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Biomedical subjects

L Kan

Publications and source records attributed to L Kan.

At least 19 recordsLinked to original sources
PubMed2003

Risk of invasive cervical cancer after three consecutive negative Pap smears.

OBJECTIVES: To determine the factors that influence risk of cervical cancer after three consecutive negative Pap smears. METHODS: A cohort study was conducted using data from the British Columbia Cervical Cancer Screening Program and British Columbia Cancer Registry. Analysis was based on a one percent sample of women aged 20-69 years with Pap smears enriched with all invasive cervical cancer cases diagnosed between 1994-99. Screening intervals, after three negative screens, were created with the following variables: age at beginning of interval, interval length, previous cytologic abnormality and previous cervical procedure. The risk of cervical cancer by histologic type was calculated using survival analysis methods. RESULTS: The sample consisted of 10,509 women, who contributed 28,309 intervals, and 371 cervical cancer cases. The incidence rate of invasive squamous cervical cancer increased with time since last screen up to six years. Women with a history of dysplasia remained at elevated risk for squamous cancer, hazard ratio=2.6 (95% confidence interval [CI]=1.9, 3.4) but age or previous procedure were not related to risk. No relationship between time since last screen and non-squamous cancer risk was found although history of a previous procedure was significant. The marginal effectiveness of Pap smears declined with increasing frequency of use. CONCLUSIONS: This study confirmed the preventive effect of Pap smear screening and its dependency on frequency of use. Women with a history of dysplasia, prior to three consecutive negatives, were at increased risk of developing invasive squamous cervical cancer compared with women with no such history.

Adult↗
PubMed2001

Waiting times from abnormal breast screen to diagnosis in 7 Canadian provinces.

BACKGROUND: Delay to breast cancer diagnosis following an abnormal screening result is associated with anxiety and personal disruption. We assessed the patterns and timeliness of diagnostic follow-up after breast cancer screening for women with abnormal results who attended organized screening programs in 7 provinces. METHODS: Using data from the Canadian Breast Cancer Screening Database, we identified 203,141 women aged 50-69 years who underwent screening in 1996 through provincially organized breast cancer screening programs in British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Nova Scotia and Newfoundland. We prospectively followed women with an abnormal screening result through to the completion of the assessment process. We evaluated the waiting times from screening examination to first assessment, from screening examination to first imaging, from screening examination to diagnosis and from first assessment to diagnosis for 13,958 women, stratified according to screening program, mode of detection, whether a biopsy was performed and whether cancer was diagnosed. RESULTS: We observed considerable variations between and within programs in the time to diagnosis. The median time from screening examination to first assessment was 2.6 weeks. The median time from screening examination to diagnosis was 3.7 weeks; this time increased to 6.9 weeks for women undergoing biopsy. Even when no biopsy was performed, 10% of the women waited 9.6 weeks or longer for a diagnosis, as compared with 15.0 weeks or longer for 10% of the women undergoing biopsy. Among the women who had a biopsy, the use of core biopsy was associated with a shorter median time to diagnosis than was open biopsy, and those found to have cancer had shorter waiting times than women with benign biopsy findings. INTERPRETATION: Women undergoing assessment of an abnormal breast cancer screening result waited many weeks for a diagnosis, especially when a biopsy was performed. To ensure that targets for timeliness, adopted nationally in 1999, are realized, improved models of care or dissemination of existing efficient techniques to reach a diagnosis will be needed.

Aged↗
PubMed2001

Polyproline II helix is a key structural motif of the elastic PEVK segment of titin.

