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C W Cutler

Publications and source records attributed to C W Cutler.

At least 19 recordsLinked to original sources
PubMed2006

Oral mucosal expression of HIV-1 receptors, co-receptors, and alpha-defensins: tableau of resistance or susceptibility to HIV infection?

The basic premise of whether transmission of HIV-1 through the oral mucosa actually occurs, and through what route, is a topic of intense interest. Our work has focused on HIV-1 receptors/co-receptors and alpha-defensin-1 in situ in human gingiva. Regardless of HIV-1 infection, the role that C-type lectin receptors might play in periodontal pathogenesis is of great interest. We have shown that the gingival lamina propria, when inflamed, becomes increasingly infiltrated with DC-SIGN+MR+ dermal dendritic cells (DDCs), while the inflamed epithelium shows a decrease in Langerin+ Langerhans cells (LCs). Moreover, DDCs and LCs contribute to the mature CD83+ DC pool in situ, and form immune conjugates with CD4+ T-cells in the lamina propria (Jotwani and Cutler, 2003). This raises the intriguing possibility that oral mucosal DCs may be involved in HIV-1 transfer to T-cells in situ. However, this possibility is tendered by the challenges faced by the virus in gaining access to oral mucosal immune cells, including their ability to survive the salivary defenses, cross the mucosal barrier, resist inactivation by alpha-defensins, and overcome the paucity of co-receptor CCR5 in (healthy) oral mucosa (i.e., required for productive infection [Jotwani et al., 2004]). To date, there is little evidence of direct infection by HIV-1 of oral mucosal DCs/T cells and other cells in situ. Abbreviations used in this paper: CP, chronic periodontitis; CCR5, chemokine receptor 5; CXCR4, C-X-C receptor 4; DCs, dendritic cells; DC-SIGN, DC-specific ICAM-3 grabbing non-integrin; DDC, dermal dendritic cells; LCs, Langerhans cells; LP, lamina propria; MR, mannose receptor.

Cell Adhesion Molecules↗
PubMed2006

Dendritic cells at the oral mucosal interface.

The mucosal lining of the respiratory and digestive systems contains the largest and most complex immune system in the body, but surprisingly little is known of the immune system that serves the oral mucosa. This review focuses on dendritic cells, particularly powerful arbiters of immunity, in response to antigens of microbial or tumor origin, but also of tolerance to self-antigens and commensal microbes. Although first discovered in 1868, the epidermal dendritic Langerhans cells remained enigmatic for over a century, until they were identified as the most peripheral outpost of the immune system. Investigators' ability to isolate, enrich, and culture dendritic cells has led to an explosion in the field. Presented herein is a review of dendritic cell history, ontogeny, function, and phenotype, and the role of different dendritic cell subsets in the oral mucosa and its diseases. Particular emphasis is placed on the mechanisms of recognition and capture of microbes by dendritic cells. Also emphasized is how dendritic cells may regulate immunity/tolerance in response to oral microbes.

Animals↗
PubMed2004

Increase in HIV receptors/co-receptors/alpha-defensins in inflamed human gingiva.

Transmission of HIV-1 through the oral cavity is considered to be a rare event. To identify factors in resistance/susceptibility to oral HIV-1 infection, we analyzed expression in human gingiva of HIV-1 receptors Langerin, DC-SIGN, MR, and GalCer, HIV-1 co-receptors CCCR5, CXCR4, and anti-microbial protein alpha-defensin-1. Our results show that healthy gingiva is infiltrated with cells expressing all HIV-1 receptors tested; however, there are very few CCR5(+) cells and a complete absence of CXCR4(+) cells in the lamina propria. In chronic periodontitis (CP), DC-SIGN, MR, CXCR4, and CCR5 increase, but this was accompanied by a ten-fold increase in alpha-defensin-1 mRNA. The CCR5(+) cells were revealed to be T-cells, macrophages, and dermal dendritic cells. Moreover, epithelial expression of GalCer and CXCR4 together was not apical and showed no trend with underlying inflammation. Thus, low expression of HIV-1 co-receptors in health and high expression of alpha-defensin during CP may comprise endogenous factors that provide protection from oral HIV-1 infection.

Adult↗
PubMed2003

Multiple dendritic cell (DC) subpopulations in human gingiva and association of mature DCs with CD4+ T-cells in situ.

