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1.
J Bone Joint Surg Am ; 102(Suppl 2): 22-26, 2020 Nov 04.
Article in English | MEDLINE | ID: mdl-32453117

ABSTRACT

BACKGROUND: Ultrasound-assisted measurement of hip flexion has demonstrated that hip flexion has been historically overestimated in men. To our knowledge, assessment of hip flexion in women using similar methods has not been reported. Establishing normative values for hip flexion is vital to aid diagnosis, management, and future research. Therefore, we asked 2 questions: (1) At what range of midsagittal hip flexion do soft-tissue impingement and femoroacetabular abutment occur in asymptomatic young adult women? (2) Do radiographic findings on a supine anteroposterior pelvic radiograph correlate with ultrasound-assisted measurements of hip flexion? METHODS: Fifty-five asymptomatic adult women volunteers (107 hips) underwent ultrasound-assisted assessment of hip flexion. Hip flexion was recorded at the initiation of labral contact and at bone-on-bone contact. Recorded motion was correlated with common radiographic measurements of hip morphology as observed on a supine anteroposterior pelvic radiograph. RESULTS: The mean age of the subjects was 26 ± 3 years (range, 21 to 35 years), and the mean body mass index was 23 ± 3 kg/m (range, 17 to 31.6 kg/m). Mean impingement-free and maximum midsagittal passive flexion were 72° ± 8° (95% confidence interval [CI], 70° to 74°) and 101° ± 11° (95% CI, 99° to 103°), respectively. There were no significant correlations between radiographic measurements of hip morphology and ultrasound-measured hip range of motion. CONCLUSIONS: Observed hip flexion in the asymptomatic hips of young women is substantially less than has been historically reported. Morphologic features that are measurable on anteroposterior pelvic radiographs do not correlate with ultrasound-measured hip flexion. Diagnosis of hip disorders and treatments that are designed to alter hip range of motion should be based on normative data. Future studies regarding surgical restoration and/or preservation of hip flexion should be based on an understanding of normal hip range of motion. CLINICAL RELEVANCE: Ultrasound-assisted hip flexion measurement established normative values to guide surgical restoration and/or preservation of hip flexion.


Subject(s)
Femoracetabular Impingement/physiopathology , Hip Joint/physiopathology , Range of Motion, Articular , Adult , Arthrography , Asymptomatic Diseases , Female , Femoracetabular Impingement/diagnosis , Femoracetabular Impingement/diagnostic imaging , Hip Joint/diagnostic imaging , Humans , Prospective Studies , Range of Motion, Articular/physiology , Ultrasonography , Young Adult
2.
Hernia ; 24(3): 469-479, 2020 06.
Article in English | MEDLINE | ID: mdl-31981010

ABSTRACT

PURPOSE: The aim of this study is to critically examine the multidisciplinary approach to abdominal wall reconstruction (AWR) in the solid organ transplant (SOT) population at our institution, MedStar Georgetown University Hospital, using a modified component separation technique (CST). METHODS: A retrospective review of AWR utilizing modified open CST with biologic mesh in SOT patients was performed from January 2010 to June 2018. Patient demographics, comorbidities, operative details, complications, and outcomes were recorded. Descriptive statistics, logistic and linear regression analyses were performed to appraise outcomes. RESULTS: Thirty-five patients were included; mean age was 53 years. Patient demographics and comorbidities were: 82.9% male, 45.7% history of tobacco use, and 28.6% diabetes. Fifty-one percent had undergone prior hernia repair. Transplant types were: kidney (9), liver (16), liver/kidney (1), small bowel (7), multivisceral (2). All were on an immunosuppressive regimen at time of surgery; 22.9% included steroids. Average defect size was 361 cm2. Additional soft tissue procedures were performed in 65.7% (n = 23) of patients. Median time to healing was 29.0 days. Complication rate was 31.4% (n = 11); six patients required reoperation within 90 days. Recurrence rate was 5.7% (n = 2) at mean of follow up of 3.0 years. Additional soft tissue procedures were statistically significant for healing time (p = 0.037). Steroid use was statistically significant for reoperation within 90 days (OR = 12.500; 95% CI 1.694-92.250); however, steroid use was not significant after correction for confounders. CONCLUSION: Modified open CST with biologic mesh is a safe, efficacious approach to complex AWR in the SOT population with recurrence rates comparable to the general population.


