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1.
Vet Ophthalmol ; 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38468143

ABSTRACT

OBJECTIVE: To describe ophthalmic findings in hospitalized canine and feline patients with tick paralysis (TP) and investigate possible predisposing factors. ANIMALS STUDIED: Forty-seven dogs and 28 cats hospitalized with TP assessed with an ophthalmic examination performed by an ABVO resident. METHODS: Dogs and cats were hospitalized with TP from October 2021 to January 2022 and had an ophthalmic examination performed by an ABVO resident. Patient signalment data, information regarding tick number and location, hospitalization duration, medications used, and patient paralysis grades were recorded. Statistical analysis was performed to correlate findings. RESULTS: Corneal ulcers developed in up to 34.8% of dogs and up to 42.9% of cats hospitalized with TP. An absent palpebral reflex ipsilaterally increased the odds of a concurrent corneal ulcer being present by 14.7× in dogs and 20.1× in cats (p < .0001). Palpebral reflexes were absent in 38.3% of dogs and 35.7% of cats hospitalized with TP and were correlated with more severe gait paralysis (p = .01) and respiratory paralysis (p = .005) in dogs, and respiratory paralysis in cats (p = .041). STT-1 findings <10 mm/min were present in 27.7% of dogs and 57.1% of cats examined and were associated with increasing gait paralysis (p = .017) and respiratory paralysis (p = .007) in dogs, and increasing gait paralysis in cats (p = .017). CONCLUSIONS: Simple corneal ulcers, loss of a complete palpebral reflex, and reduced STT-1 scores frequently occurred in dogs and cats hospitalized for TP. The frequency of these findings increased as the degree of patient paralysis increased.

2.
Aust Vet J ; 102(6): 296-305, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38369322

ABSTRACT

OBJECTIVE: To investigate the incidence and predisposing factors leading to the development of corneal ulcers and the loss of a palpebral reflex in hospitalised canine and feline patients with tick paralysis (TP). ANIMALS STUDIED: A total of 102 dogs and 100 cats retrospectively were assessed from previously hospitalised patients. METHODS: A retrospective cohort study was performed on 102 different canine and 100 different feline patients who were hospitalised for TP from October 2020-January 2022. Patient data were collected, and logistic regression was conducted to determine factors affecting the palpebral reflex and the development of corneal ulcers. RESULTS: Corneal ulcers occurred in 23/102 (22.5%) dogs during hospitalisation and were strongly associated with an incomplete palpebral reflex ipsilaterally during hospitalisation (P < 0.001), hospitalisation ≥3 days (P = 0.004), mechanical ventilation ≥3 days (P = 0.015) or a tick location cranial to C1 (P = 0.003). An incomplete palpebral reflex during hospitalisation was observed in 29/102 (28.4%) dogs and was significantly associated with decreasing patient weight (P = 0.018), increasing days hospitalised (P = 0.001), having a tick found cranial to C1 (P = 0.004), highest recorded GP grade (P = 0.01), highest recorded RP grade (P = 0.005), use of amoxycillin-clavulanic acid during hospitalisation (P = 0.002) and use of piperacillin/tazobactam during hospitalisation (P = 0.003). There was a significant association between the loss of a complete palpebral reflex and mortality during hospitalisation in dogs (OR = 4.5, P = 0.029). Corneal ulcers occurred in 10/100 (10.0%) cats during hospitalisation, and was significantly more likely to occur to an eye if an incomplete palpebral reflex was observed ipsilaterally during hospitalisation (OR = 20.1, P < 0.0001) and with increasing patient age (P = 0.019). The absence of a complete palpebral reflex during hospitalisation was observed in 18/10 (18.0%) cats and was significantly associated with increasing days hospitalised (P = 0.034). There was no significant association between the loss of a complete palpebral reflex and mortality during hospitalisation in cats. CONCLUSIONS: The frequency of corneal ulcers and loss of palpebral reflexes were significant in dogs and cats hospitalised by TP, with many factors contributing to the risk of these developing.