Gingival epithelium is a site of active trafficking of Langerhans cells (LCs), while the lamina propria in chronic periodontitis (CP) contains CD83+ mature dendritic cells (mDCs) and CD4+ T-cells. The immune cells that contribute to the mDCs, and whether mDCs engage with T-cells in situ, are unclear. Using several immunohistochemical approaches, combined with fluorescence-, light-, and scanning laser confocal-microscopy, we show that, in addition to LCs, the gingiva contains dermal DCs (DDCs) in the lamina propria; moreover, DDCs increase in number during CP. Furthermore, DDCs, LCs, and B-cells co-express CD83 in CP and contribute to the mDC pool. Double-staining for CD83 and CD4 revealed that mDCs associate with clusters of CD4+ T-cells in the lamina propria. Analysis of these data suggests that multiple DC subsets mature in the gingiva and that mature DCs engage in antigen presentation with T-cells in chronic periodontitis.

Adult↗
PubMed2001

Lipopolysaccharides from distinct pathogens induce different classes of immune responses in vivo.

The adaptive immune system has evolved distinct responses against different pathogens, but the mechanism(s) by which a particular response is initiated is poorly understood. In this study, we investigated the type of Ag-specific CD4(+) Th and CD8(+) T cell responses elicited in vivo, in response to soluble OVA, coinjected with LPS from two different pathogens. We used Escherichia coli LPS, which signals through Toll-like receptor 4 (TLR4) and LPS from the oral pathogen Porphyromonas gingivalis, which does not appear to require TLR4 for signaling. Coinjections of E. coli LPS + OVA or P. gingivalis LPS + OVA induced similar clonal expansions of OVA-specific CD4(+) and CD8(+) T cells, but strikingly different cytokine profiles. E. coli LPS induced a Th1-like response with abundant IFN-gamma, but little or no IL-4, IL-13, and IL-5. In contrast, P. gingivalis LPS induced Th and T cell responses characterized by significant levels of IL-13, IL-5, and IL-10, but lower levels of IFN-gamma. Consistent with these results, E. coli LPS induced IL-12(p70) in the CD8alpha(+) dendritic cell (DC) subset, while P. gingivalis LPS did not. Both LPS, however, activated the two DC subsets to up-regulate costimulatory molecules and produce IL-6 and TNF-alpha. Interestingly, these LPS appeared to have differences in their ability to signal through TLR4; proliferation of splenocytes and cytokine secretion by splenocytes or DCs from TLR4-deficient C3H/HeJ mice were greatly impaired in response to E. coli LPS, but not P. gingivalis LPS. Therefore, LPS from different bacteria activate DC subsets to produce different cytokines, and induce distinct types of adaptive immunity in vivo.

Animals↗
PubMed2001

Mature dendritic cells infiltrate the T cell-rich region of oral mucosa in chronic periodontitis: in situ, in vivo, and in vitro studies.

Previous studies have analyzed the lymphoid and myeloid foci within the gingival mucosa in health and chronic periodontitis (CP); however, the principal APCs responsible for the formation and organizational structure of these foci in CP have not been defined. We show that in human CP tissues, CD1a(+) immature Langerhans cells predominantly infiltrate the gingival epithelium, whereas CD83(+) mature dendritic cells (DCs) specifically infiltrate the CD4(+) lymphoid-rich lamina propria. In vivo evidence shows that exacerbation of CP results in increased levels of proinflammatory cytokines that mediate DC activation/maturation, but also of counterregulatory cytokines that may prevent a Th-polarized response. Consistently, in vitro-generated monocyte-derived DCs pulsed with Porphyromonas gingivalis strain 381 or its LPS undergo maturation, up-regulate accessory molecules, and release proinflammatory (IL-1beta, PGE(2)) and Th (IL-10, IL-12) cytokines. Interestingly, the IL-10:IL-12 ratio elicited from P. gingivalis-pulsed DCs was 3-fold higher than that from Escherichia coli-pulsed DCs. This may account for the significantly (p < 0.05) lower proliferation of autologous CD4(+) T cells and reduced release of IFN-gamma elicited by P. gingivalis-pulsed DCs. Taken together, these findings suggest a previously unreported mechanism for the pathophysiology of CP, involving the activation and in situ maturation of DCs by the oral pathogen P. gingivalis, leading to release of counterregulatory cytokines and the formation of T cell-DC foci.

Adult↗
PubMed2001

Prior exposure of mice to Fusobacterium nucleatum modulates host response to Porphyromonas gingivalis.