Subject(s)
Abdominal Muscles/surgery , Hernia, Ventral/surgery , Herniorrhaphy , Organ Transplantation , Plastic Surgery Procedures , Surgical Mesh , Abdominal Wall/surgery , Adult , Aged , Bioprosthesis/adverse effects , Female , Hernia, Ventral/etiology , Herniorrhaphy/adverse effects , Herniorrhaphy/methods , Humans , Intestine, Small/transplantation , Kidney Transplantation/adverse effects , Liver Transplantation/adverse effects , Male , Middle Aged , Organ Transplantation/adverse effects , Plastic Surgery Procedures/adverse effects , Plastic Surgery Procedures/methods , Recurrence , Reoperation/adverse effects , Retrospective Studies , Surgical Mesh/adverse effects , Time Factors , Treatment Outcome
3.
Arthroplast Today ; 5(2): 226-233, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31286049

ABSTRACT

BACKGROUND: Mepivacaine as an intermediate-length spinal anesthetic for rapid recovery in total knee arthroplasty (TKA) has not been fully described. We compared spinal mepivacaine vs bupivacaine for postoperative neurologic function in patients undergoing primary TKA. METHODS: Thirty-two patients undergoing primary TKA were enrolled. Primary outcome measure was return of motor and sensory function. Secondary outcome measures included assessment of urinary function, pain via visual analog scale (VAS) scores, opioid usage, distance walked and pain with physical therapy, time to discharge readiness, and complications. RESULTS: Patients with mepivacaine spinal anesthetic had faster return of sensory function (164 ± 38.6 vs 212 ± 54.2 minutes, P = .015), return of motor function (153 ± 47.4 vs 200 ± 45.2 minutes, P = .025), and time to straight leg raise (148 ± 43.5 vs 194 ± 50.8 minutes, P = .023). The mepivacaine group experienced significantly fewer episodes of urinary retention and shorter time to urination (344 ± 154.4 vs 416 ± 96.3 minutes, P = .039). Patients exhibited slightly higher VAS pain scores in the postanesthesia care unit (1.0 ± 1.7 vs 2.7 ± 2.3, P = .046) with no difference in opioid consumption. There were no differences in VAS scores or opioid use on the inpatient ward. Patients achieved discharge readiness 71 minutes faster in the mepivacaine group. There was no need to convert to general anesthesia or transient nerve symptoms in either group. CONCLUSIONS: Patients undergoing TKA with mepivacaine spinal anesthetic had a reliably more rapid neurologic recovery after TKA compared to bupivacaine.

4.
J Arthroplasty ; 33(6): 1699-1704, 2018 06.
Article in English | MEDLINE | ID: mdl-29429882

ABSTRACT

BACKGROUND: Mepivacaine as a spinal anesthetic for rapid recovery in total knee arthroplasty (TKA) has not been assessed. The purpose of this study is to compare spinal mepivacaine vs bupivacaine for postoperative measures in patients undergoing primary TKA. METHODS: Retrospective review of a prospectively collected single-institution database was performed on 156 consecutive patients who underwent primary TKA. Fifty-three patients were administered mepivacaine and 103 patients were administered bupivacaine. Primary outcomes were urinary retention, length of stay, pain control, opioid consumption, and distance associated with physical therapy. Statistical analysis with univariate logistic regression was performed to evaluate the effect of anesthetic with primary outcomes. RESULTS: Patients undergoing TKA with mepivacaine had a shorter length of stay (28.1 ± 11.2 vs 33.6 ± 14.4 hours, P = .002) and fewer episodes of straight catheterization (3.8% vs 16.5%, P = .021) compared to bupivacaine. Patients administered mepivacaine exhibited slightly higher VAS pain scores and morphine consumption in the postanesthesia care unit (1.3 ± 1.9 vs 0.5 ± 1.3, P = .002; 2.2 ± 3.3 vs 0.8 ± 2.1 equivalents/h, P = .002), but otherwise exhibited no difference in VAS scores or morphine consumption afterwards. There was no need to convert to general anesthesia or transient neurologic symptom complication in either group. CONCLUSION: Mepivacaine for spinal anesthesia with TKA had adequate duration to complete the surgery and facilitated a more rapid recovery with less urinary complications and a shorter length of stay. Patients administered mepivacaine did not display worse pain control or transient neurologic symptoms afterwards.