Subject(s)
Cat Diseases , Corneal Ulcer , Dog Diseases , Ixodes , Tick Paralysis , Animals , Dogs , Cats , Dog Diseases/drug therapy , Retrospective Studies , Cat Diseases/drug therapy , Tick Paralysis/veterinary , Female , Male , Corneal Ulcer/veterinary , Hospitalization/statistics & numerical data , Cohort Studies , Incidence , Risk Factors
3.
Vet Ophthalmol ; 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38424032

ABSTRACT

OBJECTIVE: To describe the clinical features of cats diagnosed with distichiasis and report on the outcomes following cryoepilation. ANIMALS STUDIED: Fifteen cats (27 eyes). PROCEDURES: Medical records of domestic cats with distichiasis that underwent a double freeze-thaw cycle with a -80°C cryoprobe applied to the palpebral conjunctiva, with hair then epilated were retrospectively studied. The patient signalment, distichiae locations, concurrent ocular diseases, recurrences, complications, and outcomes were recorded. RESULTS: The mean (std dev) age at the time of diagnosis and treatment was 2.2 years (2.8 years). All (15/15) cats were of the domestic shorthair (DSH) breed. Concurrent ocular findings at the initial examination were observed in 17/27 (63%) eyes, with upper lateral eyelid hypoplasia the most prevalent, present in 9/27 (33.3%) eyes. Recurrence of distichiae occurred in 8/27 (29.6%) eyes. The clinical presentation in the instances of recurrence was judged as asymptomatic and not of a clinical concern in 3/27 (11.1%) eyes, with a second procedure deemed necessary to alleviate symptoms in 5/27 (18.5%) eyes. All eyes treated with a second procedure had no recurrence of distichiae or symptoms. Complications following cryoepilation occurred in 4/27 (14.8%) eyes, with two cats developing bilateral entropion post-procedure. CONCLUSIONS: Treatment of distichiasis in cats utilizing cryoepilation was effective at alleviating symptoms, though some cats needed a second procedure. The development of post-procedural entropion was seen occasionally.

4.
Phys Rev Lett ; 120(9): 097401, 2018 Mar 02.
Article in English | MEDLINE | ID: mdl-29547302

ABSTRACT

We study exciton polaritons in a two-dimensional Lieb lattice of micropillars. The energy spectrum of the system features two flat bands formed from S and P_{x,y} photonic orbitals, into which we trigger bosonic condensation under high power excitation. The symmetry of the orbital wave functions combined with photonic spin-orbit coupling gives rise to emission patterns with pseudospin texture in the flat band condensates. Our Letter shows the potential of polariton lattices for emulating flat band Hamiltonians with spin-orbit coupling, orbital degrees of freedom, and interactions.

5.
J Occup Environ Hyg ; 12 Suppl 1: S69-81, 2015.
Article in English | MEDLINE | ID: mdl-26583908

ABSTRACT

Risk assessment forms the basis for both occupational health decision-making and the development of occupational exposure limits (OELs). Although genetic and epigenetic data have not been widely used in risk assessment and ultimately, standard setting, it is possible to envision such uses. A growing body of literature demonstrates that genetic and epigenetic factors condition biological responses to occupational and environmental hazards or serve as targets of them. This presentation addresses the considerations for using genetic and epigenetic information in risk assessments, provides guidance on using this information within the classic risk assessment paradigm, and describes a framework to organize thinking about such uses. The framework is a 4 × 4 matrix involving the risk assessment functions (hazard identification, dose-response modeling, exposure assessment, and risk characterization) on one axis and inherited and acquired genetic and epigenetic data on the other axis. The cells in the matrix identify how genetic and epigenetic data can be used for each risk assessment function. Generally, genetic and epigenetic data might be used as endpoints in hazard identification, as indicators of exposure, as effect modifiers in exposure assessment and dose-response modeling, as descriptors of mode of action, and to characterize toxicity pathways. Vast amounts of genetic and epigenetic data may be generated by high-throughput technologies. These data can be useful for assessing variability and reducing uncertainty in extrapolations, and they may serve as the foundation upon which identification of biological perturbations would lead to a new paradigm of toxicity pathway-based risk assessments.


