Significance of salivary antibody in dental disease.
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Adult↗
Biomedical subjects
D J Smith
Publications and source records attributed to D J Smith.
Delivery of growth factor to wounds using a genetically engineered biological bandage.
Increasing the rate of wound healing of acute wounds and promoting the closure of chronic ulcers is an important goal in wound therapy. Growth factors have been shown to facilitate this process; however, the systems described for growth factor delivery are not ideal. In the present report we demonstrate the feasibility of a new method of delivering growth factors to the wound site using a genetically engineered biological bandage. The bandage consists of keratinocytes (SCC-13 cells) that are engineered by gene transfer to produce high levels of bovine growth hormone (bGH). bGH was selected for these studies because it can be easily distinguished from rat and human growth hormone in wound fluids and culture medium. The bGH-producing cells are contained and maintained in serum-free medium inside an envelope composed of a low protein binding, 0.2 micron pore size, polysulfone membrane. The genetically engineered cells cannot escape from the bandage, but the bGH is freely released into the surrounding culture medium. When placed onto a full-thickness, surgically generated wound on rats, the cells within the bandage continue to produce and release bGH into the wound for at least 3 days. This system is a safe and reliable way of providing real-time delivery of any desired biomolecule into the wound site.
Animals↗
5-HT3 receptors which modulate [3H]5-HT release in the guinea pig hypothalamus are not autoreceptors.
The 5-HT3 agonist 2-methyl-5-HT had previously been shown to enhance the electrically evoked release of [3H]5-HT from preloaded slices of the guinea pig brain. In the present study, 2-methyl-5-HT (1 microM) was also found to increase the K+ evoked release of [3H]5-HT from preloaded slices of the guinea pig hypothalamus and this effect was blocked by the selective 5-HT3 antagonist ondansetron. In the presence of tetrodotoxin, the enhancement of the K(+)-evoked release of [3H]5-HT by 2-methyl-5-HT in hypothalamus slices was blocked, thus suggesting that the 5-HT3 receptors mediating this effect are not located directly on 5-HT terminals. In agreement with this, 2-methyl-5-HT did not alter the K(+)-evoked release of [3H]5-HT in a synaptosomal preparation of the same brain structure, even at a concentration 10-fold greater than that used in the slices. Taken together, these data indicate that these facilitatory 5-HT3 receptors are not located on 5-HT terminals in the guinea pig hypothalamus and therefore are not autoreceptors.
Animals↗
Environmental hazards and health.
Significant health hazards to the traveller arise from altitude, heat, cold and water. Altitude-induced illness encompasses the benign but common syndrome of acute mountain sickness and also life-threatening pulmonary and cerebral oedema; inadequate acclimatization and rapid ascent are important precipitating factors in each case. Prophylaxis and up to date choices of treatment are discussed in the context of underlying physiological changes. Heat illnesses include exhaustion and heat stroke; they result from increased core temperature and/or physiological responses including peripheral vasodilation and sweating. Preventive measures include acclimatization, ample water without added salt, and matching dress and exercise to the environment. Cold environments pose risk of hypothermia and local cold injury which include frostbite and non-freezing cold injury; as frostnip is only diagnosed after treatment, it is a category of limited usefulness. Prevention of each disorder requires correct clothing and equipment and good training. Other hazards include immersion, and flying too soon after diving.
Altitude Sickness↗
Ketamine contains benzethonium.
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Benzethonium↗
Correlation of the local and systemic cytokine response with clinical outcome following thermal injury.
Eighty-eight patients with acute thermal injury were evaluated. Forty-eight hours after injury, TNF, IL-6, and IL-8 were significantly present in the systemic circulation, lung, normal skin, and thermally injured skin. The presence of TNF, IL-6, and IL-8 proteins in the lung, normal skin, and thermally injured skin were associated with TNF, IL-6, and IL-8 mRNA upregulation. Logistic regression analysis controlling for the Abbreviated Burn Severity Index demonstrated that the presence of IL-8 in the lung was associated with early pulmonary physiologic dysfunction (p = 0.006) and nosocomial pulmonary infection (p = 0.040). We conclude that acute thermal injury initiates an early systemic, lung, and skin response involving TNF, IL-6, and IL-8. The TNF, IL-6, and IL-8 protein present in the lung and skin in response to acute thermal injury are generated locally and do not originate from the systemic cytokine pool. The lung cytokine response to acute thermal injury may initiate local organ failure.
Adult↗
Microbiology and healing of the occluded skin-graft donor site.
