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Biomedical subjects

C L Phillips

Publications and source records attributed to C L Phillips.

At least 19 recordsLinked to original sources
PubMed2001

Three-dimensional imaging of embryonic mouse kidney by two-photon microscopy.

Developing mammalian embryonic kidney becomes progressively more elaborate as the ureteric bud branches into undifferentiated mesenchyme. Morphological perturbations of nephrogenesis, such as those seen in inherited renal diseases or induced in transgenic animals, require careful and often tedious documentation by multiple methodologies. We have applied a relatively quick and simple approach combining two-photon microscopy and advanced three-dimensional (3-D) imaging techniques to visualize and evaluate these complex events. As compared with laser confocal microscopy, two-photon microscopy offers superior optical sectioning deep into biological tissues, permitting analysis of large, heterogeneous, 3-D structures such as developing mouse kidney. Embryonic and newborn mouse kidneys were fluorescently labeled with lectins, phalloidin, or antibody. Three-dimensional image volumes were then collected. The resulting volume data sets were processed using a novel 3-D visualization technique. Reconstructed image volumes demonstrate the dichotomous branching of ureteric bud as it progresses from a simple, symmetrical structure into an elaborate, asymmetrical collecting system of multiple branches. Detailed morphology of in situ cysts was elucidated in a transgene-induced mouse model of polycystic kidney disease. We expect this integration of two-photon microscopy with advanced 3-D image analysis will provide a powerful tool for illuminating a variety of complex developmental processes in multiple dimensions.

Animals↗
PubMed2001

Carrier detection and rapid newborn diagnostic test for the common Y393N maple syrup urine disease allele by PCR-RFLP: culturally permissible testing in the Mennonite community.

The turnaround time for diagnosis of maple syrup urine disease (MSUD) by classic serum amino acid analyses often requires 3-4 days. This is due to the need for branched-chain amino acids (BCAA) to accumulate in the serum of the newborn before testing. The accumulation of BCAAs in infants with MSUD during this time increases the risk of the infant becoming clinically symptomatic. We have developed a noninvasive DNA-based mismatch PCR-RFLP assay for the Y393N BCKDHA allele (E1alpha gene of the branched chain alpha-keto acid dehydrogenase complex), the primary cause of MSUD in Old Order Mennonite communities. The homozygosity and high frequency of this mutation in the Mennonite community and its prevalence in compound heterozygote non-Mennonite MSUD patients is of significance. We describe carrier testing, present the results of nine newborns diagnostically evaluated for the Y393N BCKDHA allele, and demonstrate the efficacy of this PCR-RFLP assay for determining clinical status within 24 h after birth. Analyses within the first 24 h of life allow for immediate diagnosis and treatment of infants homozygous for the Y393N MSUD defect. This is a significant improvement over the time required by current serum amino acid analysis methods.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed2001

The role of type I collagen in aortic wall strength with a homotrimeric.

PURPOSE: Elastin and collagen (types I and III) are the primary load-bearing elements in aortic tissue. Deficiencies and derangements in elastin and type III collagen have been associated with the development of aneurysmal disease. However, the role of type I collagen is less well defined. The purpose of this study was to define the role of type I collagen in maintaining biomechanical integrity in the thoracic aorta, with a mouse model that produces homotrimeric type I collagen [alpha1(I)]3, rather than the normally present heterotrimeric [alpha1(I)]2 alpha2(I) type I collagen isotype. METHODS: Ascending and descending thoracic aortas from homozygous (oim/oim ), heterozygous (oim /+), and wildtype (+/+) mice were harvested. Circumferential and longitudinal load-extension curves were used as a means of determining maximum breaking strength (Fmax) and incremental elastic modulus (IEM). Histologic analyses and hydroxyproline assays were performed as a means of determining collagen organization and content. RESULTS: Circumferentially, the ascending and descending aortas of oim /oim mice demonstrated significantly reduced Fmax, with an Fmax of only 60% and 23%, respectively, of wildtype mice aortas. Oim/oim descending aortas demonstrated significantly greater compliance (decreased IEM), and the ascending aortas also exhibited a trend toward increased compliance. Reduced breaking strength was also demonstrated with longitudinal extension of the descending aorta. CONCLUSION: The presence of homotrimeric type I collagen isotype (absence of alpha2(I) collagen) significantly weakens the aorta. This study demonstrates the integral role of type I collagen in the biomechanical and functional properties of the aorta and may help to elucidate the role of collagen in the development of aneurysmal aortic disease or dissection.