Subject(s)
Anesthesia, Spinal , Anesthetics, Local/administration & dosage , Arthroplasty, Replacement, Knee , Mepivacaine/administration & dosage , Recovery of Function/drug effects , Aged , Analgesics, Opioid/administration & dosage , Anesthesia, General , Bupivacaine/administration & dosage , Bupivacaine/adverse effects , Female , Humans , Male , Mepivacaine/adverse effects , Middle Aged , Morphine/administration & dosage , Pain Management , Pain Measurement , Retrospective Studies , Urinary Retention/chemically induced
5.
JBJS Case Connect ; 6(4): e95, 2016.
Article in English | MEDLINE | ID: mdl-29252749

ABSTRACT

CASE: Atypical presentations of Ewing sarcoma (ES) can lead to misdiagnosis and delays in treatment. We present a rare case of ES in the hand of an adult woman who underwent multiple interventions prior to referral to our institution. At 22 months after definitive treatment, the patient remained pleased with the result and had no evidence of recurrence. CONCLUSION: To our knowledge, ES of the hand in an adult woman has not yet been reported in the literature, and a lack of recognition of this condition might be secondary to the absence of features traditionally associated with malignant bone neoplasms. A broader differential diagnosis after intervention failures offers the opportunity for diagnosis and appropriate treatment.


Subject(s)
Bone Neoplasms/therapy , Metacarpal Bones/surgery , Sarcoma, Ewing/therapy , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/pathology , Female , Humans , Metacarpal Bones/diagnostic imaging , Metacarpal Bones/pathology , Middle Aged , Sarcoma, Ewing/diagnostic imaging , Sarcoma, Ewing/pathology
6.
Br J Dermatol ; 174(4): 862-8, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26663029

ABSTRACT

BACKGROUND: Acne vulgaris is a common condition that occurs in all skin types. Postinflammatory hyperpigmentation (PIH) is often associated with acne in patients of darker skin types, making it a common complaint in dermatology offices. Despite this, there is limited understanding of and effective treatment options for PIH. OBJECTIVES: The study objective was to validate an in vivo model for PIH and to compare the clinical, histological and spectroscopic characteristics of artificially induced PIH and acne-induced PIH. METHODS: A nonblinded, nonrandomized pilot study was performed. Thirty subjects served as their own control in which four sites treated with 35% trichloroacetic acid (TCA) solution and four truncal acne pustules were followed for 8 weeks and were evaluated clinically and histologically, and by colorimetry and spectroscopy. RESULTS: The initial phases of inflammation between TCA- and acne-induced PIH differ. However, clinical evaluations were similar on and after day 14. Acne- and TCA-induced lesions were clinically, histologically and spectroscopically indistinguishable at day 28. CONCLUSIONS: Clinical, spectroscopic and histological similarities of acne-induced and TCA-induced PIH at day 28 suggest that TCA-induced PIH can be a reproducible model for the study of acne-induced PIH.


