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Biomedical subjects

C L Phillips

Publications and source records attributed to C L Phillips.

At least 55 records · Page 3Linked to original sources
PubMed1992

Inward rectification in Limulus ventral photoreceptors.

We examined inward rectification in Limulus ventral photoreceptors using the two-microelectrode voltage clamp. Hyperpolarization in the dark induced an inward current whose magnitude was distinctly dependent on extracellular K+ concentration, [K+0]. The [K+0] dependence resembled the characteristic [K+0] dependence of other inward rectifiers. The inward current was not dependent on extracellular Ca2+ or Na+, and it was unaffected by intracellular injection of Cl-. The hyperpolarization induced currents had two phases, an early nearly instantaneous phase and a slowly developing late phase. The currents were sensitive to extracellular barium and cesium. In voltage-pulse experiments, the magnitudes of the inwardly rectifying currents were variable from cell to cell, with some cells exhibiting negligible inward currents. Large hyperpolarizations (to membrane potentials more negative than about -140 mV) caused unstable inward current recordings, irreversible desensitization, and irreversible elevation of intracellular Ca2+ concentration. The inward rectifier provides negative feedback by tending to depolarize the cell (with inward current) in response to hyperpolarization. We suggest that the inward rectifier reduces the amount of hyperpolarization that would otherwise be generated by electrogenic processes. This feature would restrict the dynamic voltage range of the photoreceptors at very hyperpolarized potentials.

Animals↗
PubMed1992

Anemia and hemoglobin levels in older persons: relationship with age, gender, and health status.

OBJECTIVE: To determine the relationship of hemoglobin levels and anemia with age and health status in older adults. DESIGN: Survey. SETTING: Community. PARTICIPANTS AND METHODS: Hematologic tests were obtained from 3,946 adults aged greater than or equal to 71 years in three communities (East Boston, MA; Iowa and Washington counties, IA; and New Haven, CT). RESULTS: Hemoglobin level was inversely associated with age, although this was more pronounced in men than in women. The proportion anemic was equal for men and women aged 71-74 years (8.6%) and increased differentially with age, reaching 41% and 21% for men and women aged greater than or equal to 90 years, respectively. Hemoglobin and anemia were independently associated with age, race, body-mass index, smoking, cancer, hospitalization, renal insufficiency, and hypoalbuminemia. The adjusted relative odds of anemia for a 5-year increase in age was 1.5 (95% confidence interval [CI] 1.3-1.8) for men and 1.2 (95% CI 1.1-1.4) for women. CONCLUSIONS: Age is significantly associated with both hemoglobin levels and anemia, with a stronger effect in men compared with women, even after simultaneously adjusting for demographic characteristics and health status. The decline of hemoglobin and concomitant increased anemia with age is not necessarily a result of "normal aging" so the detection of anemia in an older person should prompt appropriate clinical attention.

Activities of Daily Living↗
PubMed1992

Fluoride intake from beverage consumption in a sample of North Carolina children.

Since the 1940's, the prevalence of dental fluorosis has increased in the US, concomitant with a reduction in dental decay. These changes have been attributed in part to the widespread use of systemic and topical fluorides. Various sources of increased systemic fluoride exposure have been investigated. However, little is known regarding fluoride intake from beverages in a sample of children of ages susceptible to dental fluorosis. The purpose of this study was to estimate the amount of fluoride ingested from beverages by a sample of North Carolina (NC) children of ages 2-10 years. Data on beverage consumption were collected by means of a diary format. A questionnaire was included so that demographic information and self-assessment on the accuracy of the diaries could be obtained. Beverages reported in the diaries were purchased, and their fluoride content was assayed. Daily total fluid intake ranged from 970 to 1240 mL, and daily beverage consumption ranged from 585 to 756 mL. The estimated mean daily fluoride intakes from beverages for children 2-3, 4-6, and 7-10 years of age were 0.36, 0.54, and 0.60 mg, respectively.

Age Factors↗
PubMed1991

The effects of different cysteine for glycine substitutions within alpha 2(I) chains. Evidence of distinct structural domains within the type I collagen triple helix.