Delayed healing of skin-graft donor sites may be costly and life-threatening, especially in patients with large body surface area burns. A donor site dressing should maximize the ability of the wound to heal without increasing the risk of local infection, systemic infection, or both. Specifically, the possibility of a secondary infection may either slow the healing process or ultimately convert the donor site into a full-thickness skin loss. A number of materials ranging from gauze to biologicals have been investigated for use as donor site dressings. The use of hydrocolloids for donor sites has been widely studied and has shown improved healing rates over the rates reported for conventional dressings. Our recent study using hydrocolloids confirmed earlier research that showed fewer infections and more rapid donor site healing.
Burns↗
Phenotypic differences in cytokine responsiveness of hypertrophic scar versus normal dermal fibroblasts.
The alteration of normal dermal fibroblast function that leads to the development of hypertrophic scar after thermal injury is unknown. To determine functional differences that might explain this process, fibroblasts were cultured from biopsies of post-thermal injury mature hypertrophic scars and patient-matched normal skin. The mitogenic responses of scar cells to fetal bovine serum, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and tumor necrosis factor alpha (TNF alpha) were determined and compared to normal skin cells. Collagen synthetic rate was also compared in the presence and absence of transforming growth factor beta 1 (TGF beta 1). Whereas both scar and normal cells responded with increased thymidine uptake to serum and cytokines, the stimulation to EGF and serum was significantly lower in scar cells. In contrast, synthesis of collagen, but not of non-collagenous proteins, was increased in scar relative to normal cells, both basally and when stimulated with low doses of TGF beta 1. Additionally, the fraction of protein synthesized as collagen was significantly higher in scar fibroblasts. These results suggest that fibroblasts from hypertrophic scars demonstrate stable phenotypic differences in cytokine responsiveness in comparison to cells from unaffected skin. The increased rate of collagen synthesis and decreased responsiveness to mitogens are consistent with the increased extracellular matrix content and decreased cellularity of hypertrophic scars.
Adolescent↗
Oral streptococcal colonization of infants.
The objective of this study was to determine the prevalence and proportions of different streptococcal species among the streptococcal flora during infancy. A total of 60 oral samples were collected by oral swabbing of the buccal mucosa and alveolar ridges of 18 infants before tooth eruption and from buccal and lingual surfaces of teeth after tooth eruption. A total of 549 isolates on mitis salivarius agar were speciated, principally by recently revised biochemical criteria of Kilian et al. Streptococcus mitis biovar 1 predominated, both in prevalence (89%) and proportion of oral streptococci recovered in each sample (median = 87% of streptococcal flora). Streptococcus salivarius was also prevalent (94%) but generally represented a small percentage of the total streptococcal flora (median = 3%). Streptococcus oralis and Streptococcus anginosus strains were detected in approximately one third of predentate and dentate infants in the first year of life. Streptococcus sanguis strains were not detected before tooth eruption, but could be detected in 7/14 of the infants with teeth. Thus, S. mitis constitutes the major component of the initially colonizing streptococcal microbiota of the young infant.
Alveolar Process↗
An unusual renal mass: ?Wegener's granulomatosis.
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Eye Diseases↗
Wound complications and treatment of the infected implantable cardioverter defibrillator generator.
Since 1980, the automatic implantable cardioverter defibrillator (ICD) has evolved as effective therapy for prevention of sudden cardiac death following documented sustained ventricular tachycardia or fibrillation. During a 5-year period, 412 ICD devices were implanted at the University of Michigan Hospitals with a wound complication rate of 4.1%. In this group, there were 13 infections, 3 erosions of the generator pocket, and 1 wound hematoma. Of the 16 patients with infection or erosion, 12 patients were treated with a rectus abdominis muscle flap closure and 4 with ICD generator removal. In 83% (n = 12) of the muscle flap patients, the wound healed uneventfully. Preoperative chest CT scanning was found to be helpful in identifying probable infection of the epicardial leads. In these cases, all hardware had to be removed to achieve resolution of the infection. We concluded that rectus abdominis muscle flaps were helpful in salvaging infected or exposed ICD generators in the absence of infected epicardial leads.
Bacterial Infections↗
Antigenicity and immunogenicity of a synthetic peptide derived from a glucan-binding domain of mutans streptococcal glucosyltransferase.