Subject(s)
Acne Vulgaris/pathology , Hyperpigmentation/pathology , Models, Biological , Adolescent , Adult , Case-Control Studies , Caustics/toxicity , Colorimetry , Erythema/chemically induced , Erythema/pathology , Humans , Hyperpigmentation/chemically induced , Middle Aged , Pilot Projects , Spectrum Analysis , Trichloroacetic Acid/toxicity , Young Adult
7.
Vaccine ; 30(8): 1481-91, 2012 Feb 14.
Article in English | MEDLINE | ID: mdl-22214887

ABSTRACT

Intensive livestock production is associated with an increased incidence of salmonellosis. The risk of infection and the subsequent public health concern is attributed to increased pathogen exposure and disease susceptibility due to multiple stressors experienced by livestock from farm to feedlot. Traditional parenteral vaccine methods can further stress susceptible populations and cause carcass damage, adverse reactions, and resultant increased production costs. As a potential means to address these issues, in-water delivery of live attenuated vaccines affords a low cost, low-stress method for immunization of livestock populations that is not associated with the adverse handling stressors and injection reactions associated with parenteral administration. We have previously established that in-water administration of a Salmonella enterica serovar Typhimurium dam vaccine conferred significant protection in livestock. While these experimental trials hold significant promise, the ultimate measure of the vaccine will not be established until it has undergone clinical testing in the field wherein environmental and sanitary conditions are variable. Here we show that in-water administration of a S. Typhimurium dam attenuated vaccine was safe, stable, and well-tolerated in adult sheep. The dam vaccine did not alter water consumption or vaccine dosing; remained viable under a wide range of temperatures (21-37°C); did not proliferate within fecal-contaminated trough water; and was associated with minimal fecal shedding and clinical disease as a consequence of vaccination. The capacity of Salmonella dam attenuated vaccines to be delivered in drinking water to protect livestock from virulent Salmonella challenge offers an effective, economical, stressor-free Salmonella prophylaxis for intensive livestock production systems.


Subject(s)
Salmonella Infections, Animal/prevention & control , Salmonella Vaccines/administration & dosage , Salmonella Vaccines/immunology , Salmonella typhimurium/genetics , Salmonella typhimurium/immunology , Sheep Diseases/prevention & control , Site-Specific DNA-Methyltransferase (Adenine-Specific)/deficiency , Administration, Oral , Animals , Bacterial Shedding , Drinking Water/microbiology , Microbial Viability , Salmonella Vaccines/adverse effects , Salmonella typhimurium/enzymology , Sheep , Temperature , Vaccination/methods , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/adverse effects , Vaccines, Attenuated/immunology
8.
Vaccine ; 29(19): 3571-82, 2011 Apr 27.
Article in English | MEDLINE | ID: mdl-21473951

ABSTRACT

Stimulation of acquired immunity to Salmonella in livestock is not feasible in neonates (which can be infected within 24h of birth) and is challenging in feedlots, which typically source animals from diverse locations and vendors. Induction of innate immune mechanisms through mass vaccination of animals upon arrival to feedlots is an alternative approach. Transport, environmental conditions, changes in social grouping, and further handling during feedlot assembly are significant stressors. These factors, as well as concurrent exposure to a diversity of pathogens, contribute to the risk of disease. We have shown that oral immunization of calves with a modified live Salmonella enterica serovar Typhimurium vaccine strain, which lacks the DNA adenine methylase gene (S. Typhimurium dam), attenuates the severity of clinical disease, reduces fecal shedding, and promotes clearance of salmonellae following virulent homologous and heterologous challenge. This study examines the safety and efficacy of a S. Typhimurium dam vaccine in sheep via oral delivery in drinking water (ad libitum), as a means to effectively vaccinate large groups of animals. Adult merino sheep were vaccinated in drinking water -28 days, -7 days and 24h pre and 24h post-virulent Salmonella Typhimurium challenge which was administered via the oral route. Significant attenuation of clinical disease (temperature, appetite, and attitude) and reduction in mortality and virulent Salmonella Typhimurium fecal shedding and tissue colonization was observed in animals that received the vaccine 28 and 7 days pre-challenge. Further, vaccination did not pose a risk to stock previously infected with virulent salmonellae as mortalities and clinical disease in sheep vaccinated prior to or following virulent challenge did not differ significantly from the non-vaccinated controls. The capacity of S. Typhimurium dam vaccines delivered in drinking water to protect livestock from virulent Salmonella challenge offers an effective, economical, stressor free Salmonella prophylaxis for intensive livestock production systems.


