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Biomedical subjects

D Engel

Publications and source records attributed to D Engel.

At least 37 records · Page 2Linked to original sources

Serum immunoglobulin G antibody to Porphyromonas gingivalis in rapidly progressive periodontitis: titer, avidity, and subclass distribution.

Porphyromonas gingivalis is a suspected pathogen in rapidly progressive periodontitis (RPP). We have determined the anti-P. gingivalis serum immunoglobulin G (IgG) isotype response and avidity and the subclass titer distributions for 30 RPP patients and 30 age-, sex-, and race-matched healthy subjects by using enzyme-linked immunosorbent assay technology. Patients and control subjects were classified as seropositive if their total IgG response to P. gingivalis was twofold or more than the median response in healthy subjects. The predominant antibody responses for both patients and healthy subjects were IgG2 and IgG3, with a subclass order of IgG2 greater than IgG3 greater than IgG1 greater than IgG4. The avidity of the IgG response was highest for the seropositive healthy subjects and was no different between seronegative and seropositive RPP patients. The subclass antibody responses did not depend on gender, and there were no correlations between titer, avidity, or subclass with disease severity in the RPP patients as measured by pocket depth or bone loss on dental X rays. The seronegative RPP patients exhibited antibody responses that were greater than the responses of seronegative healthy subjects for all four subclasses, while the seropositive RPP patients had higher IgG1 and IgG4 levels than seropositive healthy subjects. These findings are consistent with the hypothesis that both carbohydrate and protein antigens are important in the IgG response to P. gingivalis. The relative predominance of IgG2, a subclass which lacks strong complement fixation and opsonic properties, and the low avidity of patient anti-P. gingivalis IgG antibodies suggest that humoral responsiveness to infection with P. gingivalis may be ineffective in clearing this organism.

Adolescent

[AIDS counseling in social welfare for prostitutes in the rural area].

Prostitute welfare and AIDS counselling are in the hands of one person in the rural area of the Westerland district. This offers the opportunity of continuously preventing this disease and giving guidance and the "human touch" in close care in case of a possible infection, especially in view of the lower number of cases examined and advised compared with the figures in the big cities. An anonymous poll among 41 prostitutes shows that they approve of and are satisfied with the concept of the "G-welfare". It also shows that the prostitutes themselves are hardly aware of the HIV-risk, that their customers only rarely accept condoms and that there are problems in the use and the toleration of condoms. These difficulties are the main aspects of the preventive work, as well as the psycho-social care and the personal relationship to those examining.

Acquired Immunodeficiency Syndrome

Altered lymphocyte populations in sphha/sphha mice with chronic hemolytic anemia.

Lymphocyte kinetics and phenotype were examined in mutant anemic sphha/sphha mice that manifest a lifelong lymphocytosis which accompanies their chronic hemolytic anemia. Anemic mice have significant increases in CD4+, CD8+, and sIgM+ lymphocytes in peripheral blood. Pulse and continuous infusion studies with [3H]TdR suggest that this apparent lymphoid expansion is not due to increased production of lymphocytes in bone marrow or thymus but rather to a redistribution of lymphocytes from the spleen to other peripheral lymphoid tissue sites as well as increased proliferation of T and B lymphocytes in lymph nodes. This murine model could be useful to examine lymphocyte perturbations that may accompany chronic hemolytic anemia in humans.

Anemia, Hemolytic, Congenital

Humoral immune responses to Porphyromonas gingivalis before and following therapy in rapidly progressive periodontitis patients.

We have performed studies aimed at elucidating the nature of the humoral immune response in rapidly progressive periodontitis (RPP). We analyzed the sera of 36 periodontally normal subjects and 36 RPP patients for titers and avidities of IgG antibodies reactive with the antigens of Porphyromonas gingivalis using ELISA, prior to and following treatment. We used whole-cell sonicate, purified lipopolysaccharide (LPS), and total extractable protein as plate antigens. Twelve of the patients had antibody titers at least 2-fold greater than the median of the controls and were designated as seropositive. The remaining 24 patients had titers that did not exceed twice the median titer of the controls and were designated as seronegative. For both patient groups, antibody titers were highest when whole-cell antigen was used, intermediate for LPS, and lowest for the protein fraction. Following treatment, median titer for seropositive patients decreased from pretreatment values of 241.7 to 76.5, while median titer for seronegative patients increased from 39.5 to 80.1. Avidities of pretreatment sera from both patient groups for all 3 antigen preparations were lower than the median avidities of the control sera. Avidity significantly increased following treatment to levels greater than those for control sera in both patient groups. Thus, some young adults with severe periodontitis mount a humoral immune response and produce high levels of serum IgG antibodies reactive with antigens of P. gingivalis, while others do not. The antibodies produced are of relatively low avidity, and may therefore be relatively ineffective biologically. Therapy, which greatly reduces antigen load, appears to stimulate production of higher avidity IgG antibodies in both patient groups; in the seropositive group, low avidity antibodies appear to be replaced by antibodies of higher avidity. Both the purified LPS and protein fractions contain reactive antigen(s), although LPS binds more antibody. Our data are consistent with the idea that many RPP patients do not produce protective levels of biologically functional antibody during the course of their natural infection, but they may be stimulated to do so by treatment.