Analysis of Variance↗
PubMed2001

Structure of a new crystal form of tetraubiquitin.

Polyubiquitin chains, in which the C-terminus and a lysine side chain of successive ubiquitin molecules are linked by an isopeptide bond, function to target substrate proteins for degradation by the 26S proteasome. Chains of at least four ubiquitin moieties appear to be required for efficient recognition by the 26S proteasome, although the conformations of the polyubiquitin chains recognized by the proteasome or by other enzymes involved in ubiquitin metabolism are currently unknown. A new crystal form of tetraubiquitin, which has two possible chain connectivities that are indistinguishable in the crystal, is reported. In one possible connectivity, the tetraubiquitin chain is extended and packs closely against the antiparallel neighbor chain in the crystal to conceal a hydrophobic surface implicated in 26S proteasome recognition. In the second possibility, the tetraubiqutitin forms a closed compact structure, in which that same hydrophobic surface is buried. Both of these conformations are quite unlike the structure of tetraubiquitin that was previously determined in a different crystal form [Cook et al. (1994), J. Mol. Biol. 236, 601--609]. The new structure suggests that polyubiquitin chains may possess a substantially greater degree of conformational flexibility than has previously been appreciated.

Biopolymers↗
PubMed2001

Measuring orthodontic treatment satisfaction: questionnaire development and preliminary validation.

OBJECTIVES: The aims of this study were to develop a reliable self-report measure of consumer satisfaction with orthodontic treatment, and to preliminarily assess its validity. METHOD: Transcripts of qualitative interviews with patients, their parents, and practicing orthodontists together with items from existing dental satisfaction questionnaires were used to develop a pool of 41 items assessing satisfaction with various aspects of orthodontic care. These items were paired with five-point Likert scales (1 = strongly disagree, 5 = strongly agree) and were administered to 299 parents of children who had completed orthodontic treatment at two university-based clinics. RESULTS: Factor analyses and reliability analyses identified three main subscales with high reliabilities: 13 items assessing satisfaction with treatment process (Cronbach's alpha = .92), seven items assessing satisfaction with psychosocial effects of treatment (Cronbach's alpha = .87), and five items assessing satisfaction with overall treatment outcome (Cronbach's alpha = .79). Relationships among these three subscales and pre- and posttreatment variables were examined in a subset of 86 parents/patients. Forward stepwise regression with backward overlook revealed no significant relationships between any satisfaction subscale and demographic variables. Posttreatment overjet was inversely related to parental satisfaction with orthodontic treatment process (R2 = .13; P < .001), and parent satisfaction with treatment outcome (R2 = .28; P < .0001). Improvement in esthetics as measured by improvement in IOTN Aesthetic Component scores was positively related to satisfaction with psychosocial outcomes (R2 = .28; P < .0001). CONCLUSIONS: The present instrument is reliable and can be used to assess three dimensions of parental satisfaction with their child's orthodontic treatment. Relationships between visible orthodontic outcome variables and parent satisfaction provide preliminary validity support for the instrument.

Adolescent↗
PubMed2001

Expression of cytolethal distending toxin and hemolysin is not required for pustule formation by Haemophilus ducreyi in human volunteers.

Haemophilus ducreyi makes cytolethal distending toxin (CDT) and hemolysin. In a previous human challenge trial, an isogenic hemolysin-deficient mutant caused pustules with a rate similar to that of its parent. To test whether CDT was required for pustule formation, six human subjects were inoculated with a CDT mutant and parent at multiple sites. The pustule formation rates were similar at both parent and mutant sites. A CDT and hemolysin double mutant was constructed and tested in five additional subjects. The pustule formation rates were similar for the parent and double mutant. These results indicate that neither the expression of CDT, nor that of hemolysin, nor both are required for pustule formation by H. ducreyi in humans.

