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Biomedical subjects

C L Phillips

Publications and source records attributed to C L Phillips.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

Cloning of the cDNA encoding human nonmuscle myosin heavy chain-B and analysis of human tissues with isoform-specific antibodies.

Previously, we reported the sequence of cDNA clones encoding amino acids 63 through 723 of the human nonmuscle myosin heavy chain-B isoform. In this paper, we present the derived sequence of the remaining 1303 amino acids along with 5' and 3' untranslated sequences. We made use of the differences between the derived nonmuscle myosin heavy chain-A and -B amino acid sequences to raise isoform-specific antibodies. Immunoblot analysis reveals a differential expression of both myosin heavy chain isoforms in a variety of human adult and foetal tissues and cells. When extracts of human adult aorta were subjected to gel electrophoresis, two distinct Coomassie Blue-stained bands and a fused band were seen migrating at approximately 200 kDa. These bands can be detected with four different specific antibodies recognizing the two different smooth muscle myosin heavy chain isoforms (204 kDa and 200 kDa) and the two different nonmuscle myosin heavy chain isoforms (A and B). Using immunohistochemistry, we confirmed the presence of the four different isoforms in adult and foetal aortas.

Amino Acid Sequence↗

Response of non-Hodgkin lymphoma to radiation therapy: early and long-term assessment with H-1 MR spectroscopic imaging.

PURPOSE: To determine whether proton magnetic resonance (MR) spectroscopic imaging is a sensitive technique for defining tumor extent and assessing response of cerebral lymphoma to therapy. MATERIALS AND METHODS: Four hydrogen-1 MR spectroscopic imaging studies were performed in a patient with non-Hodgkin lymphoma (NHL) before, during, and after radiation therapy and at follow-up at 33 months after diagnosis of the recurrence of disease. The patient had a single, large lesion in the brain and underwent hyperfractionated radiation therapy for 4 weeks. A series of MR images was also obtained. RESULTS: The pretreatment study showed a lesion with a distinct spectral pattern: marked elevation of choline and lipids and great reduction of creatine and N-acetylaspartate. During and after treatment, H-1 MR spectroscopic images depicted a progressive reduction of the abnormal choline and lipid signals. Thirty-three months after treatment, multiple-section H-1 MR spectroscopic images showed normal spectral patterns in all sections examined. CONCLUSION: H-1 MR spectroscopy may contribute to the neuroradiologic evaluation of NHL and, in particular, may be useful in monitoring therapeutic response.

Aspartic Acid↗

Heterodimerization of the yeast homeodomain transcriptional regulators alpha 2 and a1: secondary structure determination of the a1 homeodomain and changes produced by alpha 2 interactions.

The homeodomain proteins, a1 and alpha 2, act cooperatively to regulate cell-type specific genes in yeast. The basis of this cooperativity is an interaction between the two proteins, forming a heterodimer that binds DNA tightly and specifically. A fragment containing the homeodomain of a1, a1(66-126), has been studied by NMR spectroscopy to gain secondary structure information and to characterize the changes in a1 upon heterodimerization with alpha 2. Heteronuclear (1H-15N) NMR methods were used to assign backbone resonances of the 61 amino acid fragment. The a1(66-126) secondary structure was determined using NOE connectivities, 3JHN alpha coupling constants and hydrogen exchange kinetic data. NMR data identify three helical segments separated by a loop and a tight turn that are the characteristic structural elements of homeodomain proteins. The a1 fragment was titrated with alpha 2(128-210), the homeodomain-containing fragment of alpha 2, to study changes in a1(66-126) spectra produced by alpha 2 binding. The a1(66-126) protein was labeled with 15N and selectively observed using isotope-edited NMR experiments. NMR spectra of bound a1(66-126) indicate that residues in helix 1, helix 2, and the loop connecting them are directly involved in the binding of the alpha 2 fragment. Relatively minor effects on the resonances from residues in helix 3, the putative DNA-binding helix, were noted upon alpha 2 binding. We have thus located a region of the a1 homeodomain important for specific protein recognition.

Amino Acid Sequence↗

Heterodimerization of the yeast homeodomain transcriptional regulators alpha 2 and a1 induces an interfacial helix in alpha 2.

The homeodomain proteins a1 and alpha 2 act cooperatively to regulate cell type specific genes in yeast. The basis of the cooperativity is a weak interaction between the two proteins which forms heterodimers that bind DNA tightly and specifically. In this paper, we examine the mechanism of heterodimerization. We show that two relatively small fragments of a1 and alpha 2 are capable of heterodimerization and tight DNA binding. The alpha 2 fragment contains the homeodomain followed by the natural 22 C-terminal amino acids of the protein; these 22 amino acids are unstructured in the alpha 2 fragment. The a1 fragment contains only the homeodomain, indicating that the a1 homeodomain mediates both DNA binding and protein-protein interactions with alpha 2. We used isotope-edited NMR spectroscopy to study the interaction in solution of these two fragments. Samples in which only the alpha 2 fragment was uniformly labeled with 15N allowed us to visualize changes in the NMR spectra of the alpha 2 fragment produced by heterodimerization. We found that the a1 homeodomain perturbs the resonances of only the C-terminal tail of alpha 2; moreover, contact with a1 converts a portion of this tail (residues 193-203) from its unstructured state to an alpha-helix, as determined by J coupling and NOE measurements. Thus the heterodimerization of two homeodomain proteins involves the specific interaction between a tail of one protein and the homeodomain of the other. This interaction is accompanied by the acquisition of secondary structure in the tail.