Multiple periodontal pathogens sequentially colonize the subgingival niche during the conversion from gingivitis to destructive periodontal disease. An animal model of sequential immunization with key periodontal pathogens has been developed to determine whether T- and B-lymphocyte effector functions are skewed and fail to protect the host from pathogenic challenge. The present study was performed to evaluate the immunomodulatory effect of exposure to Fusobacterium nucleatum prior to Porphyromonas gingivalis. Group 1 (control) mice were immunized with phosphate-buffered saline, group 2 were immunized with F. nucleatum prior to P. gingivalis and group 3 were immunized with P. gingivalis alone. All the T-cell clones derived from group 2 demonstrated type 2 helper T-cell clone (Th2 subsets), whereas those from group 3 mice demonstrated Th1 subsets. Exposure of mice to F. nucleatum prior to P. gingivalis interfered with the opsonophagocytosis function of sera against P. gingivalis. In adoptive T-cell transfer experiments, in vivo protective capacity of type 2 helper T-cell clones (Th2) from group 2 was significantly lower than type 1 helper T-cell clones (Th1) from group 3 against the lethal dose infection of P. gingivalis. Western blot analysis indicated a different pattern of recognition of P. gingivalis fimbrial proteins between sera from group 2 and group 3. In conclusion, these studies suggest that exposure of a host to F. nucleatum prior to the periodontal pathogen P. gingivalis modulates the host immune responses to P. gingivalis at the humoral, cellular and molecular levels.

Adjuvants, Immunologic↗
PubMed2000

Clinical benefits of oral irrigation for periodontitis are related to reduction of pro-inflammatory cytokine levels and plaque.

BACKGROUND: Although a growing body of evidence indicates that oral irrigation with water has therapeutic benefits in periodontitis, the mechanisms of action have not been elucidated. The aims of this study were: (1) to analyze the effects of oral irrigation (Water Pik Oral Irrigator) on the clinical signs of adult periodontitis (AP) and on the levels of interleukin-1 beta (IL-beta), prostaglandin-E2 (PGE2), interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) in GCF, and (2) to analyze the influence of the periodontitis-related IL-1 genotype (IL-1GT) on these variables. METHOD: A single-center, blinded study in otherwise healthy humans (n= 52) with localized mild to moderate AP was carried out, using the following groups: group A (n= 12), no oral hygiene for 14 days; group B (n=20), routine oral hygiene (ROH) for 14 days; group C (n=20), supra-gingival oral irrigation plus ROH for 14 days. Group A patients were crossed-over to group C for 14 days (=day 28) after a professional prophylaxis. Group assignment was randomized by a coin toss, with the exception of group A subjects, who were self-selected as per recommendations of the internal review board for human subjects. GCF was sampled from 3 study teeth per patient and analyzed for IL-1 beta, PGE2, IL-10 and IFN gamma by ELISA on days 0, 7, 14 and 28. Probing pocket depths (PPD), clinical attachment levels (CAL), bleeding on probing (BOP), gingival index (GI) and plaque index (PI) were measured by a calibrated examiner (TWS) on days 0, 14 and 28. Analysis of covariance was performed using SAS 6.12 and Proc Mixed with group and IL-1GT as the factors and the baseline levels as the covariate, with output being least squares means and least significant difference (LSD). Significant differences were declared if the p-value for the F-statistic was < or =0.05. RESULTS: Oral irrigation plus ROH resulted in a significant reduction in PPD, BOP, GI and PI, as well as IL-beta levels by 7 days and PGE2 levels by 14 days, relative to ROH or no oral hygiene. Interestingly, decreased IL-1 beta levels in patients using oral irrigation plus ROH was accompanied by a trend for increased levels of the "anti-inflammatory" cytokine IL-10. ROH reduced GI, BOP and PI, and PGE2 levels by 14 days, but had no effect on IL-1 beta or IL-10 levels relative to no oral hygiene. The effects of no oral hygiene were reversed by a prophy followed by oral irrigation plus ROH for 14 days. No clinical differences were evident between IL-1 GT (+) patients (n= 1) and GT (-) patients (n=40), but the former had significantly elevated levels of GCF IL-10 and borderline increases in IL-1 beta (p=0.07). CONCLUSIONS: Oral irrigation with water for 14 days had an improved therapeutic benefit for AP over that of routine oral hygiene alone and this improvement was accompanied by a down-modulation of the pro-inflammatory cytokine profile in GCF.

Adult↗
PubMed2000

Comparative radiopacity of tetracalcium phosphate and other root-end filling materials.