Affected individuals from two apparently distinct, mild osteogenesis imperfecta families were heterozygous for a G to T transition in the COL1A2 gene that resulted in cysteine for glycine substitutions at position 646 in the alpha 2(I) chain of type I collagen. A child with a moderately severe form of osteogenesis imperfecta was heterozygous for a G to T transition that resulted in a substitution of cysteine for glycine at position 259 in the COL1A2 gene. Type I collagen molecules containing an alpha 2(I) chain with cysteine at position 259 denaturated at a lower temperature than molecules containing an alpha 2(I) chain with cysteine at position 646. In contrast to cysteine for glycine substitutions in the alpha 1(I) chain, the severity of the osteogenesis imperfecta phenotype is not directly proportional to the distance of the mutation from the amino-terminal end of the triple helix. These findings could be explained if the type I collagen triple helix contains discontinuous domains that differ in their contributions to maintaining helix stability.

Amino Acid Sequence↗
PubMed1991

Operational aspects of terminating randomization in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

The Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) is a randomized clinical trial sponsored by the National Eye Institute (NEI) designed to test whether cryotherapy applied to eyes of premature infants with a specified extent of stage 3+ ROP significantly decreases the incidence of an unfavorable outcome. An unfavorable outcome is defined as either retinal detachment or a retinal fold and was determined at 3 months posttreatment by the use of a masked photographic system. Enrollment into the trial was terminated on recommendation of the Data and Safety Monitoring Committee 9 months before the scheduled closing date for enrollment because of demonstrated treatment benefit. The purpose of this article is to discuss the operations involved in the orderly termination of enrollment and dissemination of results from this trial. These activities included preparation of trial participants and staff, release of trial information, continuing patient care, data collection and coding, and publication of trial results.

Blindness↗
PubMed1991

Relationship between vertical dentofacial morphology and respiration in adolescents.

The relationship between vertical dentofacial morphology and respiration has been debated and investigated from various approaches. The purpose of this study was to use contemporary respirometric techniques to compare the breathing behavior of normal and long-faced adolescents. Sixteen normal and 32 long-faced subjects 11 to 17 years of age were chosen clinically and verified by means of a discriminant function. Vertical and anteroposterior facial form was assessed from lateral cephalometric radiographs according to the following measurement criteria: six skeletal angular, eight skeletal linear, four dental linear, and three skeletal ratios. Breathing behavior was quantified according to tidal volume, minimum cross-sectional nasal area, and percent of nasal breathing as assessed by pneumotachography, measurement of differential pressures, and inductive plethysmography. The data indicated that the normal and long-faced groups were significantly different with respect to lower face form, and each group in the study was comparable to groups that had been chosen by previous investigators. Multiple regression analysis demonstrated that the normal and long-faced groups had similar tidal volumes and minimum nasal cross-sectional areas, but the long-faced subjects had significantly smaller components of nasal respiration. These results illustrate that groups without significant differences in airway impairment can have significantly different breathing modes that may be behaviorally based, rather than airway-dependent.

Adolescent↗
PubMed1991

Incidence and early course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group.

In the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (ROP), 4099 infants weighing less than 1251 g at birth underwent sequential ophthalmic examinations, beginning at age 4 to 6 weeks, to monitor the incidence and course of ROP. Overall, 65.8% of the infants developed ROP to some degree; 81.6% for infants of less than 1000 g birth weight. As expected, ROP incidence and severity were higher in lower birth weight and gestational age categories. Black infants appeared less susceptible to ROP, of all severity categories, than nonblack infants. The timing of retinal vascular events correlated more closely with postconceptional age than with postnatal age, implicating the level of maturity more than postnatal environmental influences in governing the timing of these vascular events. These results include the current incidence of various severity stages of ROP found in the United States and provide new insight into the development of ROP.

Cryosurgery↗
PubMed1991

Effects of external lithium on the physiology of Limulus ventral photoreceptors.

