Effective immunity to dental caries: passive transfer to rats to antibodies to Streptococcus mutans elicits protection

Rat dams, given intravenous injections of heat-killed Streptococcus mutans 6715, mutant C211 demonstrated significant agglutinin activity to the homologous S. mutans in colostrum, milk, and serum. This antibody activity was associated with the immunoglobulin G (IgG) class. High titers of anti-S. mutans antibody associated with the IgG class were also exhibited in the sera and saliva of the offspring that suckled these dams. After challenge with the homologous, live S. mutans, these offspring developed significantly fewer caries on all molar surfaces than did nonimmunized infected controls. A secretory immune response (manifested by the presence of specific IgA antibody to S. mutans in colostrum and milk) was elicited (i) in rat dams locally injected, in the region of the mammary gland, with heat-killed S. mutans antigen, and (ii) in other rat dams that were provided formalin-killed S. mutans in their drinking water. Offspring suckling these dams were challenged with virulent S. mutans before weaning and developed significantly fewer caries than did their infected controls. These findings clearly suggest that passively derived IgG or IgA antibodies to S. mutans are protective against dental caries.     

The effect of antibody to Streptococcus mutans in saliva on caries activity and S. mutans adhering

An indirect enzyme-linked immunosorbent assay (ELISA) was used for measuring IgA antibody to whole cell of Streptococcus mutans (serotype c) in saliva. 36 parotid salivary samples of human were collected from two groups: Caries free (CF) and caries sensitive (CS). The result shows that the IgA antibody to S. mutans in CF group was higher than those in CS group (P < 0.05). The saliva antibody was gained from the rabbits by injection with S. mutans (serotype c), and the adhesion of S. mutans--3H on the surface of hydroxylapatite beads treated by rabbit's saliva was measured. The results show that the saliva with immunity could inhibit the S. mutans to adhere on the HA beads (P < 0.05). It means saliva antibody may prevent caries through inhibition of S. mutans from adhesion.     

A comparison of antibody responses to veterinary vaccine antigens potentiated by different adjuvants

Six adjuvant formulations were compared for their ability to potentiate the primary and memory antibody responses in mice to three companion animal vaccine immunogens--feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), and a recombinantly-derived heartworm antigen. The combination of a novel bacterial immunostimulator, gliding bacterial adjuvant (GBA), either adsorbed onto an aluminum hydroxide gel (Rehydragel HPA), or emulsified with a vehicle of polyalcohol and detergent, elicited the strongest memory responses to both virus preparations. Both forms of aluminum hydroxide gels administered without GBA gave similar levels of adjuvant effects, on par with or greater than those generated by incomplete Freund's adjuvant (IFA). The Acemannan immunostimulant was not effective in increasing the responses to the virus antigens, but increased the primary response to the heart-worm antigen over tenfold from control levels. All preparations appeared to be well tolerated, with no detectable adverse reactions observed in any of the 250 mice used. The proven safety of aluminum hydroxide adjuvants and the apparent absence of adverse reactions seen with GBA make this vehicle/adjuvant formulation worthy of additional study.     

Humoral immunity to commensal oral bacteria in human infants: salivary antibodies reactive with Actinomyces naeslundii genospecies 1 and 2 during colonization

The secretory immune response in saliva to colonization by Actinomyces naeslundii genospecies 1 and 2 was studied in 10 human infants from birth to 2 years of age. Actinomyces species were not recovered from the mouths of the infants until approximately 4 months after the eruption of teeth. However, low levels of secretory immunoglobulin A1 (SIgA1) and SIgA2 antibodies reactive with whole cells of A. naeslundii genospecies 1 and 2 were detected within the first month after birth. Although there was a fivefold increase in the concentration of SIgA between birth and age 2 years, there were no differences between the concentrations of SIgA1 and SIgA2 antibodies reactive with A. naeslundii genospecies 1 and 2 over this period. When the concentrations of SIgA1 and SIgA2 antibodies reactive with whole cells of A. naeslundii genospecies 1 and 2 were normalized to the concentrations of SIgA1 and SIgA2 in saliva, the A. naeslundii genospecies 1- and 2-reactive SIgA1 and SIgA2 antibodies showed a significant decrease from birth to 2 years of age. The fine specificities of A. naeslundii genospecies 1- and 2-reactive SIgA1 and SIgA2 antibodies were examined by Western blotting of envelope proteins. Similarities in the molecular masses of proteins recognized by SIgA1 and SIgA2 antibodies, both within and between subjects over time, were examined by cluster analysis and showed considerable variability. Taken overall, our data suggest that among the mechanisms Actinomyces species employ to persist in the oral cavity are the induction of a limited immune response and clonal replacement with strains differing in their antigen profiles.     