The immunogenicity and antigenicity of a multiply antigenic peptide construct containing four copies of the synthetic peptide TGAQTIKGQKLYFKANGQQVKG were measured in rodents and humans, respectively. The composition of this peptide construct (termed GLU) was derived from a major repeating sequence in the C-terminal region of mutans streptococcal glucosyltransferases that synthesize water-insoluble glucan (GTF-I). The GLU peptide elicited high levels of serum immunoglobulin G antibody to GLU after subcutaneous injection into Sprague-Dawley rats. These antisera also reacted with intact GTF isozymes from Streptococcus sobrinus and Streptococcus mutans (by enzyme-linked immunosorbent assay [ELISA] and Western blot [immunoblot] analyses) and with an 87-kDa glucan-binding protein from S. sobrinus (by Western blot). The synthesis of filter-retained glucan by GTF-Sd of S. sobrinus could be inhibited (30%) by preincubation with anti-GLU rat serum. Splenic and lymph node lymphocytes from rats injected once with S. sobrinus GTF isozymes demonstrated significant proliferation after 5 days of culture with GLU. The GLU peptide reacted with 4 of 29 human parotid saliva samples and 5 of 29 human serum samples (by ELISA). These results suggest that the GLU peptide contains B- and T-cell epitopes that are similar to those of intact mutans streptococcal GTFs and possibly certain other glucan-binding proteins as well. Furthermore, since antibody to this epitope(s) appears to inhibit GTF function, sequences within this peptide construct may have value for inclusion in a synthetic dental caries vaccine.
Adult↗
Emergence of immune competence in saliva.
Saliva contains essentially no IgA at birth. However, secretory immune responses to oral and non-oral microbial antigens emerge early in life. We have investigated the characteristics of these responses in salivas of infants less than 1 month through 4 years of age, using cross-sectional and longitudinal approaches. Antibody specificities (IgA, IgA1, and IgA2) were measured in ELISA and Western blot analysis to antigens of Streptococcus mitis and S. salivarius that colonize during the neonatal period. Antibodies reactive with S. sanguis and mutans streptococci, which colonize later in the infant's life, were also determined. Concurrent investigation of the oral flora of each infant was performed and related to the observed antibody specificities. The secretory nature of the immunoglobulins in these salivas was analyzed immunologically and chromatographically. The primary molecular form of salivary IgA was dimeric in all salivas tested. Both IgA subclasses were found, although a subset of infant salivas initially contained > 90% IgA1. IgM (> 1 microgram/ml) was detected in 58% of 3- to 17-week-old infants. By 2 months of age, salivas from most infants contained IgA antibody reactive with at least two S. mitis components. Many salivas also contained antibody reactive with S. salivarius components. By the end of the first year, most salivas contained IgA1 and IgA2 antibody to S. mitis antigens. Maturation of secretory responses in the second and third year was evidenced by the appearance of increased concentrations and additional specificities of salivary IgA antibodies to S. mitis antigens. Antibody to S. mitis, S. salivarius, and S. sanguis extracellular components was detected only after infection with the respective species.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
Identification of goat and mouse urinary metabolites of the pneumotoxin, 3-methylindole.
1. Urine from goats dosed i.v. with 3-methylindole (3MI; 15 mg/kg) or [methyl-14C] 3MI (15 mg/kg, 0.5 microCi/kg) contained at least 11 metabolites of 3MI. 2. Goat metabolized 3MI to sulfate conjugates of 4- or 7-hydroxy-3-methyloxindole, 5- or 6-hydroxy-3-methyloxindole, and 3,5- or 6-dihydroxy-3-methyloxindole; glucuronic acid conjugates of indole-3-carboxylic acid and 4- or 7-hydroxy-3-methyloxindole; and unconjugated 3-hydroxy-3-methyloxindole. Diastereoisomeric glucuronic acid conjugates of 3-hydroxy-3-methyloxindole were also identified in goat urine. 3. Urine from mice dosed i.p. with 3MI (400 mg/kg) or [ring-UL-14C] 3MI (400 mg/kg, 125 microCi/kg) contained at least six metabolites of 3MI. 4. Mice metabolized 3MI to glucuronic acid conjugates of 3,5- or 6-dihydroxy-3-methyloxindole, 5- or 6-hydroxy-3-methyloxindole, and indole-3-carboxylic acid; and unconjugated indole-3-carboxylic acid. Unconjugated 3-hydroxy-3-methyloxindole was identified in mouse urine in a previous report. 5. Both goats and mice metabolized 3MI to a mercapturate, 3-[(N-acetyl-L-cystine-S-yl)methyl]indole, which has been previously identified and was confirmed in this study. 6. 3-Methyloxindole was not identified in the urine of either goats or mice. 7. The major pathways of 3MI biotransformation in goats and mice is the formation of mono- and dihydroxy-3-methyloxindoles and their subsequent conjugation with glucuronic acid or sulfate. 8. There are no apparent qualitative differences in the biotransformation of 3MI between goats and mice that can account for their different sensitivities to 3MI-induced lung injury.
Animals↗
Effect of high concentration perflubron emulsion on platelet function.