Titin is a family of giant elastic proteins that constitute an elastic sarcomere matrix in striated muscle. In the I-band region of the sarcomere, where titin extends and develops passive force upon stretch, titin is composed of tandem repeats of approximately 100 residue immunoglobin domains and approximately 28-residue PEVK modules. We have performed 2D NMR and circular dichroism (CD) studies of the conformations of one representative 28-mer PEVK module from human fetal titin (PEPPKEVVPEKKAPVAPPKKPEVPPVKV). NMR data of synthetic peptides of this module as well as three constituent peptides of 9 to 12 residues in aqueous solutions reveal distinguishing features for left-handed three-residue per turn PPII helices: the lack of NOE NN(i, i+1), very large NOE alphaN(i, i+1)/NN(i, i+1), no medium range NOE alphaN(i, i+2), and dihedral angles phi and psi values of -78 and 146, respectively. Structural determinations indicate the presence of three short stretches of PPII helices of 4, 5, and 6 residues that are interposed with an unordered, and presumably flexible, spacer region to give one "polyproline II helix-coil" or "PhC" motif for roughly every 10 residues. These peptides also display the characteristic PPII CD spectra: positive peak or negative shoulder band at 223 nm, negative CD band near 200 nm, and biphasic thermal titration curves that reflect varied stability of these PPII helices. We propose that this PhC motif is a fundamental feature and that the number, length, stability, and distribution of PPII is important in the understanding of the elasticity and protein interactions of the PEVK region of titin.

Amino Acid Motifs↗
PubMed2001

Localization and density of myeloid leucocytes in the periodontal ligament of normal rat molars.

The phenotypic distribution and density of macrophage-associated antigen-expressing cells in the periodontal ligament (PDL) of normal rat mandibular first molars was evaluated by immunohistochemistry, and an attempt made to identify dendritic cells (DCs) by immunoelectron microscopy. Cells immunopositive to ED1 (a general macrophage marker) were widely distributed throughout the PDL and were most common around blood vessels. A small number of T lymphocytes and OX62 (anti-veiled cells and gammadelta T cells)-positive DC-like cells were also found. The relative density of cells immunopositive to ED9 (CD14), OX42 (CD11b), OX6 (anti-class II MHC molecules), ED2 (anti-tissue-resident macrophages), 8A2 (CD11c) and WT.1 (CD11a) varied in the mesial, distal and periapical regions of the distal root and the furcal region. This finding suggests that there are several subpopulations of ED1-positive cells which express various combinations of these markers. Immunoelectron microscopy revealed that a small, but distinct, subpopulation of ED1- and OX6-positive cells did have a DC-like ultrastructure, although the majority of these cells were identified as macrophages. The DC-like cells were characterized by poorly developed lysosomal structures and an absence of phagocytic vesicles. It was concluded that the normal rat PDL is equipped with heterogeneous populations of macrophages with regional variations in density. The DC-like cells may function as antigen-presenting cells.

Animals↗
PubMed2001

An immunoelectron-microscopic study of class II major histocompatibility complex molecule-expressing macrophages and dendritic cells in experimental rat periapical lesions.

Previous studies have demonstrated that heterogeneous populations of class II major histocompatibility complex (MHC) molecule-expressing non-lymphoid cells, ultrastructurally classified as macrophages and dendritic cell (DC) cell-like cells, comprise the major immune cell population in experimental periapical lesions in rat molars. In this study, the temporal changes in relative proportions of the two types of cells were examined, on the hypothesis that they are involved in different aspects of the pathogenesis of the lesions. The lesions were induced by making surgical pulp exposures in mandibular first molars of 5-week-old Wistar rats. Observation periods were set at 0 (normal), 3, 14, 28, and 56 days. Non-lymphoid cells immunoreactive to OX6 (reactive to class II MHC molecules) were classified as macrophages and DC cell-like cells according to their ultrastructure, and the frequencies of the two types of cells were assessed at each time-point. ED1 (reactive to nearly all macrophages and DCs) was also used to identify macrophages and DC cell-like cells. At 3 days, most OX6+ cells and ED1+ cells in the periapical tissue had the ultrastructural appearance of newly recruited macrophages. At 14 days, when the lesion was actively expanding, there were significantly more OX6+ macrophages than OX6+ DC cell-like cells (P<0.01). However, at 28 days, when lesion expansion had ceased, DC cell-like cells significantly outnumbered OX6+ macrophages (P<0.01); this remained constant at 56 days. Cell-to-cell contact between OX6+ non-lymphoid cells and OX6- lymphocytes, suggesting a functional interaction, was most frequently seen at 28 days. These results support the notion that class II MHC molecule-expressing macrophages play some part in the initial lesion expansion, and suggest that DC cell-like cells may primarily be involved in immune defence against perpetuated antigenic challenges following lesion stabilization.