Detecting approximal dental caries with transillumination: a clinical evaluation

Independent examinations of 300 patients were conducted to evaluate fiber optic transillumination's performance in caries detection. FOTI was used as an adjunct to clinical and radiographic examinations for caries, restoration or secondary caries of approximal surfaces in maxillary anterior permanent teeth. Clinical and radiographic examinations were significantly more effective.     

Control of mucin molecular forms expression by salivary protease: differences with caries

1. A protease activity capable of degradation of the high mol. wt salivary mucus glycoprotein to a low mol. wt glycoprotein form was identified in human submandibular gland secretion. 2. The protease exhibited optimum activity at pH 7.0-7.4, and gave on SDS-PAGE under reducing conditions two major protein bands of 48 and 53 kDa. The enzyme showed susceptibility to PMSF, alpha 1antitrypsin, and egg white and soybean inhibitors, a characteristic typical to serine proteases. 3. The activity of the protease towards the high mol. wt mucus glycoprotein was found to be 3.8-fold higher in submandibular gland secretion of caries-resistant individuals than that of caries-susceptible. Furthermore, the enzyme from both groups displayed greater activity against the mucus glycoprotein of caries-resistant subjects. 4. Since the low mol. wt salivary mucus glycoprotein form is more efficient in bacterial clearance than the high mol. wt mucin, the enhanced expression of this indigenous salivary protease activity towards mucin may be the determining factor in the resistance to caries.     

The relationship of dental calculus to caries, gingivitis, and selected salivary factors in 11- to 13-year-old children in Chiang Mai, Thailand

Thai children have been shown to accumulate large amounts of dental calculus. The purpose of this study was to examine the relationship of calculus to caries and gingivitis, and salivary conditions which may contribute to calculus accumulation. Four-hundred and thirty-nine (439) children from 18 schools in Chiang Mai were selected for this study. The children were given oral examinations to determine calculus index (CI); decayed, missing, and filled surfaces (DMFS); decayed, missing, and filled teeth (DMFT); gingival index (GI); and plaque index (PI). Children with mean CI scores > or =1 (206) were assigned to the calculus group; the 233 children with mean CI scores of <1 to the noncalculus group. Saliva was collected from 60 randomly-selected children in each group. Unstimulated and stimulated whole saliva and stimulated parotid saliva were assessed for flow rate, pH, and buffer capacity using 2 methods. Results showed that calculus status was not significantly associated with caries, but that there was a high association between gingivitis and plaque status with calculus accumulation (P < 0.001). There were no significant differences in saliva flow rate, pH, or buffer capacity between calculus and noncalculus groups. The lack of association between calculus status and caries indicated these 2 conditions have different etiologies and suggests the importance of plaque and calculus prevention programs, in addition to caries control efforts, to maintain oral health of Thai children.     

Iontophoresis: an alternative in the treatment of dental caries?