Adult↗
PubMed2000

Oim mice exhibit altered femur and incisor mineral composition and decreased bone mineral density.

To investigate the role of the pro alpha 2(I) collagen chains of type I collagen in mineralization we used the oim (osteogenesis imperfecta model) mouse as our model system. The oim/oim mouse (homozygous for a null mutation in its COL1A2 gene of type I collagen) fails to synthesize functional pro alpha 2(I) collagen chains, synthesizing only homotrimers of pro alpha 1(I) collagen chains. To evaluate the role of pro alpha 2(I) collagen in type I collagen structure/function in mineralized tissues, we examined age-matched oim/oim, heterozygous (oim/+), and wild-type (+/+) mouse femurs and incisors for mineral composition (calcium, phosphorus, magnesium, fluoride, sodium, potassium, and chloride) by neutron activation analyses (NAA), and bone mineral content (BMC) and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) in a longitudinal study (7 weeks to 16 months of age). NAA demonstrated that oim/oim femurs had significant differences in magnesium, fluoride, and sodium content as compared with +/+ mouse femurs, and oim/oim teeth had significant differences in magnesium content as compared to +/+ teeth. The ratio of calcium to phosphate was also significantly reduced in the oim/oim mouse femurs (1.58 +/- 0.01) compared with +/+ femurs (1.63 +/- 0.01). DEXA demonstrated that oim/oim mice had significantly reduced BMC and BMD as compared to oim/+ and +/+ mice. Serum and urine calcium, magnesium, and phosphorus levels, and Ca(47) absorption across the gut were equivalent in oim/oim and +/+ mice, with no evidence of hypercalciuria. These studies suggest that the known decreased biomechanical properties of oim/oim bone reflect both altered mineral composition as well as the decreased BMD, which further suggests that the presence of alpha2(I) chains plays an important role in mineralization.

Absorptiometry, Photon↗
PubMed2000

Hyperoxic reperfusion exacerbates postischemic renal dysfunction.

BACKGROUND: Hyperoxic reperfusion from global ischemia worsens functional outcome because of oxygen radical-mediated injury. This study tested the hypothesis that hyperoxic reperfusion would exacerbate postischemic renal dysfunction. METHODS: Twenty-nine healthy, uninephrectomized, male mongrel rabbits (Oryctolagus cuniculus) in 3 groups were subjected to 30 minutes of complete normothermic renal ischemia followed by reperfusion under hyperoxic or normoxic conditions. The groups were: hyperoxically reperfused (n = 8), normoxically reperfused (n = 8), hyperoxic sham (no ischemia, n = 5), and allopurinol-pretreated (50 mg/kg, intravenously), hyperoxically reperfused animals (n = 8). Plasma concentrations of creatinine, urea nitrogen and electrolytes were measured at 0, 24, 48, and 72 hours after ischemia and served as functional outcome markers. Histopathologic analysis of kidneys for injury was performed by an expert who was blinded to the procedures. RESULTS: Plasma creatinine in hyperoxically reperfused rabbits was significantly elevated above normoxic (P =.02) and sham (P =.003) animals by 48 hours and remained elevated to 72 hours. Plasma urea nitrogen in hyperoxically reperfused rabbits was significantly elevated above the normoxic group (P = .01), the sham group (P = .02), and the allopurinol group (P = .04) by 72 hours. These coincided with a significantly elevated histopathologic injury score in hyperoxically reperfused rabbits compared with sham (P = .019), normoxic (P = .035), and allopurinol-pretreated hyperoxically reperfused animals (P = .037). CONCLUSIONS: Hyperoxic reperfusion exacerbates renal dysfunction after 30 minutes of complete normothermic ischemia. This dysfunction may be mediated by oxygen radical-related injury.

Allopurinol↗
PubMed1999

Diabetes mellitus and nontraumatic lower extremity amputation in black and white Americans: the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study, 1971-1992.