Animals↗
PubMed2001

The T lymphocyte structure CD60 contains a sialylated carbohydrate epitope that is expressed on both gangliosides and glycoproteins.

The CD60 antigen is expressed on a majority of T cells in autoimmune lesions, and anti-CD60 can activate T lymphocytes. CD60 has been defined as the GD3 ganglioside, and subsequently as the 9-O-acetylated form of GD3. However, other evidence suggests that anti-CD60 recognizes a glycoprotein or family of glycoproteins expressed by T lymphocytes. The current studies were undertaken to better define the identity of the CD60 antigen on both T cells and non-T cells. Treatment of intact cells with neuraminidases of various specificities confirmed that detection of the CD60 epitope depends on expression of an alpha2, 8-disialic acid carbohydrate linkage, as is found in GD3 and related gangliosides. However, the sialicacid polymer colominic acid inhibited anti-GD2 and anti-GD3, but not anti-CD60 from binding to cell surfaces. Expression of CD60 did not correlate with expression of GD3 on a variety of cell lines and T cell populations. Expression of CD60 and 9-O-acetyl-GD3 was roughly parallel on some non-T cell lines such as melanoma cells, but on T cells expression of CD60 was consistently greater. Antibodies to GD2, GD3 and 9-O-acetyl-GD3 were ineffective at inhibiting binding of anti-CD60 to CD60+ cells. Activation responses of T cells to anti-CD60 were inducible in either the presence or absence of a response to anti-GD3. A novel inhibitor of glucosyl ceramide synthesis, D-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (D-t-P4) reduced expression of GD3 much more than CD60 on activated T lymphocytes. Following biotinylation of HUT78 T cells, anti-CD60 immunoprecipitated a 70 kDa antigen. Taken together, the present data and previous findings suggest that anti-CD60 can recognize both a modified form of the GD3 ganglioside and a carbohydrate-dependent complex epitope present on one or more glycoproteins. This glycoprotein epitope may be the more abundant and functionally significant CD60 antigen on T lymphocytes, while 9-O-acetyl-GD3 is likely to be the principal structure recognized by anti-CD60 on melanoma cells. These findings emphasize the complexity of understanding the functional roles of carbohydrate epitopes in cell activation.

Antigens, CD↗
PubMed2001

Ultrastructural analysis of MHC class II molecule-expressing cells in experimentally induced periapical lesions in the rat.

Periapical lesions were induced by making 28 days of unsealed pulp exposures in the lower first molars of Wistar rats. Major histocompatibility complex class II molecule-expressing cells were then demonstrated by means of immunoperoxidase staining using a monoclonal antibody OX6, and the ultrastructure of these cells was analyzed under electron microscopy. OX6+ cells were classified into two major populations, (i.e. macrophages and dendritic cell (DC)-like cells. DC-like cells had elongated cytoplasmic processes, contained a few lysosomal structures, lacked distinct phagosomes, and were the most predominant cell type in the established lesion. Some of lymphocytes and plasma cells also showed a positive immunoreactivity. Both OX6+ macrophages and DC-like cells often showed a cell-to-cell attachment with lymphocytes. These findings suggested that major histocompatibility complex class 11 molecule-expressing macrophages and DC-like cells may play a crucial role in periapical lesion development by acting as antigen-presenting cells to memory T lymphocytes.

Animals↗
PubMed2000

Isolation and characterization of peroxisome proliferator-activated receptor (PPAR) interacting protein (PRIP) as a coactivator for PPAR.