Subject(s)
Epigenesis, Genetic , Hazardous Substances/toxicity , Occupational Exposure/standards , Occupational Health/standards , Gene-Environment Interaction , Genetics , Humans , Occupational Exposure/analysis , Polymorphism, Genetic , Risk Assessment , Toxicogenetics/methods
6.
J Occup Environ Hyg ; 12 Suppl 1: S7-17, 2015.
Article in English | MEDLINE | ID: mdl-26252067

ABSTRACT

Virtually no occupational exposure standards specify the level of risk for the prescribed exposure, and most occupational exposure limits are not based on quantitative risk assessment (QRA) at all. Wider use of QRA could improve understanding of occupational risks while increasing focus on identifying exposure concentrations conferring acceptably low levels of risk to workers. Exposure-response modeling between a defined hazard and the biological response of interest is necessary to provide a quantitative foundation for risk-based occupational exposure limits; and there has been considerable work devoted to establishing reliable methods quantifying the exposure-response relationship including methods of extrapolation below the observed responses. We review several exposure-response modeling methods available for QRA, and demonstrate their utility with simulated data sets.


Subject(s)
Occupational Exposure/history , Occupational Health/history , Risk Assessment/methods , Epidemiologic Methods , History, 20th Century , Humans , Models, Statistical , No-Observed-Adverse-Effect Level , Occupational Exposure/standards , Occupational Health/standards
8.
Oncogene ; 31(25): 3039-50, 2012 Jun 21.
Article in English | MEDLINE | ID: mdl-22020333

ABSTRACT

Glioblastoma multiforme (GBM) is an aggressive brain tumor for which there is no cure. Overexpression of wild-type epidermal growth factor receptor (EGFR) and loss of the tumor suppressor genes Ink4a/Arf and PTEN are salient features of this deadly cancer. Surprisingly, targeted inhibition of EGFR has been clinically disappointing, demonstrating an innate ability for GBM to develop resistance. Efforts at modeling GBM in mice using wild-type EGFR have proven unsuccessful to date, hampering endeavors at understanding molecular mechanisms of therapeutic resistance. Here, we describe a unique genetically engineered mouse model of EGFR-driven gliomagenesis that uses a somatic conditional overexpression and chronic activation of wild-type EGFR in cooperation with deletions in the Ink4a/Arf and PTEN genes in adult brains. Using this model, we establish that chronic activation of wild-type EGFR with a ligand is necessary for generating tumors with histopathological and molecular characteristics of GBMs. We show that these GBMs are resistant to EGFR kinase inhibition and we define this resistance molecularly. Inhibition of EGFR kinase activity using tyrosine kinase inhibitors in GBM tumor cells generates a cytostatic response characterized by a cell cycle arrest, which is accompanied by a substantial change in global gene expression levels. We demonstrate that an important component of this pattern is the transcriptional activation of the MET receptor tyrosine kinase and that pharmacological inhibition of MET overcomes the resistance to EGFR inhibition in these cells. These findings provide important new insights into mechanisms of resistance to EGFR inhibition and suggest that inhibition of multiple targets will be necessary to provide therapeutic benefit for GBM patients.


Subject(s)
Disease Models, Animal , ErbB Receptors/genetics , Glioblastoma/genetics , Mice , Proto-Oncogene Proteins c-met/genetics , Animals , ErbB Receptors/antagonists & inhibitors , Genes, Tumor Suppressor , Glioblastoma/physiopathology , Humans , Mice, Transgenic
9.
Vet Ophthalmol ; 13(3): 173-8, 2010 May.
Article in English | MEDLINE | ID: mdl-20500717

ABSTRACT

Repair of eyelid agenesis in nine eyes of five cats using a lip commissure to eyelid transposition is described. The procedure is a modification of the technique described by Pavletic for reconstruction of the canine inferior eyelid and provides skin, mucosa, a mucocutaneous junction, and muscle to reconstruct the superior and inferior eyelid and lateral canthus. The technique was successful in all eyes and resulted in improvement in corneal protection, cosmesis and in several cats a return of the palpebral reflex.