Celiac sprue (CS) is frequently complicated by malignancy, most commonly small intestinal lymphoma. Our study was performed in an area with a high prevalence of CS to define the clinical features, response to treatment, and outcome of this tumor. Of a total of 31 lymphomas complicating CS identified, 30 case records and 24 tumor specimens were reviewed. Overall 1-year survival was 9 of 29 (31%) and 5-year survival 3 of 27 (11%). Seven previously diagnosed celiac patients developed lymphoma; length on gluten-free diet ranged from 12 to 252 months (median 44 months). In this group, presentation was nonspecific, diagnosis difficult, and survival poor (lymphoma diagnosed in life in four of seven, mean survival 2.25 months). Twenty-three patients had CS and lymphoma diagnosed during the same illness. In this group, 14 of 23 presented with a surgical emergency and were treated with tumor resection and chemotherapy. Nine are disease-free and alive or died of another cause after 10-196 months (mean 74 follow-up). Celiac-associated lymphoma is a frequent, difficult to diagnose, and commonly fatal complication of CS. An aggressive diagnostic approach, including laparoscopy, is recommended. Long-term survival can be expected in a significant number of these patients and in our series was almost exclusively confined to those treated with chemotherapy.     

Effective treatment of cobalamin deficiency with oral cobalamin

Because cobalamin deficiency is routinely treated with parenteral cobalamin, we investigated the efficacy of oral therapy. We randomly assigned 38 newly diagnosed cobalamin deficient patients to receive cyanocobalamin as either 1 mg intramuscularly on days 1, 3, 7, 10, 14, 21, 30, 60, and 90 or 2 mg orally on a daily basis for 120 days. Therapeutic effectiveness was evaluated by measuring hematologic and neurologic improvement and changes in serum levels of cobalamin (normal, 200 to 900 pg/mL) methylmalonic acid (normal, 73 to 271 nmol/L), and homocysteine (normal, 5.1 to 13.9 micromol/L). Five patients were subsequently found to have folate deficiency, which left 18 evaluable patients in the oral group and 15 in the parenteral group. Correction of hematologic and neurologic abnormalities was prompt and indistinguishable between the 2 groups. The mean pretreatment values for serum cobalamin, methylmalonic acid, and homocysteine were, respectively, 93 pg/mL, 3,850 nmol/L, and 37. 2 micromol/L in the oral group and 95 pg/mL, 3,630 nmol/L, and 40.0 micromol/L in the parenteral therapy group. After 4 months of therapy, the respective mean values were 1,005 pg/mL, 169 nmol/L, and 10.6 micromol/L in the oral group and 325 pg/mL, 265 nmol/L, and 12.2 micromol/L in the parenteral group. The higher serum cobalamin and lower serum methylmalonic acid levels at 4 months posttreatment in the oral group versus the parenteral group were significant, with P < .0005 and P < .05, respectively. In cobalamin deficiency, 2 mg of cyanocobalamin administered orally on a daily basis was as effective as 1 mg administered intramuscularly on a monthly basis and may be superior.     

Assessment of the caries activity test (Cariostat) based on the infection levels of mutans streptococci and lactobacilli in 2- to 13-year-old children's dental plaque

It is generally agreed that mutans streptococci and lactobacilli are associated etiologically with dental caries. The caries activity test, Cariostat, was designed to measure the pH decrease caused by microorganisms in the plaque sample obtained from the buccal surfaces. Researchers found the test to be a reliable, diagnostic, and predictive device. Incubation was done on MS and MSB plates in an atmosphere of 95 percent N and 5 percent CO at 37 degrees C and for 48 hours. The relationship of the Cariostat scores and the pH values are shown in a table. The test scores are shown for two age-groups: Ages two-to-six years with primary dentitions, and ages five-to-thirteen years with mixed dentitions. The advantages of the Cariostat test are: the sampling method is simple and the time of analysis is short; the test can be used for the very young and for patients difficult to manage; and it requires no specialized knowledge or equipment.     