We have examined some of the physiological effects associated with the replacement of extracellular Na+ with Li+ in nominally Ca(2+)-free saline in the ventral photoreceptors of the horseshoe crab Limulus polyphemus. We observed that replacement of Na+ saline with Li+ saline induced larger voltage-activated inward currents with similar voltage dependence. These currents were absent in Tris+ saline. Anode-break excitation was maintained in Li+ saline but blocked in Tris+ saline. Regenerative events associated with quantum bumps in dark-adapted cells illuminated with dim lights were maintained in Li+ saline. Regenerative events associated with responses to moderately bright illumination were also maintained in Li+ saline. The post-illumination hyperpolarization associated with the Na+/K(+)-exchange pump (Brown & Lisman, 1972) was present after brief exposure to Li+ saline but disappeared after longer exposure. Following return to Na+ saline, the post-illumination hyperpolarization reappeared. We conclude that (1) Li+ permeates the voltage-dependent Na+ channel, GNa(V), in the photoreceptor plasma membrane; (2) Li+ supports voltage-activated physiological events normally mediated by Na+; and (3) Li+ substitution briefly supports and later inhibits the electrogenic effects of the Na+/K(+)-exchange pump. The effects of external Li+ on cellular physiology have implications for the interpretation of other studies employing Li+ extracellularly.

Animals↗
PubMed1991

The gene encoding ovine follicle-stimulating hormone beta: isolation, characterization, and comparison to a related ovine genomic sequence.

Follicle-stimulating hormone (FSH), the primary stimulus for egg and sperm maturation in mammals, is an alpha/beta heterodimer. Each subunit is encoded by a single-copy gene in the human, bovine, and rat genomes. Transcription of both subunits is inhibited by estradiol and progesterone in ovine pituitary cultures. We report the sequence of one ovine FSH-beta gene (-1,527 to +3,664) that is expressed in vivo and the identification of a novel, second ovine FSH-beta-like sequence. Digestion of ovine genomic DNA with Bgl II yielded two fragments of 10 kb and 15 kb that hybridized to a bovine FSH-beta cDNA. The 10-kb fragment contained 6 kb of 5'-flanking region and all but about 200 bp of the 3' terminus of the ovine FSH-beta gene. This FSH-beta gene encodes a protein that differs from the published ovine protein sequence only at the carboxy terminus (Arg-109Glu-110[STOP codon] instead of Glu-109Arg-110[Glx-111]) and at positions 49 (Ala instead of Thr) and 88 (Arg instead of Ser). This gene is organized similarly to the human, bovine, porcine, and rat FSH-beta genes, and its coding sequence is nearly identical (99.5%) to a reported ovine FSH-beta cDNA. Expression of the FSH-beta gene on the 10-kb fragment in vivo was determined by analysis of wether mRNA using the polymerase chain reaction. A 95-bp sequence of the 15-kb fragment was 87% homologous to the corresponding coding region of the 10-kb fragment. This comparison suggested that the 15-kb fragment contains either an FSH-beta-like sequence or a pseudogene. Several potential steroid response elements were found by sequence analysis of the 5'-flanking region of the FSH-beta gene on the 10-kb fragment. A mechanism by which these elements may act is suggested.

Amino Acid Sequence↗
PubMed1991

Secondary structure of the homeo domain of yeast alpha 2 repressor determined by NMR spectroscopy.

The yeast alpha 2 protein is a regulator of cell type in Saccharomyces cerevisiae. It represses transcription of a set of target genes by binding to an operator located upstream of each of these genes. The alpha 2 protein shares weak sequence similarity with members of the homeo domain family; the homeo domain is a 60-amino-acid segment found in many eukaryotic transcriptional regulators. In this paper we address the question of whether alpha 2 is structurally related to prototypical members of the homeo domain family. We used solution 1H and 15N nuclear magnetic resonance [NMR] spectroscopy to determine the secondary structure of an 83-amino-acid residue fragment of alpha 2 that contains the homeo domain homology. We have obtained resonance assignments for the backbone protons and nitrogens of the entire 60-residue region of the putative homeo domain and for most of the remainder of the alpha 2 fragment. The secondary structure was determined by using NOE connectivities between backbone protons, 3JHN-H alpha coupling constants, and dynamical information from the hydrogen exchange kinetics of the backbone amides. Three helical segments exist in the alpha 2 fragment consisting of residues 11-23, 32-42, and 46-60 (corresponding to residues 138-150, 159-169, and 173-187 of the intact protein). The positions of these three helices correspond extremely well to those of the Drosophila Antennapedia (Antp) and engrailed (en) homeo domains, whose three-dimensional structures have recently been determined by NMR spectroscopy and X-ray crystallography, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Construction of a full-length murine pro alpha 2(I) collagen cDNA by the polymerase chain reaction.