We previously isolated and identified steroid receptor coactivator-1 (SRC-1) and peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP/PPARBP) as coactivators for PPAR, using the ligand-binding domain of PPARgamma as bait in a yeast two-hybrid screening. As part of our continuing effort to identify cofactors that influence the transcriptional activity of PPARs, we now report the isolation of a novel coactivator from mouse, designated PRIP (peroxisome proliferator-activated receptor interacting protein), a nuclear protein with 2068 amino acids and encoded by 13 exons. Northern analysis showed that PRIP mRNA is ubiquitously expressed in many tissues of adult mice. PRIP contains two LXXLL signature motifs. The amino-terminal LXXLL motif (amino acid position 892 to 896) of PRIP was found to be necessary for nuclear receptor interaction, but the second LXXLL motif (amino acid position 1496 to 1500) appeared unable to bind PPARgamma. Deletion of the last 12 amino acids from the carboxyl terminus of PPARgamma resulted in the abolition of the interaction between PRIP and PPARgamma. PRIP also binds to PPARalpha, RARalpha, RXRalpha, ER, and TRbeta1, and this binding is increased in the presence of specific ligands. PRIP acts as a strong coactivator for PPARgamma in the yeast and also potentiates the transcriptional activities of PPARgamma and RXRalpha in mammalian cells. A truncated form of PRIP (amino acids 786-1132) acts as a dominant-negative repressor, suggesting that PRIP is a genuine coactivator.

Amino Acid Sequence↗
PubMed2000

Headaches in a pediatric emergency department: etiology, imaging, and treatment.

OBJECTIVE: To assess the spectrum of diagnoses, the use of CT scans of the brain, and pharmacological treatments in patients presenting to a pediatric emergency department with headaches as the chief complaint. METHODS: A 1-year retrospective chart review of all children who presented to the emergency department with a headache as the chief complaint. RESULTS: One hundred thirty patients (0.7% of all pediatric emergency department visits, mean age = 9.3 years) were included in the study. Primary headaches included 11 migraine (8.5%) and 2 tension headaches (1.5%). Most of the secondary nonneurological headaches were associated with viral and respiratory illnesses (n=37, 28.5%), while the majority of the secondary neurological headaches included 26 posttraumatic (20%), 15 possible ventriculoperitoneal shunt malfunctions (11.5%), and 3 cases of aseptic meningitis (2.3%). The neurological etiology in 9 of these children (6.9%) was found to be serious (subdural hematoma, epidural hematoma, proven ventriculoperitoneal shunt malfunction, brain abscess, pseudotumor cerebri, and aseptic meningitis). Fifteen patients could not be etiologically classified, either because no specific etiology was found or their discharge diagnoses could not clearly explain the headache. Approximately 10% (5/53) of the CT scans of the head that were performed showed new abnormal findings including hydrocephalus secondary to ventriculoperitoneal shunt malfunction (2), subdural hematoma (1), epidural hematoma (1), and skull fracture (1). Forty-two patients (32%) were treated pharmacologically. Thirty-nine of the 42 treated patients (93%) were given over-the-counter analgesics, and 9 (21%) were given prescribed analgesics. CONCLUSIONS: The majority of the headaches in the pediatric emergency department were secondary to concurrent illness and minor head trauma, and required no pharmacological treatment or only treatment with minor analgesics. In a small minority of patients, headaches were secondary to serious neurological conditions, which required immediate medical attention. Computed tomography scans showed new abnormalities in a minority of patients and should be reserved for those with neurological diagnoses such as head trauma and ventriculoperitoneal shunt, as well as for those patients with recent onset of headaches with no clear etiological explanation, and for those with high-risk medical conditions, such as hypocoagulabilities. Future prospective studies are needed to assess the efficacy of the various pharmacological treatments in this population.

Adolescent↗
PubMed2000

Ten years of breast screening in the Screening Mammography Program of British Columbia, 1988-97.