Subject(s)
Blepharoplasty/veterinary , Cat Diseases/congenital , Coloboma/veterinary , Eyelids/abnormalities , Surgical Flaps/veterinary , Animals , Blepharoplasty/methods , Cat Diseases/surgery , Cats , Coloboma/surgery , Eyelids/surgery , Female , Lip , Male , Ophthalmologic Surgical Procedures/methods , Ophthalmologic Surgical Procedures/veterinary
10.
Transplant Proc ; 36(10): 3239-41, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15686737

ABSTRACT

The current method for monitoring cyclosporine measures predose concentrations (C0). A better method has been developed, namely, measurement of the blood cyclosporine concentration at 2 hours postdose (C2). The aim of this survey was to determine the variability of C0 and C2 concentrations among stable renal transplant patients. One hundred two stable renal transplant patients who were at least 6 months posttransplant were recruited from the renal transplant outpatient clinic. The cyclosporine dose was between 100 and 500 mg daily; all patients had been monitored using C0 concentrations. Blood samples for cyclosporine concentration measurements were taken at both C0 and C2 at two consecutive clinic visits. The within- and between-patient variabilities were calculated using nested analysis of variance. The mean age was 50 years (21 to 81); the mean weight was 75 kg. The mean cyclosporine dose was 3.18 mg/kg/d (1.2 to 8.8). The average serum creatinine was 174 micromol/L (77 to 626) and the average cholesterol was 5 micromol/L (3 to 9). The mean (+/-SD) C0 concentration was 150 (47.31) microg/L and C2=895 (239) microg/L. The C0 concentration varied over 16-fold between patients compared to a sevenfold variation in C2. The between-subject coefficient of variation (CV) was 35% for C0 and 30% for C2 and the within subject CV was 23% for C0 and 20% for C2. The results suggest that cyclosporine concentrations at C0 are slightly more variable than those at C2. Whether this modest reduction in variability results in better patient outcomes is the subject of the next phase of this study.


Subject(s)
Cyclosporine/blood , Kidney Transplantation/physiology , Creatinine/blood , Cyclosporine/therapeutic use , Drug Monitoring/methods , Humans , Immunosuppressive Agents/blood , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Time Factors
11.
Bioorg Med Chem Lett ; 11(14): 1925-9, 2001 Jul 23.
Article in English | MEDLINE | ID: mdl-11459662

ABSTRACT

The lipophilic 1-substituent in a series of 1-((amidolinked)-alkyl)-pyrimidones, inhibitors of recombinant lipoprotein-associated phospholipase A(2), has been modified to give inhibitors of high potency in human plasma and enhanced physicochemical properties. Phenylpiperazineacetamide derivative 23 shows very promising oral activity.


Subject(s)
Enzyme Inhibitors/pharmacology , Phospholipases A/antagonists & inhibitors , Phospholipases A/blood , 1-Alkyl-2-acetylglycerophosphocholine Esterase , Administration, Oral , Animals , Enzyme Inhibitors/chemical synthesis , Humans , Inhibitory Concentration 50 , Metabolic Clearance Rate/physiology , Microsomes, Liver/metabolism , Piperazines/chemical synthesis , Piperazines/pharmacology , Pyrimidinones/chemical synthesis , Pyrimidinones/pharmacology , Rabbits , Rats
12.
Bioorg Med Chem Lett ; 11(5): 701-4, 2001 Mar 12.
Article in English | MEDLINE | ID: mdl-11266173

ABSTRACT

Modification of the pyrimidone 5-substituent in a series of 1-((amidolinked)-alkyl)-pyrimidones, lipophilic inhibitors of lipoprotein-associated phospholipase A2, has given inhibitors of nanomolar potency and improved physicochemical properties. Compound 23 was identified as a potent, highly water soluble. CNS penetrant inhibitor suitable for intravenous administration.