AIM: This study compared the radiopacity of tetracalcium phosphate (TTCP) and 11 root-end filling materials relative to human dentine. METHODOLOGY: Specimens of 2 mm thickness and a graduated aluminium stepwedge were placed on dental X-ray films and exposed to an X-ray beam. The optical densities of the specimens and aluminium steps were measured. The optical densities of the specimens were correlated to the equivalent thickness of aluminium with a regression analysis equation. The equation was used to calculate the equivalent aluminium thickness of each of the specimens. RESULTS: Nine of the materials were found to be of acceptable radiopacity (at least 2 mm Al more radiopaque than dentine). TCCP and two of the glass-ionomer compounds were found to have insufficient radiopacity to be radiographically distinguishable from human dentine. CONCLUSIONS: All the materials were found to be distinguishable radiographically from dentine, except for Vitrebond, TTCP and Ketac-Fil. Amalgam was the most radiopaque material and Ketac-Fil was the least radiopaque material tested.

Absorptiometry, Photon↗
PubMed2000

In vitro evidence that lipopolysaccharide of an oral pathogen leaks from root-end filled teeth.

AIM: The ability to achieve a complete apical seal of the root canal system is thought to be important in the success of non-surgical and surgical endodontics. The aim of this study was to establish whether or not root-end filled teeth allow leakage of lipopolysaccharide (LPS) from a known oral pathogen in vitro. METHODOLOGY: Lipopolysaccharide (LPS) from a virulent strain of Prophyromonas gingivalis (P. gingivalis) (A7436 from patient with refractory periodontitis), was isolated by the Westphall and Jann technique, dialysed extensively, lyophilyzed, resuspended in distilled water and analysed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Root canals from 10 teeth were instrumented endodontically and the apical 3 mm of resected roots were filled with gutta-percha. The teeth were mounted in 12 mL polypropylene vials by using sticky wax and root surfaces were covered with two layers of nail varnish. Teeth were filled with 3.3 mg mL-1 LPS and the vials filled with 11 mL of Tris Buffered Saline (TBS) containing 0.05% sodium azide. Both positive and negative controls were run in parallel with the experimental specimens. Aliquots were removed each day and subjected to slot blot analysis to quantitate the amount of LPS that had leaked into the bottom of the vials. The density of slots was analyzed using a laser densitometer and regression analysis was used to generate a standard curve, confidence intervals and experimental values. RESULTS: The data indicated that teeth obturated apically with gutta-percha leaked, whilst no LPS leakage was detected in teeth covered completely with nail varnish (P < 0.05). CONCLUSIONS: In vitro teeth with gutta-percha root-end fills can permit leakage of LPS from an identified oral pathogen.

Apicoectomy↗
PubMed2000

Pathophysiological relationships between periodontitis and systemic disease: recent concepts involving serum lipids.

Periodontitis has been traditionally regarded as a chronic inflammatory oral infection. However, recent studies indicate that this oral disease may have profound effects on systemic health. The search for cellular/molecular mechanisms linking periodontitis to changes in systemic health and systemic physiology has resulted in the evolution of a new area of lipid research establishing linkages between existing multidisciplinary biomedical literature, recent observations concerning the effects of serum lipids on immune cell phenotype/function, and a heightened interest in systemic responses to chronic localized infections. There appears to be more than a casual relationship between serum lipid levels and systemic health (particularly cardiovascular disease, diabetes, tissue repair capacity, and immune cell function), susceptibility to periodontitis, and serum levels of pro-inflammatory cytokines. In terms of the potential relationship between periodontitis and systemic disease, it is possible that periodontitis-induced changes in immune cell function cause metabolic dysregulation of lipid metabolism through mechanisms involving proinflammatory cytokines. Sustained elevations of serum lipids and/or pro-inflammatory cytokines may have a serious negative impact on systemic health. The purpose of this paper is to present the background, supporting data, and hypotheses related to this concept. As active participants in this emerging and exciting area of investigation, we hope to stimulate interest and awareness among biomedical scientists and practitioners.

Cytokines↗
PubMed1999

Evidence and a novel hypothesis for the role of dendritic cells and Porphyromonas gingivalis in adult periodontitis.

