors (C1qR) on smooth muscle cells and epithelial cells have not previously been demonstrated. Evidence is provided that smooth muscle cells express an average of 1.5 x 10(6) C1qR/cell (K alpha = 10(8) M-1) and that epithelial cells express an average of 0.7 x 10(6) C1qR/cell (K alpha = 1.4 x 10(8) M-1). Binding properties of C1qR, and immunoreactivity to anti-C1qR antibodies, are characterized. The antibodies specifically recognize a 67-kDa component of smooth muscle cell lysates and inhibit cell attachment to C1q substrates. We conclude that distribution of C1qR may be ubiquitous; binding properties, size, and antigenicity of various C1qR may be related, but adhesive function may be tissue specific.

Animals↗
PubMed1992

Isolation of human tumor cells that produce cementum proteins in culture.

We have cultured cells from explants of a human cementum tumor. The cells obtained were multipolar, they formed network-like structures and they were alkaline-phosphatase positive. Immunostaining and Western blots using specific antibodies revealed that these cells produced bone sialoprotein and collagen types I and V, and they also mineralized in vitro. Conditioned medium was mitogenic to fibroblasts and mitogens present were separated by heparin-affinity chromatography. Based on affinity to heparin and antibody-inhibition studies, the heparin fractions were shown to contain cementum-derived growth factor, platelet-derived growth factor and fibroblast growth factors. The cementum tumor cells, but not gingival fibroblasts, were stained positively by an antibody to cementum-derived attachment protein. The attachment protein was separated by immunoaffinity chromatography, and Western blots revealed that the preparation contained 56-kDa and 43-kDa proteins as major bands. Cells pulse-labeled with radioactive amino acids contained a 43-kDa protein as the major component; however, this protein was absent after a cold chase in the presence of cycloheximide, but 56-kDa, 39-kDa and 26-kDa species became prominent. These data indicated that the 56-kDa cementum attachment protein is derived from a 43-kDa precursor. Our data show that the cells cultured from the cementum tumor represent cementum cells capable of synthesizing and secreting cementum proteins in culture.

Alkaline Phosphatase↗
PubMed1992

Isolation and partial characterization of a growth factor from human cementum.

Cementum is the mineralized interface through which collagen fibers of periodontal connective tissues are anchored onto the tooth surface. We have isolated and partially characterized a mitogenic factor from human cementum which has properties different from other growth factors. Cementum was harvested from healthy human teeth, extracted in 1.0 M CH3COOH and mitogenic activities were fractionated by heparin-affinity chromatography. Proteins eluted by 0.4-0.6 M NaCl, which contained most of the cementum mitogenic activity, were precipitated by trichloroacetic acid and resolved by HPLC through ion-exchange and reverse-phase columns. NaDodSO4-polyacrylamide gel electrophoresis revealed that the purified preparation contained a M(r) 23,000 protein and this protein was associated with mitogenic activity. The purified cementum-derived growth factor (CGF) was active alone, but at suboptimal concentrations its activity was potentiated by small quantities of plasma-derived serum and epidermal growth factor (EGF). The activity was resistant to heat, but it was destroyed by trypsin digestion. Reduction and alkylation destroyed the mitogenic activity, however electrophoretic mobility was not affected. Binding of EGF to fibroblast membranes was not affected by the CGF and assays to detect platelet-derived growth factor were negative. These characteristics indicated that CGF is a distinct molecular species. Our data show that cementum contains several mitogenic factors and that CGF is the major cementum mitogen.

Cell Division↗
PubMed1992

Production of a monoclonal antibody to an attachment protein derived from human cementum.