Subject(s)
Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Phospholipases A/antagonists & inhibitors , Pyrimidinones/chemistry , Pyrimidinones/pharmacology , Animals , Arteriosclerosis/drug therapy , Drug Administration Routes , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacokinetics , Humans , Male , Molecular Structure , Phospholipases A/metabolism , Phospholipases A2 , Pyrimidinones/chemical synthesis , Rabbits , Rats , Solubility , Water/chemistry
13.
EDTNA ERCA J ; 27(1): 28-30, 2001.
Article in English | MEDLINE | ID: mdl-12603070

ABSTRACT

Traditionally, the patient has relied on health care professionals for advice and knowledge. The unprecedented access to information offered by the Internet may challenge this relationship. To investigate this, a questionnaire was sent to 640 transplant patients. 24 responded positively and were interviewed to see if the information they found on the net had been useful, in negotiating a change in treatment or as support. Internet use was associated with younger males who had access to the net at work. 22 had found useful information although only 1 patient had negotiated a change in treatment as a result. As the Internet becomes universally available, patients will be empowered to have a larger role in maintaining their health, and support groups will be better able to help patients. To prepare to deal with this avalanche of information we need to develop a system of accreditation of Internet sites, to create our own sites and to collaborate with patient support groups.


Subject(s)
Internet/statistics & numerical data , Kidney Transplantation/nursing , Patient Participation , Adult , Europe , Female , Humans , Information Dissemination , Male , Quality of Health Care , Self-Help Groups , United States
14.
EDTNA ERCA J ; 27(2): 88-91, 2001.
Article in English | MEDLINE | ID: mdl-11868756

ABSTRACT

This unit carried out 29 live donor transplants over a 3-year period. Many potential donors did not proceed to transplant. For those who had an acceptable tissue type, were blood group compatible and lymphocytotoxic crossmatch negative, we looked at the reasons for cancelling the donor work up. The reasons were impaired renal function (5 potential donors), cardiac/hypertension (4 potential donors), renovascular (1 potential donor), cancer (1 potential donor), cross-match positive at a late stage (3 potential donors), failure to attend at clinic/change of mind (6 potential donors) and hepatitis (2 potential donors). Improvements carried out following the audit include a list of tests which potential donors living away from this unit--especially those abroad--are asked to do before travelling here. An information leaflet has also been produced for potential donors.


Subject(s)
Kidney Transplantation , Living Donors , Humans , Kidney Transplantation/nursing , Living Donors/supply & distribution , Patient Selection , Tissue and Organ Procurement/statistics & numerical data , United Kingdom
15.
Bioorg Med Chem Lett ; 10(22): 2557-61, 2000 Nov 20.
Article in English | MEDLINE | ID: mdl-11086729

ABSTRACT

From two related series of 2-(alkylthio)-pyrimidones, a novel series of 1-((amidolinked)-alkyl)-pyrimidones has been designed as nanomolar inhibitors of human lipoprotein-associated phospholipase A2. These compounds show greatly enhanced activity in isolated plasma. Selected derivatives such as compounds 51 and 52 are orally active with a good duration of action.


Subject(s)
Enzyme Inhibitors/pharmacology , Lipoproteins/metabolism , Phospholipases A/antagonists & inhibitors , Pyrimidinones/pharmacology , Administration, Oral , Animals , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/chemistry , Molecular Structure , Phospholipases A/metabolism , Phospholipases A2 , Pyrimidinones/administration & dosage , Pyrimidinones/chemistry , Rabbits
16.
J Immunol ; 165(8): 4667-75, 2000 Oct 15.
Article in English | MEDLINE | ID: mdl-11035110

