Implementing a new predoctoral curriculum with a PBL component at Indiana University School of Dentistry.
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Curriculum↗
Biomedical subjects
M S Lantz
Publications and source records attributed to M S Lantz.
The Wellness Group: a novel intervention for coping with disruptive behavior among [corrected] elderly nursing home residents.
Elderly nursing home residents face the challenge of coping with the loss of independence, reduced physical abilities, feelings of isolation, anxiety, depression, and helplessness. Maintaining one's integrity within the nursing home is a challenge easily lost. Issues of coping with disability, change in body image, the promotion of self-empowerment, and autonomy are critical to preserving the personhood of a nursing home resident. Current emphasis on the management of behavior has focused entirely on the control of disruption rather than the promotion of resident strengths and abilities. We developed a group therapy program designed to enhance self-awareness, self-esteem, and body awareness among the demented elderly. Techniques of meditation, relaxation, sensory awareness and guided imagery were introduced and reinforced. This group is easily reproducible and offers benefits to both residents and interdisciplinary staff.
Aged↗
Are bacterial proteases important virulence factors?
The contribution of bacterial proteases to virulence has been relatively understudied. It is a simple matter to argue that bacterial proteases have the potential to destroy the structural and functional proteins that constitute host tissues as well as to destroy proteins important in host defense. Systematically demonstrating that such interactions occur during disease pathogenesis is more difficult, although a few studies have suggested that the ability of a pathogen to use proteases to cross proteinaceous barriers within the host contributes to bacterial virulence. This manuscript reviews concepts of bacterial virulence. Next, it describes how the host regulates the activities of its own proteases to maintain a state of health, and examines evidence suggesting that dysregulation of host proteases results in disease. Finally, evidence supporting a role for endogenous microbial proteases or acquisition of host proteases by microbes as virulence determinants is discussed as are suggestions for future directions for research in this area.
Animals↗
What should biomedical sciences education in dental schools achieve?
Education for the first professional degree in dentistry is intended to produce graduates capable of offering a wide range of high quality dental services to the general public. More than that, it is expected that graduates will be firmly grounded in the scientific basis for their professional practices and be equipped to evaluate critically and integrate selectively new scientific findings that emerge during their professional lifetimes. In addition, they are expected to be able to work effectively with diverse patient populations and to conduct their practices with a high level of sensitivity to the ethical and psychosocial dimensions of patient care. Indiana University School of Dentistry has undergone a process of curriculum reform that has yielded a new first professional degree program. Its hallmarks are large, multidisciplinary courses (seven courses in the first two years) that are taught using a variety of strategies including problem-based learning in small groups as well as lectures. The biomedical sciences curriculum is concept-based. Students will demonstrate their understanding of science concepts and methods by applying them to the solution of research and health care problems. Biomedical sciences will be taught at a level that will provide a comprehensive understanding of the functioning of the human body in health and disease, allow students to assimilate the coming revolution in molecular medicine, and selectively use new diagnostics, preventives, and therapeutics that evolve as molecular biological technologies yield solutions to current medical and dental problems. Using the biomedical sciences curriculum as a vehicle, we will also achieve the goal of training dentists as critical thinkers, problem solvers, lifelong learners, and ethical practitioners, skillful in peer and self-evaluation, and cognizant of the psychosocial as well as biomedical perspective of health and disease.
Biological Science Disciplines↗
Efficacy and tolerability of tacrine in nursing home residents with Alzheimer's dementia.
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Aged↗
Analysis of the prtP gene encoding porphypain, a cysteine proteinase of Porphyromonas gingivalis.
The cloning and sequencing of the gene encoding porphypain, a cysteine proteinase previously isolated from detergent extracts of the Porphyromonas gingivalis W12 cell surface, are described. The prtP gene encoded a unique protein of 1,732 amino acids, including a putative signal sequence for protein secretion. The predicted molecular mass for the mature protein was 186 kDa, which was close to the observed molecular mass of 180 kDa. There was one copy of prtP in the genomes of seven P. gingivalis strains examined. The gene was located 5' to a region with a high degree of homology to the insertion element IS1126 in P. gingivalis W12. The PrtP protein had regions of high homology to HagA, a hemagglutinin of P. gingivalis, and to several purported proteinases of P. gingivalis that have Arg-X specificity. A detailed comparison of genes encoding the latter and cpgR suggested that rgp-1, prpR1, prtR, agp, cpgR, and possibly prtH were derived from identical genetic loci. Although an rgp-1-like locus was detected in seven P. gingivalis strains by Southern blot analyses, agp and cpgR were not detected, not even in the strains from which they were originally isolated. In addition, at least 20 copies of a repeat region common to PrtP, the Rgp-1-like proteins, and HagA were observed in each of the seven genomes examined. The repeat region hybridization patterns for strains W83 and W50 were very similar, and they were identical for strains 381 and ATCC 33277, providing further evidence that these strains are closely related genetically.