Adult

Transplantation studies in mice with congenital hemolytic anemia.

Sphha/sphha anemic mice have an abnormality in the erythroid membrane protein, alpha spectrin, and exhibit multiple related clinical abnormalities, including spherocytosis, shortened red cell survival, chronic hemolysis, hemosiderosis, and extramedullary hematopoiesis. In addition, these mutant mice exhibit a granulocytosis and lymphocytosis, lymph node hyperplasia, elevated serum immunoglobulins, membranoproliferative glomerulonephritis, and decreased lifespan--abnormalities that are less clearly attributable to a spectrin defect. In order to further elucidate the mechanisms of disease in these animals, we undertook a series of bone marrow transplantation experiments. Transplantation of anemic marrow into lethally irradiated congenic +/+ mice resulted in chronic spherocytosis, hemolytic anemia, peripheral leukocytosis, and extramedullary hematopoiesis. Additionally, transplant recipients of anemic marrow which had received a higher radiation dose (12 Gy) had increased numbers of peripheral blood CD4+ and CD8+ lymphocytes, a hypocellcular thymus, and a severe pneumonitis characterized by nodular areas of consolidation and edema. Mice receiving congenic +/+ marrow and irradiated with the same radiation dose exhibited minimal pulmonary abnormalities. Anemic mice transplanted with congenic +/+ marrow usually died, but the survivors exhibited reversal of some clinicopathological changes. These results would suggest that the clinical abnormalities of sphha/sphha mice are in part attributable to abnormalities of hematopoietic stem cells but may also involve defects in other cell types. The pathogenesis of the accompanying lymphoid abnormalities observed in this mutant anemic mouse and any correlation with the erythroid spectrin defect are presently unknown. The pulmonary disease that develops in the transplant recipients of anemic marrow needs to be characterized further but may represent a unique model of lung injury.

Anemia, Hemolytic, Congenital

Bacterial luminescence: a new tool for investigating the effects of acoustic energy and cavitation.

An assay utilizing luminescent bacteria, Photobacterium phosphoreum, was adapted to assess the antibacterial effects of acoustic energy. Acoustic pressures up to 67 kPa in the 100- to 800-Hz frequency range were applied to bacteria freely suspended in a liquid medium. Bacterial luminescence decreased after sonication, thus showing sensitivity to the effects of acoustic energy. This decreased luminescence was linearly related to exposure duration, appeared independent of acoustic frequency in this range, and was significantly heightened by the presence of cavitation. High-frequency components of the acoustic emission were recorded from the sonicated fluid, and it was found that the decrease in luminescence due to sonication was directly related to the logarithm of the acoustic emission. Viability studies on exposed bacteria indicated a diminution of luminescence without bacterial death. The potential use of luminescent bacteria in assessing the biological effects of acoustic energy-generating systems is discussed.

Acoustics

Oral mucosal lesions: association with the presence of antibodies to the human immunodeficiency virus.

To assess the relationship between oral lesions and antibodies to the human immunodeficiency virus, oral examinations of 803 homosexual males were conducted at the time of serologic testing. Nineteen percent were HIV seropositive. Thirty percent of antibody-positive subjects had one or more oral lesion(s), as compared with 7% of antibody-negative subjects (p less than 0.001). The presence of oral lesions was significantly associated with HIV seropositivity: a subject was 5.7 times as likely to have serum antibodies if he had one or more oral lesions (95% confidence interval, 3.5 to 9.1; p less than 0.001). This significant association with HIV seropositivity was only partially explained by cigarette smoking (adjusted odds ratio 3.1; 1.4-6.8; less than 0.006). Specific conditions that were significantly associated with seropositivity included candidiasis, hairy leukoplakia, periodontal disease, and Kaposi's sarcoma. Other diseases identified included acute necrotizing ulcerative gingivitis, mucocutaneous ulcerations, and oral warts. Oral findings may occur earlier in the natural history of infection than previously reported.

Adult

Polyclonal B-cell activation in periodontitis.