ABSTRACT

Mice chimeric for integrins alpha(5), alpha(V), or alpha(4) were used to dissect the in vivo roles of these adhesion receptors during leukocyte development and traffic. No major defects were observed in the development of lymphocytes, monocytes, or granulocytes or in the traffic of lymphocytes to different lymphoid organs in the absence of alpha(5) or alpha(V) integrins. However, in agreement with previous reports, the absence of alpha(4) integrins produced major defects in development of lymphoid and myeloid lineages and a specific defect in homing of lymphocytes to Peyer's patches. In contrast, the alpha(4) integrin subunit is not essential for localization of T lymphocytes into intraepithelial and lamina propria compartments in the gut, whereas one of the partners of alpha(4), the beta(7) chain, has been shown to be essential. However, alpha(4)-deficient T lymphocytes cannot migrate properly during the inflammatory response induced by thioglycolate injection into the peritoneum. Finally, in vitro proliferation and activation of lymphocytes deficient for alpha(5), alpha(V), or alpha(4) integrins upon stimulation with different stimuli were similar to those seen in controls. These results show that integrins play distinct roles during in vivo leukocyte development and traffic.


Subject(s)
Cell Movement/immunology , Chimera/immunology , Integrins/physiology , Leukocytes/cytology , Leukocytes/immunology , Animals , Antigens, CD/genetics , Antigens, CD/physiology , Cell Division/genetics , Cell Division/immunology , Cell Movement/genetics , Integrin alpha4 , Integrin alpha5 , Integrin alphaV , Integrins/genetics , Lymphocyte Activation/genetics , Lymphocytes/cytology , Lymphocytes/immunology , Mice , Mice, Inbred C57BL , Mice, Knockout , Myeloid Cells/immunology , Peritonitis/chemically induced , Peritonitis/genetics , Peritonitis/immunology , Receptors, Lymphocyte Homing/physiology , Thioglycolates/administration & dosage
17.
EDTNA ERCA J ; 26(1): 26-8, 2000.
Article in English | MEDLINE | ID: mdl-11011632

ABSTRACT

The transplant waiting list needs to be actively managed by the transplant centre in a systematic way to achieve any degree of efficiency and effectiveness. This paper describes the key role of the transplant nurse in a large centre with over 300 people on the transplant waiting list. It focuses on the way patients are assessed, how the list is updated and the benefit of nurse involvement in the work-up of potential live donors.


Subject(s)
Kidney Transplantation/nursing , Living Donors , Patient Selection , Preoperative Care/methods , Tissue and Organ Procurement/methods , Waiting Lists , Humans , Kidney Failure, Chronic/surgery , Nursing Assessment
18.
Laryngoscope ; 110(7): 1225-9, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10892701

ABSTRACT

OBJECTIVES: In the management of two related patients with multicentric glomus jugulare tumors, given the incidence of 1:30,000 with approximately 20% familial cases, our objective was to review the genetic characteristics and inheritance patterns of these tumors and to determine what molecular genetic screening possibilities exist for the phenotypically normal family members. In addition, our aim was to review the incidence of various multicentric paraganglioma (PGL) tumor location combinations. METHODS: Molecular genetic linkage analysis testing was performed on the 2 patients and 14 other unaffected family members. We report the results of this screening and review the literature on the incidence and genetics of paragangliomas. RESULTS: The inheritance pattern in the literature demonstrates autosomal dominant transmission with maternal imprinting (inactivation). The proclivity for multicentric origin increases to 26% in familial cases, as reflected in our patients. In addition to the two patients, four unaffected family members demonstrated the presence of the disease haplotype at chromosome band 11q23, which indicates a very high likelihood of developing a paraganglioma, given the highly penetrant nature of the disease. CONCLUSIONS: It is clear that the familial PGL gene locus is situated at chromosome 11q23. The gene itself and its exact degree of penetrance, however, still await identification. Since early detection of paragangliomas reduces the incidence of morbidity and mortality, genotypic analysis as a screening tool in families of affected patients should play a front-line diagnostic role, leading to more timely and cost-effective patient management.