Construction of large collagen cDNA has been hindered by the relatively large size and high G-C content of processed mRNA. We describe here the development of a rapid and efficient method for obtaining large full-length collagen cDNA. A full-length (4.3 kb) murine pro alpha 2(I) collagen cDNA was constructed by synthesis of a first-strand cDNA library with use of poly-A RNA (MC3T3-E1) and the oligo-dT17-adapter primer described by Frohman et al (Proc Natl Acad Sci USA 85:8998, 1988). Pro alpha 2(I) collagen cDNA were specifically amplified by the polymerase chain reaction (PCR) with a pro alpha 2(I) specific primer as the 5' primer (20mer; corresponding to nucleotide positions 42-61 in the first exon of the murine pro alpha 2(I) collagen gene, COL1A2), and with the adapter sequence 5' to the dT17 as the 3' primer. The PCR conditions were optimized to allow amplification of the expected 4.0-5.0-kb product; a major 4.3-kb product was visualized by ethidium bromide, identified by in situ gel hybridization, and cloned. DNA sequencing determined that it contained the correct 5' sequence and the 3' end had a 68 basepair (bp) 3' untranslated region. The entire sequence that codes the amino-terminal propeptide domain has been determined and compared to the human sequence. The homology between human and mouse is less in the amino terminal propeptide than in the triple helical domain; exon 5 of murine COL1A2 codes for an additional six amino acids not found in human COL1A2.

Amino Acid Sequence↗
PubMed1990

Interstitial adenosine in guinea pig hearts: an index obtained by epicardial disks.

Epicardial porous disks were used to estimate left ventricular interstitial fluid adenosine in the isolated guinea pig heart perfused at constant flow. To validate this technique, adenosine was infused with 0.5 microM dipyridamole and 5 microM erythro-4-(2-hydroxy-3-nonyl)adenine hydrochloride (EHNA) to inhibit adenosine uptake and deamination, respectively. Under these conditions, with 6 or 12 microM adenosine in the arterial infusate, the venous and steady-state left ventricular disk adenosine values equaled those of the perfusion fluid, reflecting the expected equilibration between vascular and left ventricular interstitial fluid (disk) compartments. The concentration of endogenous adenosine in the interstitial fluid as estimated by the epicardial disks under control conditions was 0.28 +/- 0.03 microM with a concomitant coronary sinus concentration of 0.004 +/- 0.001 microM. We conclude that a marked adenosine gradient exists between the interstitial fluid and the vascular space and that disk adenosine measurements provide a useful index of left ventricular interstitial fluid adenosine.

Adenosine↗
PubMed1990

A substitution at a non-glycine position in the triple-helical domain of pro alpha 2(I) collagen chains present in an individual with a variant of the Marfan syndrome.

A substitution for a highly conserved non-glycine residue in the triple-helical domain of the pro alpha 2(I) collagen molecule was found in an individual with a variant of the Marfan syndrome. A single base change resulted in substitution of arginine618 by glutamine at the Y position of a Gly-X-Y repeat, and is responsible for the decreased migration in SDS-polyacrylamide gels of some pro alpha 2(I) chains of type I collagen synthesized by dermal fibroblasts from this individual. Family studies suggest that this substitution was inherited from the individual's father who also produces abnormally migrating pro alpha 2(I) collagen chains and shares some of the abnormal skeletal features. This single base change creates a new Bsu36 I (Sau I, Mst II) restriction site detectable in genomic DNA by Southern blot analysis when probed with a COL1A2 fragment. The analysis of 52 control individuals (103 chromosomes) was negative for the new Bsu36 I site, suggesting that the substitution is not a common polymorphism.

Adult↗
PubMed1989

Tooth crazing associated with threaded pins: a three-dimensional model.

A model for observing the three-dimensional pattern of cracking associated with placement of self-threading retentive pins was developed. Four sizes of self-threading pins were placed in extracted posterior tooth samples. The pins were subsequently removed and the samples coated with butyl acetate lacquer except for the pin channel orifice. Samples were immersed in dye solution followed by a demineralization and dehydration process. Samples were placed in methyl salicylate until cleared. Cleared samples were examined for dye penetration into the pin channel and communication with the pulp chamber. Comparisons were made of the patterns created by the four sizes of retentive pins. Results showed that more extensive cracks occurred with the larger size pins and that crack communication with the pulp chamber occurred more frequently with the larger pins.

Acetates↗
PubMed1988

The effect of L-glutamic acid on airway function and reactivity in the rabbit.