Subject(s)
Salmonella Infections, Animal/immunology , Salmonella Infections, Animal/prevention & control , Salmonella Vaccines/immunology , Sheep/immunology , Vaccines, DNA/immunology , Animals , Feces/microbiology , Lung/immunology , Lymph Nodes/immunology , Male , Salmonella typhimurium/genetics , Salmonella typhimurium/immunology , Sheep/microbiology , Site-Specific DNA-Methyltransferase (Adenine-Specific)/genetics
9.
Bol. Hosp. Viña del Mar ; 65(1/2): 62-66, ene. 2009. tab
Article in Spanish | LILACS | ID: lil-545874

ABSTRACT

Un acceso fácil y sin costo a revistas médicas en INTERNET a través de la Fundación Ginebra de Educación Médica e Investigación, la que facilita a médicos y otros profesionales de la Salud acceso a una biblioteca completa para investigar y revisar artículos, permitiéndoles crear sus propios programas de Educación Médica Contínua


An easy approach to free medical journals in INTERNET through the non profit contribution of the Geneva Foundation for Medical Education and Research, which facilitates doctors and other health related professionals access to a complete library of research and review articles, allowing them to create a self oriented program of Continued Medical Education.


Subject(s)
Education, Medical, Continuing , Internet , Periodicals as Topic , Portals for Scientific Journals
10.
Vaccine ; 26(14): 1751-8, 2008 Mar 25.
Article in English | MEDLINE | ID: mdl-18329764

ABSTRACT

Intensive livestock production and management systems are associated with increased fecal-oral pathogen transmission and a resultant high prevalence of multiple Salmonella serovars in many large dairy farms and feedlots. Thus, it is imperative to develop livestock vaccines that are capable of eliciting potent states of cross-protective immunity against a diversity of serovars of a given species. Immunization with modified live Salmonella enterica serovar Typhimurium vaccine strains, that lack the DNA adenine methylase (Dam), confers cross-protective immunity in murine and avian models of typhoid fever as well as in a bovine model of salmonellosis. Here we examined whether a dam mutant Typhimurium vaccine (serogroup B) has the capacity to elicit cross-protection against a virulent challenge with an emerging, clinically relevant, and multi-drug resistant strain of serovar Newport (serogroup C2-C3) that has been associated with clinical disease in recent salmonellosis outbreaks in calves. Vaccinated animals challenged with Newport exhibited a significant attenuation of clinical disease (improved attitude scores, increased daily weight gains and reduced fever and diarrhea) and a concomitant reduction in Newport fecal shedding and colonization of mesenteric lymph nodes and lungs compared to non-vaccinated control animals. The capacity to elicit cross-protective immunity in calves suggests that dam mutant vaccines have potential application toward the prevention and control of Salmonella infection in commercial livestock production systems wherein livestock are exposed to a diversity of Salmonella serovars.


Subject(s)
Cattle Diseases/immunology , Salmonella Infections, Animal/immunology , Salmonella Vaccines/genetics , Salmonella Vaccines/immunology , Salmonella typhimurium/genetics , Salmonella typhimurium/immunology , Site-Specific DNA-Methyltransferase (Adenine-Specific)/genetics , Animals , Cattle , Cattle Diseases/prevention & control , Cross Reactions , Feces/microbiology , Immunity/immunology , Lung/microbiology , Lymph Nodes/microbiology , Mesentery/microbiology , Salmonella Infections, Animal/prevention & control
12.
Fitoterapia ; 75(1): 68-73, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14693223

ABSTRACT

Seventy-two extracts (methanol) obtained from the leaves, barks, and roots of 50 plant species used in the traditional medicine of Perak, Peninsular Malaysia, have been screened for antibacterial and antifungal activities. Peristrophe tinctoria, Polyalthia lateriflora, Knema malayana, Solanum torvum, Celosia argentea, Eclipta prostrata, Ancistrocladus tectorius, Dillenia suffruticosa, Piper stylosum and Rafflesia hasseltii displayed the broadest spectrum of activity.