Subject(s)
Glomus Jugulare Tumor/diagnosis , Glomus Jugulare Tumor/genetics , Paraganglioma/diagnosis , Paraganglioma/genetics , Chromosomes, Human, Pair 11/genetics , Gene Expression/genetics , Genetic Linkage , Haplotypes/genetics , Humans
19.
Infect Immun ; 67(5): 2464-74, 1999 May.
Article in English | MEDLINE | ID: mdl-10225909

ABSTRACT

Most human oral viridans streptococci participate in intrageneric coaggregations, the cell-to-cell adherence among genetically distinct streptococci. Two genes relevant to these intrageneric coaggregations were identified by transposon Tn916 mutagenesis of Streptococcus gordonii DL1 (Challis). A 626-bp sequence flanking the left end of the transposon was homologous to dltA and dltB of Lactobacillus rhamnosus ATCC 7469 (formerly called Lactobacillus casei). A 60-kb probe based on this flanking sequence was used to identify the homologous DNA in a fosmid library of S. gordonii DL1. This DNA encoded D-alanine-D-alanyl carrier protein ligase that was expressed in Escherichia coli from the fosmid clone. The cloned streptococcal dltA was disrupted by inserting an ermAM cassette, and then it was linearized and transformed into S. gordonii DL1 for allelic replacement. Erythromycin-resistant transformants containing a single insertion in dltA exhibited a loss of D-alanyl esters in lipoteichoic acid (LTA) and a loss of intrageneric coaggregation. This phenotype was correlated with the loss of a 100-kDa surface protein reported previously to be involved in mediating intrageneric coaggregation (C. J. Whittaker, D. L. Clemans, and P. E. Kolenbrander, Infect. Immun. 64:4137-4142, 1996). The mutants retained the parental ability to participate in intergeneric coaggregation with human oral actinomyces, indicating the specificity of the mutation in altering intrageneric coaggregations. The mutants were altered morphologically and exhibited aberrant cell septa in a variety of pleomorphs. The natural DNA transformation frequency was reduced 10-fold in these mutants. Southern analysis of chromosomal DNAs from various streptococcal species with the dltA probe revealed the presence of this gene in most viridans streptococci. Thus, it is hypothesized that D-alanyl LTA may provide binding sites for the putative 100-kDa adhesin and scaffolding for the proper presentation of this adhesin to mediate intrageneric coaggregation.


Subject(s)
Bacterial Adhesion/genetics , Bacterial Adhesion/physiology , Genes, Bacterial , Streptococcus/genetics , Streptococcus/metabolism , Teichoic Acids/biosynthesis , Adhesins, Bacterial/genetics , Adhesins, Bacterial/metabolism , Amino Acid Sequence , Base Sequence , Cloning, Molecular , DNA Primers/genetics , DNA Transposable Elements/genetics , DNA, Bacterial/genetics , Humans , Microscopy, Electron , Microscopy, Electron, Scanning , Molecular Sequence Data , Mouth/microbiology , Mutagenesis, Insertional , Sequence Homology, Amino Acid , Streptococcus/ultrastructure
20.
J Mol Biol ; 286(5): 1461-9, 1999 Mar 12.
Article in English | MEDLINE | ID: mdl-10064709

ABSTRACT

We introduce a generally applicable method for the discovery and quantitation of all of the characteristic statistical properties of a class of biological sequences, given examples from the class. This method employs a reversible binary encoding of sequences into the binary digits -1 and +1. Then, provided that the sample is sufficient, the sample cumulants on the subsets of digit positions will manifest all of the statistical properties of the class. As an illustration, we present the main results of a complete characterization of the stationary statistical properties of human coding sequences, in terms of their sample cumulants. Many of the telling sample cumulants are described.


Subject(s)
Codon/genetics , DNA/classification , DNA/genetics , Models, Genetic , Base Sequence , Databases, Factual , Genetic Code , Humans , Molecular Sequence Data , Pattern Recognition, Automated , Proteins/classification , Proteins/genetics , Statistics as Topic
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