BACKGROUND: The comparative long-term risk of non-traumatic lower extremity amputation (LEA) in black and white Americans, 2 groups with strikingly different rates of diabetes mellitus, is not known. OBJECTIVE: To examine the 20-year incidence of LEA in relation to race and diabetes mellitus. METHODS: The 14 407 subjects in the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study were observed prospectively between 1971 and 1992. Prevalent diabetes mellitus was ascertained at the baseline examination, and incident diabetes mellitus, during follow-up. Lower extremity amputation was ascertained from hospital discharge records. Cox regression analysis was used to estimate associations between race, diabetes mellitus, and risk of first LEA. RESULTS: During the study period, 158 LEAs occurred among 108 subjects. While black subjects constituted 15.2% of the cohort, they represented 27.8% of the subjects with amputation (P = .002). The 20-year age-adjusted rate ratio of first LEAs for black subjects-white subjects was 2.14. Regression analyses confirmed the importance of diabetes mellitus as a key LEA risk factor. The association between prevalent diabetes mellitus and LEA risk was substantially higher (relative risk [RR], 7.19; 95% confidence interval [CI], 4.61-11.22) than that for incident diabetes mellitus (RR, 3.15 [CI, 1.84-5.37]), highlighting the importance of diabetes mellitus duration on LEA risk. While preliminary analyses adjusted for age and diabetes indicated a significant association between race and LEA risk (RR, 1.93 [95% CI, 1.26-2.96]), the effect of race diminished (RR, 1.49 [95% CI, 0.95-2.34]) following adjustment for education, hypertension, and smoking. CONCLUSIONS: Although black subjects experienced higher age- and diabetes mellitus-adjusted rates of amputation than their white counterparts, a combination of social and environmental factors may account for the apparent ethnic difference. More research into nonbiological factors associated with LEA may reduce the occurrence of these procedures in both black and white individuals.

Adult↗
PubMed1999

Insertional mutation of the collagen genes Col4a3 and Col4a4 in a mouse model of Alport syndrome.

Mice homozygous for the transgenic insertion in line OVE250 exhibit severe progressive glomerulonephritis. Ultrastructural changes in the glomerular basement membrane (GBM) at 2 weeks of age resemble those in Alport syndrome. The transgenic insertion site was mapped by FISH to mouse chromosome 1 close to Pax3. Genetic and molecular analyses identified a deletion of genomic DNA at the transgene insertion site. Exons 1 through 12 of the collagen IV gene Col4a4, exons 1 and 2 of the adjacent Col4a3 gene, and the intergenic promoter region are deleted. Transcripts of Col4a3 and Col4a4 are undetectable in mutant kidney, and both proteins are missing from the GBM. Persistent cellular proliferation in mutant kidneys suggests that interaction with the extracellular matrix may be important for cell maturation. Evolutionarily conserved sequence elements in the promoter regions of human and mouse Col4a3 and Col4a4 include a 19-bp element that was tandemly duplicated in the human lineage and a CTC box element common to several genes encoding extracellular matrix proteins. This new animal model of Alport syndrome, Col4Delta3-4, lacks both alpha3 and alpha4 chains of collagen IV and exhibits an earlier disease onset than mice lacking alpha3 only.

Animals↗
PubMed1999

Crystal structures of adenine phosphoribosyltransferase from Leishmania donovani.

The enzyme adenine phosphoribosyltransferase (APRT) functions to salvage adenine by converting it to adenosine-5-monophosphate (AMP). APRT deficiency in humans is a well characterized inborn error of metabolism, and APRT may contribute to the indispensable nutritional role of purine salvage in protozoan parasites, all of which lack de novo purine biosynthesis. We determined crystal structures for APRT from Leishmania donovani in complex with the substrate adenine, the product AMP, and sulfate and citrate ions that appear to mimic the binding of phosphate moieties. Overall, these structures are very similar to each other, although the adenine and AMP complexes show different patterns of hydrogen-bonding to the base, and the active site pocket opens slightly to accommodate the larger AMP ligand. Whereas AMP adopts a single conformation, adenine binds in two mutually exclusive orientations: one orientation providing adenine-specific hydrogen bonds and the other apparently positioning adenine for the enzymatic reaction. The core of APRT is similar to that of other phosphoribosyltransferases, although the adenine-binding domain is quite different. A C-terminal extension, unique to Leishmania APRTs, extends an extensive dimer interface by wrapping around the partner molecule. The active site involves residues from both subunits of the dimer, indicating that dimerization is essential for catalysis.