OBJECTIVES: To evaluate 10 years outcomes of the Screening Mammography Program of British Columbia (SMPBC) and determine if breast screening targets were being achieved among women aged 40-80+ years. SETTING: Organised breast screening programme in British Columbia, Canada. METHODS: Rates of participation, abnormal referral, cancer detection, and interval cancer were calculated for asymptomatic women receiving an SMPBC mammography from 1988-97. RESULTS: 895,849 screening mammographies were provided to 335,433 women. 51.3% of women were age 50-69 years. Abnormalities were identified on 57,454 screens (6.4%) from which 3304 cancers were detected. Abnormal call rates were higher on first (9.8%), compared with subsequent screens (4.4%) and declined with age: 7.7% at age < 40 to 5.4% for age 70-79 years. Cancer detection rates were higher on first (5.0 per 1000) compared with subsequent screens (2.8 per 1000) and increased smoothly with age from 1.4 to 8.2 per 1000 from age < 40 to age 80 years and older. Twenty per cent of cancers were non-invasive. The median size of invasive cancers was 14 mm and 81% had no axillary lymph node metastases. The 12 month interval cancer rate was 0.6 per 1000 and did not vary significantly with age or screening history. The prevalence to expected incidence ratio was 3.1 for women age 50-79 years. CONCLUSION: Across a broad range of ages, surrogate indices of screening mammography success have been achieved in a population based, North American, organised breast cancer screening programme.

Adult↗
PubMed2000

Standardized abnormal interpretation and cancer detection ratios to assess reading volume and reader performance in a breast screening program.

PURPOSE: To determine the relationship between annual screening volume and radiologist performance in the Screening Mammography Program of British Columbia, Canada. MATERIALS AND METHODS: Standardized abnormal interpretation ratios and standardized cancer detection ratios were constructed for 35 readers with at least 3 years of experience with the Screening Mammography Program of British Columbia. The ratios were used to compare individual reader performance with the mean program performance after adjustment for the age and screening history (first versus subsequent screening examinations) of the women who underwent screening. RESULTS: The mean standardized abnormal interpretation ratio was better for readers of 2,000-2,999 (n = 8) and 3,000-3,999 (n = 9) screening mammograms per year than for those of less than 2,000 (n = 9) and 4, 000-5,199 (n = 9) screening mammograms per year. Differences in the mean standardized abnormal interpretation ratios were significant (P <.05) between the readers of less than 2,000 and of 2,000-2,999 screening mammograms per year, between readers of less than 2,000 and of 3,000-3,999 screening mammograms per year and between readers of 3,000-3,999 and of 4,000-5,199 screening mammograms per year. The mean standardized cancer detection ratio improved gradually with increasing annual volume, but the differences between groups were not statistically significant. Five of the eight readers of 2,000-2, 999 mammograms were reading 2,475 or more screening mammograms per year. CONCLUSION: Standardized abnormal interpretation ratios and standardized cancer detection ratios provide a method of comparing two important performance measures in a screening program. A minimum of 2,500 interpretations per year is associated with lower abnormal interpretation rates and average or better cancer detection rates.

Adult↗
PubMed1999

Haloalkane dehalogenases: structure of a Rhodococcus enzyme.

The hydrolytic haloalkane dehalogenases are promising bioremediation and biocatalytic agents. Two general classes of dehalogenases have been reported from Xanthobacter and Rhodococcus. While these enzymes share 30% amino acid sequence identity, they have significantly different substrate specificities and halide-binding properties. We report the 1.5 A resolution crystal structure of the Rhodococcus dehalogenase at pH 5.5, pH 7.0, and pH 5.5 in the presence of NaI. The Rhodococcus and Xanthobacter enzymes have significant structural homology in the alpha/beta hydrolase core, but differ considerably in the cap domain. Consistent with its broad specificity for primary, secondary, and cyclic haloalkanes, the Rhodococcus enzyme has a substantially larger active site cavity. Significantly, the Rhodococcus dehalogenase has a different catalytic triad topology than the Xanthobacter enzyme. In the Xanthobacter dehalogenase, the third carboxylate functionality in the triad is provided by D260, which is positioned on the loop between beta7 and the penultimate helix. The carboxylate functionality in the Rhodococcus catalytic triad is donated from E141. A model of the enzyme cocrystallized with sodium iodide shows two iodide binding sites; one that defines the normal substrate and product-binding site and a second within the active site region. In the substrate and product complexes, the halogen binds to the Xanthobacter enzyme via hydrogen bonds with the N(eta)H of both W125 and W175. The Rhodococcusenzyme does not have a tryptophan analogous to W175. Instead, bound halide is stabilized with hydrogen bonds to the N(eta)H of W118 and to N(delta)H of N52. It appears that when cocrystallized with NaI the Rhodococcus enzyme has a rare stable S-I covalent bond to S(gamma) of C187.