The ingestion of monosodium glutamate in sensitive individuals has been reported to cause severe asthma. We therefore studied the effects of L-glu on airway function and histamine (H) responsiveness in the rabbit. Histamine dose response curves (HDR's) were performed by measuring total lung resistance (RL) after inhalation of saline and increasing concentrations of H (1-30 mg/ml). The concentration of H producing a 20% increase in RL (PC20H) was obtained by interpolation. To assess the effects of L-glu, 8 rabbits were infused with L-glu (0.2 g/kg/hr) or saline in random order (14 days apart) for 4 hours followed by an HDRC. To look at possible late effects, a repeat HDRC was also performed in 6 rabbits 12 hours after completion of the L-glu infusion. In order to see whether rabbits rendered hyperresponsive responded to L-glu, the above protocol was performed in 7 rabbits following the inhalation of 3 micrograms of the activated complement fragment C5a des Arg. The L-glu infusions increased the plasma levels approx. ten-fold (mean +/- SEM 0.119 +/- 0.012 base-line, 1.272 +/- 0.061 mmol/l post infusion). L-glu did not increase the PC20H or baseline RL in either the normal rabbits at 4 or 12 hours or in the C5a des Arg treated rabbits at 4 hours. It is concluded that L-glu does not cause bronchoconstriction or an increase in airway responsiveness to H in the rabbit.

Administration, Inhalation↗
PubMed1988

17 Beta-estradiol and progesterone inhibit transcription of the genes encoding the subunits of ovine follicle-stimulating hormone.

FSH, the primary trophic hormone for gamete development in mammals, is composed of two protein subunits, alpha and beta. It is known that 17 beta-estradiol (E2) and progesterone (P4) can decrease the secretion and synthesis of FSH in ovine pituitary cultures. Data presented here indicate that E2 and P4 decrease the steady state levels of FSH beta mRNA concomitantly with FSH secretion in ovine pituitary cultures. By 24 h, E2 decreased the steady state levels of FSH beta mRNA and FSH secretion by 68% +/- 5%. P4 also decreased both concomitantly, but by 58% +/- 7% after 24 h. E2 and P4 also decrease steady state levels of alpha mRNA, but at a lower rate. Finally, it is shown that E2 and P4 decrease transcription of the FSH beta by greater than 85% in 2 h; alpha mRNA transcription is decreased by 70% in 12 h. These effects are not altered even when cycloheximide is present to block protein synthesis by 95%. These data further define the mechanisms whereby E2 and P4 inhibit ovine FSH secretion/synthesis directly at the pituitary level. They also provide the first example of negative transcriptional regulation by P4 and the second of two examples now established for E2.

Animals↗
PubMed1986

Circular differential scattering and circular differential absorption of DNA-protein condensates and of dyes bound to DNA-protein condensates.

DNA-protein condensates that give positive and negative psi-type circular dichroism (CD) spectra (psi condensates) bind intercalative and nonintercalative dyes. CD depends both on circular differential scattering and on circular differential absorption; scattering-corrected CD measurements are approximations to circular differential absorption. The circular differential scattering and scattering-corrected CD patterns observed in the DNA absorption band of psi condensates are mimicked in the induced CD band of intercalators bound to psi condensates. The induced scattering-corrected CD and circular differential scattering patterns of the groove-binding dye Hoechst 33342 bound to psi condensates are the inverse of the patterns seen with intercalative dyes, whereas the groove-binding dye manganese(III) meso-tetrakis(4-N-methylpyridyl)porphine [MnIIITMpyP-4] shows no significant induced CD patterns. The large circular differential scattering and scattering-corrected CD bands are interpreted as resulting from long-range chiral packing, rather than near-neighbor short-range interactions. Dyes intercalated into the DNA of the psi condensates have the same type of long-range chiral packing as the DNA bases. Therefore, the psi-type CD spectra seen in the UV spectra originating from the long-range packing of the DNA bases are also observed in the visible spectra when dyes are intercalated in the DNA of the psi condensates. Our interpretation comes from the observation that the induced circular differential scattering and circular differential absorption of the dye bound to the psi condensates depend only upon the sign of the circular differential absorption and the pattern of the circular differential scattering of the psi condensates without bound dye.(ABSTRACT TRUNCATED AT 250 WORDS)

Circular Dichroism↗