Adenine↗
PubMed1999

Smoking, physical activity, and active life expectancy.

The effect of smoking and physical activity on active and disabled life expectancy was estimated using data from the Established Populations for Epidemiologic Studies of the Elderly (EPESE). Population-based samples of persons aged > or = 65 years from the East Boston, Massachusetts, New Haven, Connecticut, and Iowa sites of the EPESE were assessed at baseline between 1981 and 1983 and followed for mortality and disability over six annual follow-ups. A total of 8,604 persons without disability at baseline were classified as "ever" or "never" smokers and doing "low," "moderate," or "high" level physical activity. Active and disabled life expectancies were estimated using a Markov chain model. Compared with smokers, men and women nonsmokers survived 1.6-3.9 and 1.6-3.6 years longer, respectively, depending on level of physical activity. When smokers were disabled and close to death, most nonsmokers were still nondisabled. Physical activity, from low to moderate to high, was significantly associated with more years of life expectancy in both smokers (9.5, 10.5, 12.9 years in men and 11.1, 12.6, 15.3 years in women at age 65) and nonsmokers (11.0, 14.4, 16.2 years in men and 12.7, 16.2, 18.4 years in women at age 65). Higher physical activity was associated with fewer years of disability prior to death. These findings provide strong and explicit evidence that refraining from smoking and doing regular physical activity predict a long and healthy life.

Aged↗
PubMed1999

Comparison of contrast sensitivity in different soft contact lenses and spectacles.

PURPOSE: To compare the visual performance of soft contact lenses and spectacles. METHODS: Twenty eyes of ten patients were examined. Each patient was fit with Acuvue, Cibasoft, and Biomedics contact lenses in random order. LogMar visual acuity and contrast sensitivity using the VectorVision CSV-1000 were measured. RESULTS: There was no significant difference in visual acuity between any contact lenses (P=.15). Contrast sensitivity at 12 cycles/degree was significantly lower for the Cibasoft lens compared to spectacles (P=.04). There was no significant difference between spectacles and contact lenses for remaining spatial frequencies (P=.07-.35). CONCLUSIONS: Visual acuity appears to be an insensitive method for evaluating soft contact lenses. The lathe-cut manufacturing process may be responsible for reduced visual function compared to cast-molded lenses. Further study in this area is needed.

Adult↗
PubMed1999

Assessment of health-related quality of life for patients with severe skeletal disharmony: a review of the issues.

Health-related quality of life (HRQOL) assessments made by patients provide a view of dentofacial disharmony and surgical outcome that can inform clinicians in important ways. In this paper, HRQOL as it pertains to patients with dentofacial disharmony and orthognathic surgery is discussed from three perspectives. First, arguments regarding the necessity of studying HRQOL in orthognathic patients are presented. Second, a variety of ways of defining HRQOL are reviewed, and implications for applications to orthognathic surgery are discussed. Finally, various measurement techniques are presented for assessing HRQOL in orthognathic patients. Use of dental HRQOL measures, as well as multi-item, multimeasure techniques, are discussed. For more reliable and comprehensive HRQOL measurement in patients with dentofacial disharmony, multi-item, multimeasurement techniques should be employed. While such techniques place greater demands on patients who are completing paper-and-pencil measures, the resultant low measurement error and comprehensive HRQOL assessment outweighs the risk of subject fatigue.

Humans↗
PubMed1998

Physical disability and social interaction: factors associated with low social contact and home confinement in disabled older women (The Women's Health and Aging Study).