The evidence that periodontitis-associated bacteria contain potent PBA factors is very strong. Clearly, antibodies directed against non-oral antigens are produced in the inflamed periodontal lesion, and PBA appears to contribute to that production. It is also clear that B cells and plasma cells are the major cell types in the periodontal lesion. Furthermore, alterations in the regulation of B-cell responses to PBA factors are associated with severe periodontal disease. However, evidence demonstrating that activated B cells and plasma cells are directly involved in the pathogenic mechanisms leading to destruction of the periodontal support is still circumstantial. Polyclonal B-cell activation and potential pathways by which PBA-stimulated cells could be involved in periodontal destruction remain largely hypothetical. It appears that IL-1 is an important osteoclast-activating agent, and that LPS, which is a potent PBA factor in many systems, can elicit IL-1 production by B cells as well as by the monocyte/macrophage lineage. Recent data indicating that IL-1 is produced by numerous malignant B-cell lines lend support for the idea that B-cell IL-1 could be important in bone resorption. It is also likely that polyclonal activation may lead to production of autoantibody such as anti-type I and anti-type III collagens, and the destruction of self tissues through ADCC reactions, immune complex formation, and complement activation. Further research is needed to determine how the B cell/plasma cell may participate in tissue injury in periodontitis, and how the B-cell response to PBA factors is regulated.

Animals

Epidemiology of acute necrotizing ulcerative gingivitis.

In the last 60 years, there have been approximately 50 studies of various suspected risk factors associated with acute necrotizing ulcerative gingivitis. Two thirds of these studies have been either surveys or case reports; nearly all the rest have been case-control studies. There have been only a few longitudinal and population-based studies, most of which were in high-risk populations. The findings of many studies pertain to gingivitis in general rather than in acute necrotizing ulcerative gingivitis in particular; the findings of other studies are based on small numbers or solely on case histories without the inclusion of control subjects. There are comparisons between the epidemiology of acute necrotizing ulcerative gingivitis as it occurs in military populations and the epidemiology of meningococcal meningitis (98-103). Both diseases have been reported in closed communities such as in young recruits away from home and in new surroundings. A temporal trend upward in disease frequency was described for both infections during World War II. Both infections appear to be characterized by low communicability, with no documented transmission by fomites or vectors. Furthermore, active disease in both cases is associated with markedly increased numbers of normally indigenous flora: B. intermedius in the case of acute necrotizing ulcerative gingivitis and Neisseria meningococcus in the case of epidemic meningococcal meningitis. Risk factors associated with both diseases include crowding, physical fatigue, increased stress, low socioeconomic status, and failure of host defense mechanisms. In general, there is potential for longitudinal studies of young people such as new military recruits and college students who are undergoing the transition from dependence to independence. It is intriguing that these young adults are suddenly at increased risk of this disease in late adolescence when they should be at peak fitness and, just as suddenly, at decreased risk after their early thirties. It appears that the dynamic tension between bacterial agents, environmental stressors, and host defense mechanisms is abruptly altered in certain young people, allowing the characteristic lesions to develop. Furthermore it appears that, in the United States at least, the disruption is limited primarily to white people relative to black people. It is possible that disease develops because young adults are brought together from diverse locations and perhaps exposed to a new microbial agent. However, acute necrotizing ulcerative gingivitis has not been demonstrated clearly to be transmissible, and if it is, the mode of transmission is not known.(ABSTRACT TRUNCATED AT 400 WORDS)

Female

Clinicopathologic features of young and old sphha/sphha mice. Mutants with congenital hemolytic anemia.

A colony of mice with congenital hemolytic anemia, sphha/sphha, were evaluated over a 3-year period. Prominent findings included decreased survivability, reticulocytosis, increased peripheral blood leukocytes, extramedullary hematopoiesis in liver and spleen, lymphoid hyperplasia and membranoproliferative glomerulonephritis. Older (12 to 21 months) anemic animals had elevated serum levels of IgG1 and IgA. There was deposition of C3, IgG, IgM, and IgA in renal glomeruli of both control and anemic mice, but deposition of IgM and IgA was more prominent and widely distributed in anemic animals and correlated with mesangial expansion and the presence of electron dense deposits in the mesangium and in glomerular capillary walls. Prominent renal tubular hemosiderosis was noted in young and old anemic mice. The relation between the hemolytic anemia and glomerular disease is unclear but these mice may be an animal model useful for exploration of changes attendant with chronic hemolysis and evaluation of renal disease that accompanies hemolytic anemia.

Age Factors

Deionization of formamide with Biorad AG501-X(D).

We have studied different conditions of the deionization of formamide with Biorad mixed bed resin AG501-X(D) and find that contrary to the popular usage, drying the resin before deionization produces the best results. In a typical deionization procedure, conductivity initially goes down, reaches a minimum plateau and finally goes up again. The initial rate of deionization, the minimum conductivity reached at the plateau and the rate of final rise in conductivity depend on whether the resin is dry or wet (i.e., straight from the bottle) and on the amount of resin used. In general, wet resin produced faster initial deionization, higher minimum conductivity and quicker final rise in conductivity. Surprisingly, a smaller amount (5%) of resin worked better than a larger amount (20%). With smaller amount of resin, although initial deionization was slower, the minimum conductivity achieved was lower and the final rise in conductivity was slower. This was partly due to the fact that the conductivity of formamide increases faster with increasing amount of water in it.