Amino Acid Sequence↗
PubMed1999

Screening Mammography Program of British Columbia: pattern of use and health care system costs.

BACKGROUND: The use of mammography for screening asymptomatic women has increased dramatically in the past decade. This report describes the changes that have occurred in the use of bilateral mammography in British Columbia since the provincial breast cancer screening program began in 1988. METHODS: Using province-wide databases from both the breast cancer screening program and the provincial health insurance plan in BC, the authors determined the number and costs of bilateral mammography services for women aged 40 years or older between Apr. 1, 1986, and Mar. 31, 1997. Unilateral mammography was excluded because it is used for investigating symptomatic disease and screening abnormalities, and for follow-up of women who have undergone mastectomy for cancer. RESULTS: As the provincial breast cancer screening program expanded from 1 site in 1988 to 23 in 1997, it provided an increasing proportion of the bilateral mammographic examinations carried out each year in BC. In fiscal year 1996/97, 65% of bilateral mammographic examinations were performed through the screening program. The cost per examination within the screening program dropped as volume increased. Thirty percent more bilateral mammography examinations were done in 1996/97 than in 1991/92, but health care system expenditures for these services increased by only 4% during the same period. In calendar year 1996, 21% of new breast cancers were diagnosed as a result of a screening program visit. INTERPRETATION: Substantial increases in health care expenditures have been avoided by shifting bilateral mammography services to the provincial screening program, which has a lower cost per screening visit.

Adult↗
PubMed1999

Prognosis, treatment, and recurrence of breast cancer for women attending or not attending the Screening Mammography Program of British Columbia.

Breast cancer screening programs have been initiated in many countries in the past decade. To determine the impact of the Screening Mammography Program of British Columbia (SMPBC), disease and treatment outcomes for women with breast cancer diagnosed in BC between 1989 and 1996 were compared on the basis of attendance at the SMPBC. An SMPBC attender was a women diagnosed with breast cancer within three years of an SMPBC screen, regardless whether the cancer was detected as a result of that screen. Of the 13,636 women aged 40-89 years diagnosed with breast cancer in BC during the study period, 2,647 (19.4%) were SMPBC attenders. 73.5% of SMPBC attenders (N = 1,946) and 74.2% of non-attenders (N = 8,149) were referred to the BC Cancer Agency and had pathology, staging, treatment, and outcome information available. SMPBC attenders compared with non-attenders were more likely to have in situ disease alone, and those with invasive cancers had smaller tumors which were less likely to have grade III histology and less likely to have spread to axillary lymph nodes (all P < 0.001). SMPBC attenders were more likely to be treated with breast conservation and less likely to receive adjuvant chemotherapy or tamoxifen (P < 0.001). Log-rank tests showed local (P = 0.017), distant (P < 0.001), and overall (P < 0.001) disease-free survival were better for SMPBC attenders. These favorable surrogate endpoints suggest that the benefits of breast screening as demonstrated by randomized trials can be translated into community practice by an organized breast screening program.

Adult↗
PubMed1999

Cloning and expression of the mouse deoxyuridine triphosphate nucleotidohydrolase gene: differs from the rat enzyme in that it lacks nuclear receptor interacting LXXLL motif.