OBJECTIVES: This study examines the association of disability and social interaction, measured as in-person contact with non-household members and home confinement, and identifies sociodemographic, socioeconomic, and health-related factors that modify this relationship. METHODS: Participants were 1,002 moderately to severely disabled community-dwelling women aged 65 and older from the Women's Health and Aging Study, identified by screening an age-stratified random sample of Medicare beneficiaries in Baltimore, Maryland. Logistic regression models were used to estimate the odds of low social interaction associated with disability and each independent modifier. RESULTS: In a typical week, 23% did not visit with anyone residing outside their households and 17% did not leave their homes. In addition to and independent of disability level, older age, not completing high school, having a driver in the home, hearing difficulties and incontinence were associated with low social contact; older age and African American race were related to home confinement. African American women living alone are especially vulnerable to home confinement. DISCUSSION: Physical disability is not necessarily socially disabling, as many of the most severely disabled in our study had at least daily social interaction. Improvements in social interaction appear possible through more effective management of certain health conditions and attention to potential sociocultural barriers.

Activities of Daily Living↗
PubMed1997

Chemosensory and somatosensory regeneration after lingual nerve repair in humans.

PURPOSE: The objective of these studies was to measure the impact of Class IV and V lingual nerve injuries on taste sensitivity and taste receptor density of the anterior tongue before and after microneurosurgical repair. MATERIALS AND METHODS: Citric acid detection threshold and suprathreshold magnitude response were measured on the anterior tongue in 12 adult volunteers with unilateral lingual nerve Class IV or V injuries. The right and left sides of the anterior tongue were tested at each session to assess the effect of nerve damage before and 1, 3, 6, and 12 months after repair. Whole-mouth threshold and suprathreshold scales of citric acid taste intensity were measured. The level of sensory impairment was scaled at each test session using a clinical neurosensory test algorithm. Finally, patients completed an 11-item instrument survey that queried the patient's perceived expectations of surgery on sensory, taste, and general health before surgery and the patient's perceived outcome of surgery at each postrepair session. The patient's perceived global satisfaction of surgery was also assessed. RESULTS: All 12 patients failed to detect and scale citric acid and had complete or severe sensory impairment on the injured side of the anterior tongue. One year after repair, 50% of the patients demonstrated a substantial increase in the number of fungiform papillae, pores, and ratio of pores/papilla at the same time as they demonstrated the ability to detect and scale citric acid. After repair, patients perceived the greatest improvements in the categories of eating, chewing, feeling, and taste, and the least in speech. CONCLUSION: Lingual nerve repair may result in significant changes in somatosensory and chemosensory function and taste bud anatomy on the anterior tongue over time.

Adult↗
PubMed1997

The effect of nitrous oxide on the measurement of single-breath transfer factor.

One hour after a bone marrow biopsy and inhalation of Entonox gas (50% nitrous oxide (N2O) and 50% oxygen), a patient had a markedly reduced transfer factor of the lung for carbon monoxide (TL,CO). Three hours after Entonox, the patient had a normal TL,CO. Since carbon monoxide (CO) and N2O have similar spectral wavelengths, it was proposed that residual N2O in the lungs was interfering with the infra-red analysers used to detect CO concentrations. Experiments were performed to verify the "interference" effect and its duration. Five healthy volunteers performed serial triplicate TL,CO measurements over 3 h on two randomized days (Control vs N2O). The first triplicate TL,CO on each day served as a baseline measurement. Following the baseline measurement on the N2O day, each subject inhaled Entonox for 10 min. To serve as a control for the infrared effect, the identical protocol was repeated using a gas chromatography method for TL,CO determination. The infra-red method showed a marked reduction (> 50%) in TL,CO 30 min after N2O inhalation. This reduction did not return to baseline levels for at least 2 h. In comparison, the gas chromatography method showed no significant reduction in TL,CO. In a group of healthy nonsmoking subjects, N2O markedly affected the measurement of the transfer factor of the lungs for carbon monoxide using infra-red analysers. The time course over which the measurement was reduced was at least 2 h for a 10 min inhalation period. The effect was entirely due to a measurement error associated with infra-red technology.

Adult↗