Chromatography, Ion Exchange

Simultaneous cell cycle analysis and two-color surface immunofluorescence using 7-amino-actinomycin D and single laser excitation: applications to study of cell activation and the cell cycle of murine Ly-1 B cells.

The DNA-binding, fluorescent dye 7-amino-actinomycin D (7AAD) is efficiently excited by the 488 nm laser line commonly used in flow cytometry, but yields fluorescence emission further into the red spectrum than alternative DNA-specific fluorochromes. In this report, we show that the spectral properties of 7AAD allow single-laser analysis of DNA content and cell cycle simultaneously with two cell surface markers labeled with fluorescein (green)-and phycoerythrin (orange)-conjugated antibodies. The use of 7AAD makes three-color analysis practical and feasible, using the most widely available flow cytometric instruments. The power of this technique was demonstrated in two systems. Staining of human peripheral blood lymphocytes (PBL) with 7AAD was demonstrated to be dependent on cell activation and chromatin conformation; PHA-stimulated cells which have become activated and express IL 2 receptors had greater 7AAD fluorescence than nonactivated, IL 2 receptor-negative cells. Cell cycle analysis of mouse splenocytes stained with fluorescent antibodies to IgM and to Ly-1 demonstrated that the proportion of S and G2 phase cells in native spleen varies strongly among the subsets of cells identified with these markers. Of particular interest was the striking finding that the Ly-1+/IgM+ subset (Ly-1 B cells) is greatly enriched for cells in the S phase fraction. This is important because Ly-1 B cells have been associated with the production of autoantibodies, and is consistent with reports that these cells have a lymphoblastoid or a plasmablast morphology. We hypothesize that Ly-1 B cells may belong to a subset of in vivo activated cells which are either rapidly proliferating or are arrested in S phase.

Animals

Can juvenile scoliosis be corrected by circumscribed radium-irradiation of the spine?

In 1936 scoliosis was produced in growing animals by exposing one side of one or more vertebrae to radium action. The purpose of this treatment was to recurve existing curvatures of the spine on the same principle. No attempt has been made so far to correct congenital scoliosis of infants by this method. Hundreds of infants treated by X-ray for Wilms' tumor developed incidental spinal curvatures. In none of these cases was there any recorded mention of damage to the spinal cord or any other organ. Since the epiphyseal plate is much more sensitive to radiation than is the Wilms' tumor and radium radiation can be more easily controlled than X-radiation, it is suggested that scoliosis of genetic or other etiology might be successfully treated by radium or possibly other gamma rays. The choice of the rays and the dosage must be left to the experts.

Animals

Acute necrotizing ulcerative gingivitis. A review of diagnosis, etiology and treatment.

Vincent's original description of the fusiform-spirochete nature of acute necrotizing ulcerative gingivitis (ANUG) still remains true today, although much additional insight has been gained regarding the etiology, pathogenesis and treatment of the disease. In addition to the historic association of fusiform and spirochete microbes with ANUG, recent findings have also implicated Bacteroides and Selenomonas species. Possible abnormalities in immunological function, such as altered PMN and lymphocyte responsiveness, may be present. Stress, which has long been known to be associated with the disease, appears to play a role through induction of increased cortisol and catecholamine levels. These chemical mediators respectively may compromise the host immune responses and the gingival microcirculation. Cortisol may also serve as a nutrient source for Bacteroides bacteria. Other predisposing factors to ANUG may include smoking and poor oral hygiene. Treatment modalities involve eliminating or reducing the levels of bacterial pathogens by mechanical and antibiotic means, along with attempts at controlling significant psychological and physical precipitating factors.

Acquired Immunodeficiency Syndrome

T-cell differentiation antigens and antigenic lymphocyte reactivity in pleural effusions.

Blood and pleural effusion mononuclear cells from thirteen patients were examined for the expression of T lymphocyte differentiation antigens as well as in vitro thymidine incorporation. The ratio of T4 to T8 cells was significantly greater among pleural effusion lymphocytes than among blood lymphocytes. Effusion lymphocyte responses to phytohaemagglutinin were less than those of blood lymphocytes. Unstimulated thymidine incorporation was greater in pleural effusion lymphocytes. Antigen-stimulated lymphocyte reactivity was not consistently greater in either blood or effusion lymphocytes. Lymphocytes from tuberculous effusions all reacted to tuberculin. Pleural effusion lymphocytes, regardless of the etiology of the effusion, possessed the same range of antigenic specificities as did blood lymphocytes. Therefore, effusion lymphocyte responsiveness to tuberculin does not prove the presence of tuberculous pleurisy but does indicate sensitisation to tuberculin.

Adult