Cardiac allograft vasculopathy: IgM antibody responses to donor-specific vascular endothelium

Stunning and slaughter trials were conducted to evaluate the influence of carcass orientation (inverted or supine), angle of feather extraction (parallel or perpendicular to the carcass surface), and slaughter method (exsanguination without or with spinal cord transection) on feather retention force (FRF) in commercial broilers sampled ante-, peri-, and post-mortem. The pectoral, sternal, and femoral feather tracts were sampled before and after stunning contralaterally, with a maximum indicating force gauge, from broilers suspended on a shackle (inverted) or laying on a table (supine). For all trials and sample periods FRF was consistently greater in the femoral area (547 to 679 g) than in the pectoral area (273 to 391 g), with the sternal feather tract requiring the least force at 246 to 343 g. Feathers extracted parallel to the carcass resulted in consistently greater FRF (9 to 29%) than feathers extracted at a perpendicular angle, at all sample periods. Broilers suspended on shackles ante- and peri-mortem had higher FRF values (5 to 30%) than those restrained in shackles in a supine position on a table. Other parameters resulted in minor and inconsistent alterations in FRF. Electrical stunning, when not followed by bleeding, resulted in small reductions in FRF (up to 7%). Bleeding after stunning without or with spinal cord transection resulted in variable peri-mortem FRF changes (+7 to -11% and +11 to -11%, respectively). Only in the pectoral feather tract was there a significant increase (5 to 6%) in FRF as broilers went from the ante- to peri-mortem state. At 2 and 6 min after stunning and initiation of exsanguination, post-mortem FRF was unaffected by carcass orientation for the pectoral and femoral tracts.     

The hemagglutination inhibition antibody responses to an inactivated influenza vaccine among healthy adults: with special reference to the prevaccination antibody and its interaction with age

The immunogenicity of the trivalent split-virus influenza vaccine was investigated among 70 healthy adults (mean age: 48.5, range: 36-68). The vaccine antigens were: A/Yamagata/32/89 (H1N1); A/Beijing/352/89 (H3N2); and B/Bangkok/163/90. Regarding the entire sample, the vaccine induced a tenfold or more rise on the average in the hemagglutination inhibition (HAI) antibody to each antigen. The response rates (greater than or equal to a fourfold rise) were about 90% or more among those with a prevaccination titer < or = 1:64 (equivalent to < or = 1:16 on the Western scale; in Japan, the HAI titers are expressed by the final, and not the initial, dilution of the serum; from hereon our findings will be expressed using the Japanese scale), whereas they were 0-50% at > or = 1:128. Thus, the prevaccination titer was negatively associated with antibody induction. The achievement rates (postvaccination titer > or = 1:128) among those with a prevaccination titer < 1:16 remained at 48-68%. Regarding the analysis of variance, a significant effect on antibody induction was indicated for the prevaccination titer (P < or = 0.002), but not for age (P > or = 0.425). The interaction between the prevaccination titer and age was significant for A/Yamagata (P = 0.030), while it was also suggestive for A/Beijing (P = 0.054): as age increased, those with no preexisting antibody (< 1:16) showed greater titer rises, in contrast to the smaller rises among those with a titer > or = 1:16. Based on the attack survey conducted separately, the vaccine efficacy on influenza-like illnesses with fever < or = 37 degrees C and > or = 37.5 degrees C was calculated to be 16% (95% confidence interval: -66% to 57%) and 37% (-55% to 74%), respectively.     

Effect of Cervitec varnish on the salivary Streptococcus mutans levels in the patients with fixed orthodontic appliances

The aim of the present study was to assess the efficiency of a 1% chlorhexidine-containing varnish (Cervitec, Vivadent, Liechtenstein) on the levels of Streptococcus mutans in saliva of patients with fixed orthodontic appliances using the Dentocult-SM (Vivadent, Liechtenstein) technique for the microbiological investigation. Eighty subjects participated in the study and, divided randomly into two equal groups in which one group was treated with the placebo varnish (Vivadent, Liechtenstein) for negative controls. Streptococcus mutans in saliva of the subject was sampled and enumerated by using the Dentocult-SM dip-slide technique for periods of one, two four and twelve weeks after a single varnish application. The results were evaluated statistically. After the chlorhexidine containing varnish treatment the levels of Streptococcus mutans in saliva were significantly reduced after one week (p < 0.01) and continued reduction for one month (p < 0.05). After twelve weeks Streptococcus mutans levels in saliva were given a relative increase. No significant suppression was found in the placebo group (p > 0.05). The results suggested that Cervitec varnish reduces salivary Streptococcus mutans levels and that the application should be repeated every 3 months to get antibacterial effect.     