Amino Acid Sequence↗

Effects of ascorbic acid on proliferation and collagen synthesis in relation to the donor age of human dermal fibroblasts.

Several events are associated with cellular aging: alterations in the extracellular matrix, loss of the cell's proliferative capacity, and decreased responsiveness to growth factors. In skin, a major component of the extracellular matrix is collagen; an important regulator of collagen synthesis is ascorbic acid, which may also have growth factor-like properties. To investigate the relationship of the extracellular matrix and proliferative capacity to aging, we examined the effects of ascorbic acid on cell proliferation and collagen expression in dermal fibroblasts from donors of two age classes, newborn (3-8 d old) and elderly (78-93 years old). In the absence of ascorbic acid (control) proliferative capacities were inversely related to age; newborn cell lines proliferated faster and reached greater densities than elderly cell lines. However, in the presence of ascorbic acid both newborn and elderly cells proliferated at a faster rate and reached higher densities than controls. To determine whether there are age-related differences in extracellular matrix production and ascorbic acid responsiveness we examined and found that collagen biosynthesis (collagenase-digestible protein) was inversely related to age, but the stimulation by ascorbic acid appeared age independent. The increase in collagen synthesis was reflected by coordinate increases in steady-state pro alpha 1(I) and pro alpha 1(III) collagen mRNAs, suggesting a pretranslational mechanism. Ascorbic acid appears capable of overcoming the reduced proliferative capacity of elderly dermal fibroblasts, as well as increasing collagen synthesis in elderly cells by similar degrees as in newborn cells even though basal levels of collagen synthesis are age dependent.

Aged↗

Differential localization of myosin-II isozymes in human cultured cells and blood cells.

We used purified polyclonal antibodies to human cytoplasmic myosin-IIA and myosin-IIB directly labeled with fluorescent dyes to localize these myosin-II isozymes in HeLa cells, melanoma cells and blood cells. Both antibodies react strongly with myosin-II isozymes in HeLa cells, melanoma cells and blood eosinophils, but only anti-myosin-IIA antibodies stain platelets, lymphocytes, neutrophils and monocytes in smears of human blood. Both antibodies stain small spots along the stress fibers of interphase HeLa cells and melanoma cells, but double staining revealed that the detailed distributions of myosin-IIA and myosin-IIB differ. A low concentration of diffuse myosin-IIB is present in the cortex, both in lamellar regions around the periphery of the cell and over the free surface. Myosin-IIB is also concentrated in spots along perinuclear stress fibers. Myosin-IIA is absent from the cortex but is concentrated in spots along stress fibers located near the basal surface of cultured cells. This population of peripheral stress fibers is highly enriched in myosin-IIA relative to myosin-IIB, but both are found together in centrally located stress fibers. In prophase and metaphase both isozymes are concentrated in the cortex in small spots less than 04.micron in size, similar to those in stress fibers. As the chromosomes begin the separate at anaphase, most of the myosin-II spots become concentrated in the outer 0.7 micron of the equatorial cortex in 100% of cells. This concentration of myosin-II isozymes in the cleavage furrow is maintained until the daughter cells separate. The superimposition of these small spots concentrated in the cleavage furrow produces the intense, uniform staining observed in conventional micrographs of whole cells.

Actins↗

Mutations in the COL1A2 gene of type I collagen that result in nonlethal forms of osteogenesis imperfecta.

Although virtually all mutations that result in osteogenesis imperfecta (OI) affect the genes that encode the chains of type I procollagen, the effects of mutations in the COL1A2 gene have received less attention than those in the COL1A1 gene. We have characterized mutations in 4 families that give rise to different OI phenotypes. In three families substitutions of glycine residues by cysteine in the triple helical domain (a single example at position 259 and 2 families in which substitution of glycine at 646 by cysteine) have been identified, and in the fourth a G for A transition at position +4 in intron 33 led to use of an alternative splice site and inclusion of 6 amino acids (val-gly-arg-ile-leu-phe) between residues 585 and 586 of the normal triple helix. The relation between position of substitution of glycine by cysteine in the COL1A2 gene does not follow the pattern developed in the COL1A1 gene. To determine how COL1A2 mutations produce OI phenotypes, we have produced a full-length mouse cDNA into which we plan to place mutations and examine their effects in stably transfected osteogenic cells and in transgenic animals.