Amino Acid Sequence↗
A ten-year review of the effect of OBRA-87 on psychotropic prescribing practices in an academic nursing home.
OBJECTIVE: The Omnibus Budget Reconciliation Act of 1987 (OBRA-87) included provisions for regulating the use of psychotropic medication, particularly antipsychotics, in long-term-care facilities. The study examined the effect of OBRA-87 on patterns of prescribing of psychotropic medication in a 514-bed nursing home affiliated with a large medical school. METHODS: Computerized pharmacy records for the ten-year period from March 1984 through July 1994 were retrospectively reviewed to identify orders written for psychotropic medications and to determine the percentage of nursing home residents who received prescriptions for those agents and the average daily dose of the most frequently prescribed agents. RESULTS: During the period before implementation of the regulations, the percentages of residents who received antidepressants, anxiolytic and sedative-hypnotic medications, and antipsychotic medications were stable. After implementation, prescription of antidepressants increased significantly, coinciding with a reduction in prescription of anxiolytics and sedative-hypnotics and a substantial decrease in prescription of antipsychotics. The total number of residents who received any type of psychotropic medication decreased, and over time a trend toward prescription of agents recommended for geriatric use, such as short-acting benzodiazepines and tertiary tricyclic antidepressants, emerged. CONCLUSIONS: The changes that resulted from the OBRA-87 regulations reffect both the restrictions placed on classes of medication and the prevalence of psychiatric disorders in the nursing home. In this facility, OBRA-87 appears to have served as an impetus for clinical review and change in practice style.
Aged↗
Pharmacologic treatment of agitation in dementia: a comprehensive review.
Agitated behaviors are a common and nearly universal occurrence among patients suffering from dementing illnesses. The pharmacologic treatments available for this troubling syndrome are varied, but treatment studies are limited. Clinicians are frequently faced with the challenging management of patients with disruptive behavior who fail to respond to trials with multiple agents. This review summarizes available treatment studies of agitation in dementia and offers a guide to therapy and management. Reports of therapies for agitation in dementia are limited by lack of controlled studies, variability of diagnostic criteria and outcome measures, and small sample size. The need for carefully designed, well-controlled studies of outcome in this growing population is formidable. It is imperative to identify effective and well-tolerated treatment strategies to reduce the morbidity of these distressing and burdensome symptoms.
Adrenergic beta-Antagonists↗
New insights into mechanisms of bacterial pathogenesis in periodontitis.
This review focuses on two topics that in the past decade have significantly enhanced our understanding of the mechanisms by which bacteria produce disease in humans: population structures of bacterial pathogens and tactics used by these bacteria to gain entry to mammalian cells. Studies in these areas have identified a number of virulence factors of some medically important pathogens. Very recent applications of this knowledge in efforts to understand mechanisms by which the most extensively studied "putative" periodontal pathogens, Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans, may contribute to the pathogenesis of periodontitis are presented. Knowledge of the population structures of these periodontopathic bacterial species and the mechanisms used by these bacteria to subvert host cell communication systems and functions will shape future approaches to diagnosis, prevention, and treatment of periodontal diseases.
Aggregatibacter actinomycetemcomitans↗
The psychiatrist in the nursing home, Part I: Collaborative roles.
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Aged↗
Alzheimer's disease: how to give and monitor tacrine therapy.
Up to one-third of patients with mild to moderate Alzheimer's disease may show improvement in cognitive function with tacrine, a centrally-acting, noncompetitive inhibitor of acetylcholinesterase. Candidates for tacrine must have a diagnosis of probable Alzheimer's dementia based on NINCDS-ADRDA or DSM-IV criteria and should have no history of liver disease. For patients receiving the drug, do follow-up cognitive testing with a sensitive measure such as the Alzheimer's Disease Assessment Scale. The most common adverse effects associated with tacrine therapy are elevated liver transaminases and gastrointestinal effects. Weekly blood tests are necessary to monitor liver function. A reliable caregiver is essential to ensure compliance with frequent dosing and weekly blood testing.