We have previously reported the cloning of rat deoxyuridine triphosphate nucleotidohydrolase (dUTPase) cDNA and demonstrated that the full-length protein as well as the N-terminal 62-amino acid peptide interacts with peroxisome proliferator-activated receptor alpha (PPARalpha). We now report the cloning of mouse dUTPase cDNA and show that it contains a 162-amino acid open reading frame, encoding a protein with a predicted Mr of 17,400 and differs from rat cDNA, which contains additional 43 amino acids at the N-terminal end. Unlike rat dUTPase, mouse dUTPase failed to bind PPARalpha. An evaluation of 205 amino acid containing rat dUTPase cDNA revealed that the N-terminal 43 extra amino acid segment contains an LXXLL signature motif, considered necessary and sufficient for the binding of several cofactors with nuclear receptors, and its absence in murine dUTPase possibly accounts for the differential binding of these enzymes to PPARalpha. In situ hybridization and immunohistochemical studies revealed that, in the adult mouse, dUTPase is expressed at high levels in proliferating cells of colonic mucosa, and of germinal epithelium in testis. At 9.5-day mouse embryonic development, dUTPase expression is predominantly in developing neural epithelium, and hepatic primordium, and in later developmental stages (11.5-, 13.5-, and 15.5-day embryo), the expression began to be localized to the liver, kidney, gut epithelium, thymus, granular layer of the cerebellum, and olfactory epithelium. We also show that the murine dUTPase gene comprises 6 exons and the 5'-flanking region of -1479 to -27, which exhibited high promoter activity, contains a typical TATA box and multiple cis-elements such as Sp-1, AP2, AP3, AP4, Ker1, RREB, and CREB binding sites. These observations suggest the existence of variants of dUTPase, some of which may influence nuclear receptor function during development and differentiation, in addition to catalyzing the hydrolysis of dUTP to dUMP.

Amino Acid Sequence↗
PubMed1998

Change of thermal stability of colicin E7 triggered by acidic pH suggests the existence of unfolded intermediate during the membrane-translocation phase.

Purified colicin E7 was analyzed by CD spectrum and gel filtration chromatography in a mimicking membrane-translocation phase. It was found that the CD spectra of colicin E7 at pH 7 and pH 2.5 were similar. Although the melting temperature of the protein shifted from 54.5 degrees C to 34 degrees C at low pH, the thermal denaturation curves of colicin E7 at different pH conditions still fit a two-state model. These experimental results imply that a minor structural change, triggered by acidic pH, for instance, may reduce the energy required for protein melting. In contrast to the minor change in secondary structure at different pH conditions, we observed that, in vitro, all monomeric colicin E7s converted into multimer-like conformations after recovering from the partial unfolding process. This multimeric form of colicin can only be dissociated by formamide and guanidine hydrochloride, indicating that this protein complex is indeed formed by aggregation of the monomeric colicins. Most interestingly, the aggregated colicins still perform in vivo bacteriocidal activity. We suggest that in a partial unfolding state the colicin is prepared for binding to the specific targets for translocation through the membrane. However, in the absence of specific targets in vitro these unfold intermediates may therefore aggregate into the multimeric form of colicins.

Bacterial Proteins↗
PubMed1998

Pseudotumor cerebri in Lyme disease: a case report and literature review.

Pseudotumor cerebri is an unusual presentation of Lyme disease. The case of an 8-year-old girl with pseudotumor cerebri secondary to acute neuroborreliosis is reported. She presented with acute onset of headache, papilledema, sixth nerve palsy, increased intracranial pressure, and cerebrospinal fluid pleocytosis. Serum and cerebrospinal fluid Lyme antibodies were positive. Twelve reported cases that mostly presented with systemic findings and signs of Lyme disease before development of pseudotumor cerebri were reviewed. We conclude that acute neuroborreliosis can present with pseudotumor cerebri as an initial manifestation. It is important to include Lyme disease in the differential diagnosis of pseudotumor cerebri in an area endemic for Lyme disease.

Abducens Nerve↗