We have proposed a novel overall hypothesis and approach to understanding the pathophysiology of adult periodontitis, one of the most common diseases that afflicts the US population. While mortality of the dentition is the most familiar outcome of adult periodontitis, its links with other more severe diseases, including coronary artery disease, respiratory diseases and pre-term labor, cannot be ignored. We have called attention to the many intriguing parallels between adult periodontitis and contact hypersensitivity (CHS). CHS is among the most common of dermatoses that afflicts mankind and one of the most intensively studied of in vivo immune responses. Both adult periodontitis and CHS target the host integument (gingiva or skin) and appear to involve the activation and sensitization of similar subsets of antigen capture and presenting cells, the dendritic cells (DCs), as well as similar T cell subsets. DCs have been termed "nature's adjuvant", being more efficient at antigen-presentation than macrophages or B cells and the only antigen-presenting cells that can stimulate naïve T cells to proliferate. This immunostimulatory capacity can also have detrimental effects for the host, as typified by graft-vs.-host disease and CHS responses. Both AP and CHS involve a predominantly destructive T cell response mediated by both regulatory and effector T cells. In the present paper, we show intriguing evidence that Porphyromonas gingivalis is a unique pathogen in this regard, able to infect, sensitize and activate DCs in vitro and, probably, in situ. Many questions about the role of P. gingivalis-sensitized DCs in adult periodontitis, and of the parallels between adult periodontitis and CHS, however, remain to be answered.

Adult↗
PubMed1999

Heightened gingival inflammation and attachment loss in type 2 diabetics with hyperlipidemia.

BACKGROUND: Our previous studies in diabetic (DB) rats suggest that hyperlipidemia may cause a dysregulation of the cellular and local cytokine response to periodontitis (AP). The objective of the present study was to determine if diabetes has a similar dysregulatory effect on the gingival response to AP in humans. METHODS: Peripheral blood, as well as gingival tissue (GT) and gingival crevicular fluid (GCF), was obtained from a total of 35 patients who were categorized into the following groups based on level of diabetic (type 2) control and presence or absence of adult periodontitis (AP): group 1, systemically and periodontally healthy (n = 6); group 2, systemically healthy with adult periodontitis (n = 7); group 3, well-controlled diabetes and periodontally healthy (n = 6); group 4, well-controlled diabetes with adult periodontitis (n = 5); group 5, poorly controlled diabetes and periodontally healthy (n = 5); group 6, poorly controlled diabetes and adult periodontitis (n = 6). All subjects were given a thorough periodontal examination, including probing depths (PD), clinical attachment levels (CAL), gingival index (GI), plaque index (PI), and vertical bitewing radiographs. Blood studies included levels of glycated hemoglobin (HbA1c), triglycerides (TG), cholesterol (CHL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). The levels of interleukin-1 beta (IL-1beta) in GCF and GT, interleukin-6 (IL-6), and platelet-derived growth factor AB (PDGF-AB) in GT from patients in each experimental group were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Our results indicate that all clinical indices except PI were significantly elevated in the poorly controlled and well-controlled diabetics, compared to systemically healthy patients, but only in the subjects without preexisiting AP (Tukey's multiple comparisons, P <0.05). Pairwise linear regression analysis revealed significant (P <0.01) positive associations between periodontal inflammation (PD, CAL, PI, GI) and levels of GCF IL-1beta, GT IL- 1beta GT IL-6, but not GT PDGF; moreover, GT IL-6 levels were significantly associated (P<0.05) with GT IL-1beta. As TG levels increased in the non-AP patients (group 1 < group 3 < group 5), there was a trend, not significant, for increased GCF IL-1beta levels and increased gingival inflammation. Interestingly, periodontitis resulted in increased PDGF-AB levels in the gingiva of systemically healthy and well-controlled diabetes patients, but this increase was obtunded in poorly controlled diabetes patients. CONCLUSIONS: This confirms our earlier work in the diabetic rat model. These studies indicate that decreased metabolic control in type 2 diabetics results in increased serum triglycerides and has a negative influence on all clinical measures of periodontal health, particularly in patients without preexisting periodontitis. Levels of the cytokine IL- 1beta showed a trend for increasing as diabetic control diminished. In contrast, levels of the growth factor PDGF, which normally increase in periodontitis, decreased in poorly controlled diabetics with periodontitis. These studies suggest a possible dysregulation of the normal cytokine/growth factor signaling axis in poorly controlled type 2 diabetics that may contribute to periodontal breakdown/diminished repair.

Adult↗
PubMed1999

Association between periodontitis and hyperlipidemia: cause or effect?