Cementum is the mineralized structure that covers the surface of the roots of teeth; it serves as the attachment site for collagen fibers of adjacent soft connective tissues. Very little is known about how cementum formation is regulated or how it affects other periodontal structures. We have raised a monoclonal antibody that may aid in studies to determine the biology and function of cementum. Mice were immunized with a 55-kDa attachment protein partially purified from human cementum and a monoclonal antibody, H166, was produced. Incubation of tissue sections with this antibody and fluorescein isothiocyanate-conjugated secondary antibody revealed that it immunostains cementum but not dentin, gingiva, or periodontal ligament. Alveolar bone did not bind the antibody, although a few paravascular cells were positive. Long bones, kidney, liver, skin, and several other tissues were negative. Protein fractions separated from cementum extracts by binding to immobilized H166 column contained 55-, 49-, 39-, 29- to 31-, and 23- to 26-kDa components that cross-reacted with the antibody in Western blots; these components were previously shown to be derived from a common precursor. We conclude that the antibody recognizes a group of proteins related to 55-kDa attachment protein in cementum. Our data show that the antibody could serve as a marker for cementum.

Animals↗
PubMed1992

Can life-styles of subjects with impaired glucose tolerance be changed? A feasibility study.

Thirty-one subjects with impaired glucose tolerance were randomly allocated to a group receiving advice to improve their diet and physical activity levels over 6 months (n = 23) or to a control group (n = 8). At 6 months, 18 of the 23 subjects receiving 'healthy living' advice were re-examined (five subjects had withdrawn). Fourteen of the 18 subjects showed an alteration in diet or an increase in exercise. The 18 subjects re-evaluated showed a reduction in systolic blood pressure (118 +/- 15 vs 124 +/- 15 mmHg, p less than 0.05) and decrease in total plasma cholesterol (4.5 +/- 1 vs 5.2 +/- 1 mmol l-1, p less than 0.01) and LDL-cholesterol levels (2.8 +/- 0.9 vs 3.2 +/- 0.9 mmol l-1, p less than 0.05). Plasma glucose levels were unchanged. One subject withdrew from the control group. At 6 months, the seven control subjects examined showed no significant change in metabolic parameters, with little measurable change in diet or exercise. At 2 years, 17 of the 23 'healthy living' subjects were reassessed. Nine of the subjects had continued to exercise or maintained a decreased weight compared to baseline. Fasting plasma glucose levels had increased (6.0 +/- 1.2 vs 5.5 +/- 0.6 mmol l-1, p less than 0.05), with the only continued improvement being a reduced LDL level (2.8 +/- 0.7 vs 3.1 +/- 0.9 mmol l-1, p less than 0.05). At 2 years, a similar proportion of the control group were taking regular exercise compared with the 'healthy living' group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Diagnostic characteristics of crevicular fluid aspartate aminotransferase (AST) levels associated with periodontal disease activity.

During a 2-year period pocket depth, probing attachment level, gingival index, and crevicular fluid aspartate aminotransferase (AST) levels were monitored in 25 previously treated periodontitis patients. Probing attachment level change was used retrospectively to identify sites where active periodontal destruction had occurred. The ability of crevicular fluid AST activities at 600, 800, 1000, and 1200 microIU levels to recognize active disease was investigated. Probing attachment level changes observed support the concept that the pattern of periodontal disease activity is episodic and infrequent. A loss of greater than or equal to 2 mm was found at 11% of all studied sites, whereas a gain of greater than or equal to 2 mm was noticed for 15% of sites. 2 subjects had 3 teeth that lost greater than or equal to 2 mm of attachment, whereas 15 subjects demonstrated no teeth with disease activity. The remaining 8 subjects had 1 or 2 sites that lost greater than or equal to 2 mm of attachment. Bayes's theorem and ROC curves were used to exemplify the sensitivity and the specificity of AST assessments. The AST 800 microIU demonstrated a sensitivity of 0.93 and specificity 0.68 and an odds ratio of 15.4 for attachment loss greater than or equal to 2 mm. Under the conditional probability of either 50%, 25% or 10% active disease prevalence, AST 800 microIU has a predictability of 73%, 50% and 24% respectively.

Aspartate Aminotransferases↗