Subject(s)
Anti-Infective Agents/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Phytotherapy , Plant Extracts/pharmacology , Plants, Medicinal , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/therapeutic use , Humans , Malaysia , Medicine, Traditional , Microbial Sensitivity Tests , Mitosporic Fungi/drug effects , Plant Bark , Plant Extracts/administration & dosage , Plant Extracts/therapeutic use , Plant Leaves , Plant Roots
13.
Vaccine ; 21(23): 3249-58, 2003 Jul 04.
Article in English | MEDLINE | ID: mdl-12804855

ABSTRACT

Salmonellosis is an important disease of livestock and Salmonella contamination of livestock-derived food products and effluents pose a significant risk to human health. Salmonella vaccines currently available to prevent salmonellosis in cattle have limited efficacy. Here we evaluated a Salmonella enterica serovar Typhimurium vaccine strain lacking the DNA adenine methylase (Dam) for safety and efficacy in calves. Vaccination was safe in calves, and following challenge with virulent Typhimurium 4 weeks post-immunization, vaccinated animals exhibited significantly lower mortality, diarrhea, and rectal temperatures, as well as reduced colonization of gastrointestinal tract and visceral organs compared to non-vaccinated control animals. Additionally, early onset protection (competitive exclusion) in vaccinated neonatal calves was demonstrated by attenuated clinical disease (as measured by rectal temperatures and attitude scores) and reduced mortality when challenged with virulent Typhimurium 24h after immunization. Taken together, these data suggest that vaccination with Salmonella Dam mutant strains confer significant protection against Salmonella infections in cattle via both adaptive immunity and competitive exclusion mechanisms.


Subject(s)
Bacterial Vaccines/immunology , Cattle Diseases/prevention & control , Salmonella Infections/prevention & control , Salmonella enterica/enzymology , Salmonella enterica/genetics , Site-Specific DNA-Methyltransferase (Adenine-Specific)/genetics , Animals , Cattle , Cattle Diseases/immunology , Feces/microbiology , Intestines/microbiology , Mutation/genetics , Mutation/immunology , Salmonella Infections/immunology , Salmonella enterica/growth & development , Vaccination
14.
Int J Food Microbiol ; 80(2): 153-9, 2003 Jan 25.
Article in English | MEDLINE | ID: mdl-12381401

ABSTRACT

Salmonella mutants lacking DNA adenine methylase (Dam) are highly attenuated for virulence and confer protection against oral challenge with homologous and heterologous Salmonella serovars in mice and chicken broilers. To determine whether vaccines based on Dam are efficacious in preventing early colonization of newly hatched chickens, a Salmonella typhimurium Dam(-) vaccine was evaluated for the protection of chicks against oral challenge with homologous and heterologous Salmonella serovars. Vaccination of chicks elicited protection 2 and 6 days post-challenge as evidenced by a significant reduction in colonization of the gastrointestinal tract (ileum, cecum and feces) and visceral organs (spleen and bursa) when challenged with homologous S. typhimurium. Moderate protection was observed following challenge with heterologous S. enteritidis and Salmonella O6, 14, 24:e, h-monophasic) serovars. These data suggest that Salmonella Dam mutant strains conferred cross-protection, presumably via competitive exclusion mechanisms that prevent superinfection of chicks by other Salmonella strains. Such protection may reduce pre-harvest Salmonella contamination in poultry, decreasing the potential for food-borne transmission of this pathogen to humans.