Immunological responses from non-exposed donors to malaria antigens: implications for immunity and pathology

An approach to identification of epitopes suitable for vaccine development has been to locate regions of malaria target antigens that are recognized by individuals with clinical immunity. This has applied to identification of T- and B-cell epitopes. It is now realized, however, that T cells from individuals without prior exposure to malaria can respond to malaria parasites, malaria proteins, and peptides copying protein sequences. Such observations raise questions about which epitopes we should be targeting for vaccine development, but also challenge our understanding of immunological memory. Such responses from non-exposed individuals may also be important in expression of disease symptoms.     

CpG-containing synthetic oligonucleotides promote B and cytotoxic T cell responses to protein antigen: a new class of vaccine adjuvants

Foreign DNA has been shown to impinge on immune cell function by an as yet unidentified mechanism. We and others have demonstrated that single-stranded (ss) DNA containing the motif CpG flanked by two 5' purines and two 3' pyrimidines are mitogenic for B cells and activate macrophages to release tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-6 or IL-12. Because of these pro-inflammatory responses we investigated if ssDNA would serve as a potential vaccine adjuvant. Here we show that CpG-containing oligonucleotides represent a powerful adjuvant for both humoral and cellular immune responses. When ssDNA was incorporated into inocula, specific antibody titers of the IgG2 isotype were enhanced by greater than 100-fold. Primary cytotoxic T lymphocyte responses generated to either unprocessed protein antigen or major histocompatibility complex class I-restricted peptide were exceedingly strong. Evidence is also provided that oligomers directly influenced T cell receptor-triggered T cell proliferation. Thus ssDNA oligomers may serve as inexpensive and safe vaccine adjuvants and, in addition, differential effects due to sequence may allow for directed responses.     

Effect of long-term therapies with penicillin and sulfadiazine on Streptococcus mutans and lactobaccilli in dental plaque

Plaque samples were obtained from 13 children receiving long-term therapy with benzathine penicillin for the prevention of rheumatic fever recurrences, 31 children receiving oral sulfadiazine for the same purpose, and 29 untreated siblings. The therapies were found to have no effect upon the proportions of Streptococcus mutans or lactobacilli in dental plaque, upon the percentage of children harboring the organisms, nor upon the susceptibility of the organisms to penicillin and sulfadiazine. Of the S. mutans strains tested, 97% had a minimal inhibitory concentration of penicillin G of less than 48 ng/ml and, of the lactobacillus strains tested, 96.8% had a minimal inhibitory concentration of less than 1,600 ng/ml. All strains of both organisms were profoundly resistant to sulfadiazine.     

Adverse impact of infections on antibody responses to measles vaccination

Allelic frequencies for up to five short tandem repeat systems (HumTH01. HumVWA, HumF13B, HumCD4, HumD2111) were analyzed in seven population samples from Asia using the polymerase chain reaction and gel electrophoresis. No deviations from Hardy-Weinberg equilibrium were observed. Two new alleles of the CD4 and TH01 loci were detected, and sequenced and their molecular structure is presented. A phylogenetic tree based on Thai, Han Chinese (from the northeast of China), Japanese, German and Ovambo allelic frequencies was constructed and demonstrates the close relationship of the Asian populations. Additionally, allelic frequency data for the VWA and TH01 systems were determined for the south Chinese minorities Bai, Dai and Qiang and for Koreans and compared with the above data. The Bai and Dai populations were clear outliers of the cluster of all other Asians, indicating an unexpected pattern of genetic heterogeneity of the Chinese nation. Two clusters of Asian populations could be established: the Koreans and Japanese together with the Han and Qiang Chinese, and, forming a separate cluster, the Bai and Dai populations.