Perfluorocarbon (PFC) and lipid emulsions (eg. Fluosol, Intralipid,) containing phospholipid have been reported to modify platelet function after intravenous infusion. Platelet activation might be responsible for the generation of mediators responsible for PFC-induced side effects. In view of this, we investigated the effect of a highly concentrated perfluorocarbon emulsion, containing 90% (w/v) perfluorooctylbromide (perflubron,;PFOB), on porcine and human platelet activation and function. We measured both (1) stimulated ex-vivo porcine platelet aggregation pre and post infusion of either perflubron or control (vehicle only) emulsions and (2) stimulated in vitro human platelet calcium flux in the presence of perflubron emulsion or control emulsions. Platelet aggregation stimulated by collagen, ADP or arachadonic acid (AA) was inhibited in ex-vivo porcine platelets following infusion of perflubron emulsion at a dose of 3 ml/kg (0.2 ml/kg/min). Inhibition was dose-dependent and was decreased when the dose of perflubron emulsion was reduced to 1.0 or 0.3 ml/kg. Infusion of saline or "vehicle" emulsions had little or no effect on stimulated ex-vivo pig platelet aggregation. Fluosol infusion was associated with inconsistant inhibition of platelet aggregation. A23187- or AA-stimulated calcium flux of human platelets in vitro was inhibited in the presence of 1% (v/v) perflubron emulsion. Similar effects were seen with Fluosol, or Intralipid. This inhibition was agonist dose-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Diphosphate↗
Immediate, bilateral transverse rectus abdominis musculocutaneous (TRAM) flap reconstruction after mastectomy.
Although breast reconstruction has been shown to provide psychological benefits in mastectomy patients, there is reluctance to perform immediate, bilateral TRAM flap reconstruction because of concerns regarding magnitude of the procedure, length of hospitalization, potential complications, and long-term recovery. Between June, 1990 and March 1992, 15 patients underwent immediate, bilateral TRAM flap reconstruction following bilateral mastectomy at the University of Michigan Hospitals. Diagnoses included lobular carcinoma in situ (nine patients), strong family history of breast cancer (five), or bilateral breast cancer (one). Invasive breast cancer was present in three patients. Three modified radical mastectomies and 27 simple mastectomies were performed. Bilateral pedicle TRAM flap reconstruction was carried out at the same time in all patients (30 flaps total). Marginal loss occurred in one flap (3%). Additional complications included marginal necrosis of the abdominal donor site wound (one), wound infection (two), and abdominal donor site hernia (one). Median hospital stay was 7 days. Median follow-up was 13 months (range 4-25 months). All patients have resumed their accustomed pre-operative activity patterns. These findings demonstrate that immediate, bilateral TRAM flap reconstruction is a safe and effective option for breast reconstruction after mastectomy.
Abdominal Muscles↗
Identification of xanthine oxidase activity following reperfusion in human tissue.
In this series of experiments, we surveyed xanthine oxidase activity after microvascular transfer in the venous effluent after reperfusion of human rectus abdominis muscle (n = 8) and jejunum (n = 4). Enzyme activity was correlated with duration of ischemia and biochemical markers of cellular injury. Xanthine oxidase (XO) activity was measured spectrofluorometrically using a pterin assay, whereas cellular injury was measured with commercial creatinine phosphokinase activity assay and lipid peroxidation products using a spectrophotometer. The data demonstrated that XO activity was statistically significantly increased in muscle flaps kept at room temperature during ischemia compared with muscle flaps that were cooled (p < 0.05). Creatinine phosphokinase activity was also increased after 15 minutes of reperfusion in muscle flaps that were not cooled (p < 0.05). Two of the jejunal free flaps had ischemia times of > 1 hour and had elevated XO activity after reperfusion despite cooling (p < 0.05). Two other jejunal flaps had ischemia times of < 1 hour, but in one case, the XO activity was increased before harvest. The other case had no increase in XO activity.
Abdominal Muscles↗
Control of hemorrhage during renal failure with triglycyl-lysine-vasopressin.
A 35-year-old man with chronic renal failure developed toxic epidermal necrolysis due to combination antibiotic therapy for a community acquired pneumonia. During wound care for his toxic epidermal necrolysis, he developed massive bleeding, a 4 to 6 unit blood loss at each dressing change, due to uremia-associated platelet dysfunction and thrombocytopenia. After failure of standard therapy, the man was treated with intravenous triglycyl-lysine-vasopressin, a selective peripheral vasoconstrictor. Transfusion requirements stopped during treatment. This man went on to full recovery with complete wound healing. Triglycyl-lysine-vasopressin effectively reduced skin blood loss in this man with toxic epidermal necrolysis and an intrinsic hemostatic defect, and may be useful in other patients with cutaneous blood loss.
Adult↗