Subject(s)
Chickens , Poultry Diseases/prevention & control , Salmonella Infections, Animal/prevention & control , Salmonella/immunology , Site-Specific DNA-Methyltransferase (Adenine-Specific)/genetics , Animals , Mutation , Random Allocation , Salmonella/genetics , Salmonella Vaccines/immunology , Serotyping , Vaccination/veterinary , Vaccines, Attenuated
16.
Infect Immun ; 69(12): 7610-5, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11705940

ABSTRACT

Salmonella strains that lack or overproduce DNA adenine methylase (Dam) elicit a protective immune response to different Salmonella species. To generate vaccines against other bacterial pathogens, the dam genes of Yersinia pseudotuberculosis and Vibrio cholerae were disrupted but found to be essential for viability. Overproduction of Dam significantly attenuated the virulence of these two pathogens, leading to, in Yersinia, the ectopic secretion of virulence proteins (Yersinia outer proteins) and a fully protective immune response in vaccinated hosts. Dysregulation of Dam activity may provide a means for the development of vaccines against varied bacterial pathogens.


Subject(s)
Bacterial Vaccines/therapeutic use , Site-Specific DNA-Methyltransferase (Adenine-Specific)/genetics , Vibrio cholerae/pathogenicity , Yersinia pseudotuberculosis/pathogenicity , Animals , Bacterial Outer Membrane Proteins/metabolism , Bacterial Vaccines/genetics , Cholera/prevention & control , Cholera Vaccines/genetics , Cholera Vaccines/therapeutic use , Gene Expression Regulation, Bacterial , Mice , Molecular Sequence Data , Recombinant Proteins/biosynthesis , Site-Specific DNA-Methyltransferase (Adenine-Specific)/biosynthesis , Vibrio cholerae/physiology , Yersinia pseudotuberculosis/physiology , Yersinia pseudotuberculosis Infections/prevention & control
17.
Infect Immun ; 69(12): 7950-4, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11705984

ABSTRACT

Salmonella DNA adenine methylase (Dam) mutants that lack or overproduce Dam are highly attenuated for virulence in mice and confer protection against murine typhoid fever. To determine whether vaccines based on Dam are efficacious in poultry, a Salmonella Dam(-) vaccine was evaluated in the protection of chicken broilers against oral challenge with homologous and heterologous Salmonella serovars. A Salmonella enterica serovar Typhimurium Dam(-) vaccine strain was attenuated for virulence in day-of-hatch chicks more than 100,000-fold. Vaccination of chicks elicited cross-protective immune responses, as evidenced by reduced colonization (10- to 10,000-fold) of the gastrointestinal tract (ileum, cecum, and feces) and visceral organs (bursa and spleen) after challenge with homologous (Typhimurium F98) and heterologous (Enteritidis 4973 and S. enterica O6,14,24: e,h-monophasic) Salmonella serovars that are implicated in Salmonella infection of poultry. The protection conferred was observed for the organ or the maximum CFU/tissue/bird as a unit of analysis, suggesting that Dam mutant strains may serve as the basis for the development of efficacious poultry vaccines for the containment of Salmonella.


Subject(s)
Salmonella Infections, Animal/prevention & control , Salmonella Vaccines/therapeutic use , Salmonella typhimurium , Site-Specific DNA-Methyltransferase (Adenine-Specific)/genetics , Vaccination/veterinary , Animals , Chickens , Cross Reactions , Mutation , Salmonella/classification , Salmonella/immunology , Salmonella Infections, Animal/immunology , Salmonella Vaccines/genetics , Salmonella Vaccines/immunology , Serotyping , Vaccines, Attenuated/genetics , Vaccines, Attenuated/immunology , Vaccines, Attenuated/therapeutic use
18.
Infect Immun ; 69(11): 6725-30, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11598044