Animals↗

Subtraction radiography to assess reproducibility of patient positioning in cephalometrics.

Subtraction radiography is a way to measure differences in landmark positions between cephalometric films without using tracings that introduce another source of error. This method was used to evaluate the reproducibility of head positioning in 54 pairs of cephalometric films taken within hours of each other, before and after splint removal in orthognathic surgery patients. There were no statistically significant changes in two cranial and four maxillary landmarks; the expected changes in mandibular landmark served to validate the method. The results suggest that patient positioning is not a major contributor to the error of cephalometric methods.

Cephalometry↗

Risk due to inactivity in physically capable older adults.

OBJECTIVES: This study examined the association between recreational physical activity among physically capable older adults and functional status, incidence of selected chronic conditions, and mortality over 3 and 6 years. METHODS: Data are from three sites of the Established Populations for Epidemiologic Studies of the Elderly. RESULTS: A high level of recreational physical activity reduced the likelihood of mortality over both 3 and 6 years. Moderate to high activity reduced the risk of physical impairments over 3 years; this effect diminishes after 6 years. A consistent relationship between activity and new myocardial infarction or stroke or the incidence of diabetes or angina was not found after 3 or 6 years. CONCLUSIONS: Findings suggest that physical activity offers benefits to physically capable older adults, primarily in reducing the risk of functional decline and mortality. Future work must use more objective and quantifiable measures of activity and assess changes in activity levels over time.

Activities of Daily Living↗

Ascorbic acid and transforming growth factor-beta 1 increase collagen biosynthesis via different mechanisms: coordinate regulation of pro alpha 1(I) and Pro alpha 1(III) collagens.

The specific mechanisms of collagen induction in human dermal fibroblasts by ascorbic acid and transforming growth factor-beta 1 (TGF-beta 1) and their effect in combination are uncertain. Collagen synthesis and steady-state levels of pro alpha 1(I) and pro alpha 1(III) collagen RNA were examined in human dermal fibroblasts treated with 100 microM ascorbic acid, 2.5 ng/ml TGF-beta 1, or both. Within 72 h ascorbic acid and TGF-beta 1 had increased collagen synthesis by 2.55 +/- 0.32- and 1.98 +/- 0.13-fold, respectively; in the presence of both, collagen synthesis increased 4.51 +/- 0.74-fold, appearing additive. Ascorbic acid acts specifically by increasing relative collagen synthesis whereas TGF-beta 1 increases overall protein synthesis. Steady-state levels of the pro alpha 1(I) collagen (5.8 and 4.8 kb) and pro alpha 1(III) collagen (5.4 and 4.8 kb) mRNAs were examined independently. Under each condition the steady-state levels of the longer transcripts for pro alpha 1(I) and pro alpha 1(III) collagens appeared coordinately and preferentially elevated. In the presence of both ascorbic acid and TGF-beta 1 the steady-state RNA levels did not increase in an additive manner, suggesting that the additive increase in collagen synthesis results from additional post-transcriptional mechanisms.

Ascorbic Acid↗

Sequence analysis of a full-length cDNA for the murine pro alpha 2(I) collagen chain: comparison of the derived primary structure with human pro alpha 2(I) collagen.

Comparison of the nucleotide sequence and primary structure of murine and human pro alpha 2(I) collagen indicates a high degree of homology: 87% at the nucleotide level and 87% at the amino acid level, with the greatest degree of variability in the amino- and carboxy-pro-peptide domains. The homology is greatest in the triple helical domain, repeating [Gly-X-Y]338, exhibiting 90% homology at the amino acid level, with only X and Y position residue substitutions. The X and Y residues show 86% homology between murine and human pro alpha 2(I) collagen triple helices, with no truly nonconservative substitutions.

Amino Acid Sequence↗

Serum albumin in older persons: relationship with age and health status.

We analyzed data from 4115 persons aged 71 years and older who had blood drawn at a home visit in three communities to examine the cross-sectional distribution of serum albumin and correlates of hypoalbuminemia. Mean albumin was lower among older persons, from 41.6 g/l in men aged 71-74 years to 38.5 g/l in men 90 years or older, and from 41.1 g/l to 38.9 g/l in women of the same ages, respectively. Hypoalbuminemia (albumin less than 35 g/l) was observed in 3.1% of subjects. Hypoalbuminemia and lower serum albumin were independently associated with anemia, recent diagnosis of cancer, two or more limitations in activities of daily living, residence in a nursing home, heavy cigarette smoking (greater than 1 pack/day), and older age. A 10-year age increment was associated with 0.8 g/l lower serum albumin and odds ratio of 1.56 (95% CI 1.14, 2.13) for hypoalbuminemia after adjusting for demographic factors and health status. Characteristics associated with serum albumin may confound the reported relationship between serum albumin and mortality.

Activities of Daily Living↗