Activities of Daily Living↗
Zymographic techniques for detection and characterization of microbial proteases.
We have presented a variety of zymographic techniques for identification and characterization of microbial proteases, using SDS-PAGE and PAGE in nondissociating gels. Techniques are described using copolymerized protein substrates, diffusable protein substrates, protein substrates incorporated into indicator gels, as well as synthetic esterase substrates. When a newly discovered protease is being characterized, it is advisable to try a variety of techniques, both to determine optimal conditions for enzyme detection and to characterize the protease. Zymography is a versatile two-stage technique involving protein separation by electrophoresis followed by detection of proteolytic activity. Each particular combination of protease separation and detection techniques had advantages and limitations. Protease separation by SDS-PAGE has as a limitation the fact that some proteases do not renature and hence cannot be detected following treatment with SDS. However, it has an advantage the fact that it allows estimation of the relative molecular weight of proteases. Protein separation using nondissociating PAGE is performed using much gentler protease inactivation conditions than those produced by treatment with SDS. Like SDS-PAGE, nondissociating PAGE permits detection of multiple forms of enzymes; however, a disadvantage is that it cannot be used to obtain molecular weight estimates of proteases. The main variable to control during development of zymograms is the length of time of incubations. Increasing incubation (development) time generally increases the sensitivity of protease detection; however, as the length of time of incubation increases so does the extent of diffusion of proteases and substrates. If incubations are prolonged, protease bands will diffuse, decreasing resolution. Additionally, zones of lysis produced by closely migrating proteolytically active species will merge, eliminating the possibility of detecting all proteolytic species in the sample. Zymographic techniques can be extremely useful in identification and characterization of microbial proteases. If a few properties of a protease are known, such as the pH range over which the enzyme is active, and whether it can renature after exposure to SDS, zymographic techniques can be specifically and readily adapted to optimize conditions for detection and assist in characterization of the enzyme.
Amino Acid Sequence↗
Purification and characterization of two forms of a high-molecular-weight cysteine proteinase (porphypain) from Porphyromonas gingivalis.
Porphyromonas gingivalis, and organism implicated in the etiology and pathogenesis of human periodontal diseases, produces a variety of potent proteolytic enzymes, and it has been suggested that these enzymes play a direct role in the destruction of periodontal tissues. We now report that two cell-associated cysteine proteinases of P. gingivalis W12, with molecular masses of approximately 150 kDa (porphypain-1) and 120 kDa (porphypain-2), as determined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, have been separated and purified to apparent homogeneity. These proteinases appear to be SDS-stable conformational variants of a 180-kDa enzyme, and they are the largest cysteine proteinases yet purified from P. gingivalis. The purified proteinases hydrolyze fibrinogen, tosyl-Gly-L-Pro-L-Arg p-nitroanilide, and tosyl-Gly-L-Pro-L-Lys p-nitroanilide. While hydrolysis of both synthetic substrates by porphypain-1 and -2 requires activation by reducing agents, is inhibited by EDTA, and is stimulated in the presence of derivatives of glycine, the Arg-amidolytic activity is sensitive to leupeptin and H-D-tyrosyl-L-prolyl-L-arginyl chloromethyl ketone, whereas the Lys-amidolytic activity is sensitive to tosyl-L-lysyl chloromethyl ketone and insensitive to leupeptin. These data suggest that porphypains contain two types of active sites. These cell-associated P. gingivalis proteinases may contribute significantly and directly to periodontal tissue destruction.
Amino Acid Sequence↗
Purification and immunolocalization of a cysteine protease from Porphyromonas gingivalis.
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Cysteine Endopeptidases↗
Collagen mediates adhesion of Streptococcus mutans to human dentin.
Some strains of Streptococcus mutans were found to recognize and bind collagen type I. Binding of 125I-labeled collagen type I was specific in that collagen types I and II, but not unrelated proteins, were able to inhibit binding of the labeled ligand to bacteria. Collagen binding to S. mutans was partially reversible and involved a limited number of bacterial binding sites per cell. S. mutans UA 140 cells bound collagen type I with high affinity (Kd = 8 x 10(-8) M). The number of binding sites per cell was 4 x 10(4). Collagen-binding strains of S. mutans were found to adhere to collagen-coated surfaces as well as to pulverized root tissue. S. mutans strains that did not bind the soluble ligand were unable to adhere to these substrata. Adherence to collagen-coated surfaces could be inhibited with collagen or clostridial collagenase-derived collagen peptides. Adherence of S. mutans to dentin was enhanced by collagen types I and II but inhibited by collagen peptides. S. mutans UA 140 bound significantly less 125I-collagen type I following treatment with peptidoglycan-degrading enzymes. These enzymes released a collagen-binding protein (collagen receptor) with a relative molecular size of 16 kDa. The results of this study suggest that collagen mediates adhesion of S. mutans to dentin. This interaction may target collagen-binding strains of S. mutans to dentin in the oral cavity and may play a role in the pathogenesis of root surface caries.