ABSTRACT

Salmonella isolates that lack or overproduce DNA adenine methylase (Dam) elicited a cross-protective immune response to different Salmonella serovars. The protection afforded by the Salmonella enterica serovar Typhimurium Dam vaccine was greater than that elicited in mice that survived a virulent infection. S. enterica serovar Typhimurium Dam mutant strains exhibited enhanced sensitivity to mediators of innate immunity such as antimicrobial peptides, bile salts, and hydrogen peroxide. Also, S. enterica serovar Typhimurium Dam(-) vaccines were not immunosuppressive; unlike wild-type vaccines, they failed to induce increased nitric oxide levels and permitted a subsequent robust humoral response to diptheria toxoid antigen in infected mice. Dam mutant strains exhibited a low-grade persistence which, coupled with the nonimmunosuppression and the ectopic protein expression caused by altered levels of Dam, may provide an expanded source of potential antigens in vaccinated hosts.


Subject(s)
Salmonella Infections, Animal/prevention & control , Salmonella/enzymology , Site-Specific DNA-Methyltransferase (Adenine-Specific)/immunology , Animals , Bacterial Proteins/biosynthesis , Cross Reactions , Immune Tolerance/immunology , Mice , Mice, Inbred BALB C , Mucous Membrane/immunology , Mucous Membrane/microbiology , Mutagenesis , Salmonella/immunology , Salmonella/pathogenicity , Salmonella Vaccines/immunology , Salmonella typhimurium/immunology , Salmonella typhimurium/pathogenicity , Serotyping , Site-Specific DNA-Methyltransferase (Adenine-Specific)/genetics , Virulence
19.
Annu Rev Genet ; 34: 139-164, 2000.
Article in English | MEDLINE | ID: mdl-11092824

ABSTRACT

A number of techniques have been developed to assess the expression of microbial virulence genes within the host (in vivo). These studies have shown that bacteria employ a wide variety of mechanisms to coordinately regulate the expression of these genes during infection. Two tenets have emerged from these studies: bacterial adaptation responses are critical to growth within the host, and interactions between microorganisms and the microenvironments of their hosts cannot be revealed from in vitro studies alone. Results that support these tenets include (i) the prevalent class of in vivo expressed genes are involved in adaptation to environmental stresses, (ii) pathogens recovered from host tissues (versus laboratory growth) are often more resistant to host killing mechanisms, and (iii) virulence gene expression can differ in the animal compared to laboratory media. Thus, pathogenicity comprises the unique ability to adapt to the varied host milieus encountered as the infection proceeds.


Subject(s)
Bacteria/genetics , Gene Expression , Bacteria/pathogenicity , Bacterial Infections/genetics , Genes, Bacterial , Virulence/genetics
20.
Science ; 288(5471): 1635-40, 2000 Jun 02.
Article in English | MEDLINE | ID: mdl-10834841

ABSTRACT

Blood cell production originates from a rare population of multipotent, self-renewing stem cells. A genome-wide gene expression analysis was performed in order to define regulatory pathways in stem cells as well as their global genetic program. Subtracted complementary DNA libraries from highly purified murine fetal liver stem cells were analyzed with bioinformatic and array hybridization strategies. A large percentage of the several thousand gene products that have been characterized correspond to previously undescribed molecules with properties suggestive of regulatory functions. The complete data, available in a biological process-oriented database, represent the molecular phenotype of the hematopoietic stem cell.


Subject(s)
Gene Expression Profiling , Genes , Hematopoietic Stem Cells/physiology , Proteins/genetics , Proteins/physiology , Amino Acid Sequence , Animals , Computational Biology , Databases, Factual , Expressed Sequence Tags , Gene Library , Hematopoietic Stem Cells/chemistry , Hematopoietic Stem Cells/cytology , Liver/cytology , Liver/embryology , Membrane Proteins/chemistry , Membrane Proteins/genetics , Membrane Proteins/physiology , Mice , Molecular Sequence Data , Polymerase Chain Reaction , Proteins/chemistry , Signal Transduction , Transcription Factors/chemistry , Transcription Factors/genetics , Transcription Factors/physiology
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