BACKGROUND: Epidemiological studies suggest a relationship between periodontitis and coronary artery disease, but the mechanism has not been established. Recent studies in animals indicate that low dose endotoxin, as in a gram-negative infection, can induce hyperlipidemia and myeloid cell hyperactivity. The association between periodontitis, systemic exposure to Porphyromonas gingivalis, lipopolysaccharides (LPS), and hyperlipidemia has not been examined in humans. METHODS: Sera were obtained from 26 adult periodontitis patients and 25 healthy control (C) subjects selected from patients and staff. Serum antibodies against Porphyromonas gingivalis and its LPS were analyzed by enzyme-linked immunosorbent assay (ELISA) and Western blotting, respectively. Serum triglycerides (TG) and cholesterol (CHOL) were assayed by a commercial laboratory. The associations between AP and blood levels of TG, CHOL, and anti-P. gingivalis whole cells and LPS were examined by logistic regression analysis. Peripheral blood polymorphonuclear leukocytes (PMNs) from 6 healthy fasted donors were incubated with purified TG (0.1 mg/ml) for 2 hours at 37 degrees C, stimulated with 100 ng/ml P. gingivalis LPS, and the release of IL-1beta measured by ELISA. RESULTS: The presence of periodontitis was significantly associated with age (odds ratio = 3.5, P = 0.04), elevated TG levels (odds ratio = 8.6, P = 0.0009), elevated CHOL levels (odds ratio = 7, P = 0.004), elevated ELISA titer (odds ratio = 35, P = 0.003) and reactivity with P. gingivalis LPS (odds ratio = 41, P = 0.001). PMNs from all 6 healthy patients released modest levels of IL-1beta (10 to 60 pg/ml) when stimulated with 100 ng/ml P. gingivalis LPS. Addition of TG resulted in a significant increase (P <0.05) in IL- 1beta secreted that ranged from 7 to 150% over LPS alone. No IL-1beta was elicited by TG or vehicle alone. CONCLUSIONS: The results of this study indicate the presence of a significant relationship between periodontitis, hyperlipidemia, and serum antibodies against P. gingivalis LPS that warrants further examination in a larger patient population. Furthermore, these studies indicate that elevated triglycerides are able to modulate IL-1beta production by PMNs stimulated with P. gingivalis LPS.

Adult↗
PubMed1998

Sublocalization of the Papillon-Lefevre syndrome locus on 11q14-q21.

Papillon-Lefevre syndrome (PLS) is an autosomal recessive form of palmoplantar ectodermal dysplasia, characterized by palmoplantar hyperkeratosis and severe early-onset periodontitis. The presence of severe periodontitis distinguishes PLS from other palmoplantar keratodermas. As part of our efforts to study the genetic basis of periodontitis susceptibility, we performed a genome-wide search to identify major loci for PLS in 44 individuals (14 affected) from 10 consanguineous PLS families. We have identified evidence for linkage of a PLS gene on 11q14-q21. A maximum two-point logarithm of the odds (LOD) score of 8.24 was obtained for D11S1367 at a recombination fraction of theta=0.00. Multipoint analysis resulted in a LOD score of 10.45 and placed the gene for PLS within a 4-5 cM genetic interval. This genetic interval, flanked by D11S4197 and D11S931, contains more than 50 cDNAs and 200 expressed sequence tags (ESTs). This refinement of the candidate region for a PLS gene is in agreement with other recent reports of linkage for PLS to chromosome 11q14-q21 and should help in identification of the gene for PLS.

Chromosomes, Human, Pair 11↗
PubMed1998

Diabetes-induced impairment of macrophage cytokine release in a rat model: potential role of serum lipids.

Diabetes (type I and type II) affects approximately 13 million people in the United States. Delayed and incomplete healing of wounds can be a major problem for diabetic patients. Macrophages are an important cell in the complex process of wound repair representing the major source of cytokines throughout the wound healing process. Cytokines mediate many of the cellular responses critical to timely wound repair. It has been suggested that diabetes impairs wound healing through disruption of local cytokine production. We previously demonstrated that platelet-derived growth factor B chain (PDGF-B) levels are deficient at the wound site of diabetic rats. In the present study, we measured the levels of several marker cytokines released from cultured peritoneal macrophages of diabetic, nondiabetic hyperlipidemic, and normal rats. The diabetic condition was associated with a generalized reduction of macrophage cytokine release. Nondiabetic hyperlipidemic animals demonstrated similar cytokine reduction supporting the hypothesis that elevated serum lipids are the primary determinants of diabetes-induced reductions in macrophage cytokine release. Thus, manipulation of serum lipids may be a therapeutically useful modality for controlling macrophage cytokine release in the inflammatory and/or wound environment.

Animals↗