Adhesins, Bacterial↗
Porphyromonas gingivalis surface components bind and degrade connective tissue proteins.
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Autoradiography↗
Identification of Porphyromonas gingivalis components that mediate its interactions with fibronectin.
Porphyromonas (Bacteroides) gingivalis W12 binds and degrades human plasma fibronectin. In the presence of the protease inhibitor N-alpha-p-tosyl-L-lysyl chloromethyl ketone, P. gingivalis cells accumulated substantial amounts of 125I-fibronectin as a function of incubation time. Fibronectin binding was specific, reversible, and saturable. The Kd for the reaction was estimated to be on the order of 100 nM, and there was an average of 3.5 x 10(3) fibronectin binding sites per cell. Unlabeled fibronectin inhibited the binding of 125I-fibronectin to bacteria; however, fibrinogen was an even more efficient inhibitor of 125I-fibronectin binding. Unrelated proteins were without effect on fibronectin binding. A fibronectin-binding component (Mr, 150,000) was identified in sodium dodecyl sulfate-solubilized P. gingivalis. Fibronectin was degraded into discrete peptides by P. gingivalis W12. The degradation of fibronectin was inhibited by N-alpha-p-tosyl-L-lysyl chloromethyl ketone. Two P. gingivalis components (Mrs, 120,000 and 150,000) degraded fibronectin in substrate-containing gels following sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In a previous study (M. S. Lantz, R. D. Allen, T. A. Vail, L. M. Switalski, and M. Hook, J. Bacteriol. 173:495-504, 1991), we found that the same strain of P. gingivalis bound and subsequently degraded human fibrinogen via apparently distinct cell surface components of molecular sizes similar to those of components now implicated in the binding and degradation of fibronectin. These results raise the possibility that the two ligands are recognized and modified by the same components on P. gingivalis W12. In support of this hypothesis, unlabeled fibrinogen effectively inhibited the binding of 125I-fibronectin to bacteria and blocked 125I-fibronectin binding to a P. gingivalis ligand-binding component (Mr, 150,000 immobilized on a nitrocellulose membrane.
Bacteroides↗
Specific cell components of Bacteroides gingivalis mediate binding and degradation of human fibrinogen.
Bacteroides (Porphyromonas) gingivalis, which has been implicated as an etiologic agent in human periodontal diseases, has been shown to bind and degrade human fibrinogen. B. gingivalis strains bind fibrinogen reversibly and with high affinity and bind to a specific region of the fibrinogen molecule that appears to be located between the D and E domains (M. S. Lantz, R. D. Allen, P. Bounelis, L. M. Switalski, and M. Hook, J. Bacteriol. 172:716-726, 1990). We now report that human fibrinogen is bound and then degraded by specific B. gingivalis components that appear to be localized at the cell surface. Fibrinogen binding to bacterial cells occurred at 4, 22, and 37 degrees C. A functional fibrinogen-binding component (Mr, 150,000) was identified when sodium dodecyl sulfate-solubilized bacteria were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose membranes, and probed with 125I-fibrinogen. Fibrinogen degradation did not occur at 4 degrees C but did occur at 22 and 37 degrees C. When bacteria and iodinated fibrinogen were incubated at 37 degrees C, two major fibrinogen fragments (Mr, 97,000 and 50,000) accumulated in incubation mixture supernatant fractions. Two major fibrinogen-degrading components (Mr, 120,000 and 150,000) have been identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in substrate-containing gels. Fibrinogen degradation by the Mr-120,000 and -150,000 proteases was enhanced by reducing agents, completely inhibited by N-alpha-p-tosyl-L-lysyl chloromethyl ketone, and partially inhibited by n-ethyl maleimide, suggesting that these enzymes are thiol-dependent proteases with trypsinlike substrate specificity. The fibrinogen-binding component could be separated from the fibrinogen-degrading components by selective solubilization of bacteria in sodium deoxycholate.
Bacterial Proteins↗