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C Phillips

Publications and source records attributed to C Phillips.

At least 127 records · Page 7Linked to original sources
PubMed1996

A gene map of the human genome.

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.

Amino Acid Sequence↗
PubMed1996

Dissociation of glomerular hypertrophy, cell proliferation, and glomerulosclerosis in mouse strains heterozygous for a mutation (Os) which induces a 50% reduction in nephron number.

We reported that the Os mutation in ROP mice induced a 50% reduction in nephron number, glomerular hypertrophy, and severe glomerulosclerosis. We examined two mouse strains with the Os mutation, ROP Os/+ and C57 Os/+ mice, to determine whether the genetic background influenced the development of glomerulosclerosis. Nephron number was decreased by 50% in both ROP Os/+ and C57 Os/+ mice, and a glomerular volume and labeling index were two- to threefold increased in both. Whereas glomerulosclerosis was severe in ROP Os/+ mice, it was absent or minimal in C57 Os/+ mice. ROP Os/+ glomeruli had two- to threefold more type IV collagen, laminin, and tenascin than C57 Os/+ by immunofluorescence microscopy. Glomerular alpha 1IV collagen and tenascin mRNA levels were increased (2.8- and 1.7-fold) in ROP Os/+ and in C57 Os/+ (1.7- and 1.4-fold) mice. Both ROP Os/+ and C57 Os/+ mice had a slight increase (1.5- and 1.7-fold) in 72-kD collagenase mRNA levels. Whereas laminin B1 mRNA levels were twofold higher in ROP +/+ than in C57 +/+ mice, there was no further change in the presence of the Os mutation. Thus, the response to the Os mutation depended on the mouse strain, since severe glomerulosclerosis occurred only in ROP Os/+ mice, even though cell proliferation and glomerular hypertrophy also were present in C57 Os/+ mice.

Animals↗
PubMed1996

Inducible nuclear factors binding the IgM heavy chain pre-mRNA secretory poly(A) site.

Two alternative forms of IgM heavy-chain mRNA are produced from a common precursor mRNA as a result of competition between cleavage/poly(A) addition at the upstream (secretory) poly(A) site and cleavage/poly(A) addition at the downstream (membrane) poly(A) site coupled with splicing. The efficiency of cleavage at the secretory poly(A) site is thought to play a crucial role in this alternative processing. We therefore examined RNA binding factors recognizing the secretory poly(A) site, in the absence of the splicing option, to look for transacting factors that may play a role in cleavage/polyadenylation efficiency at this site. Purified primary B cells produce the secretory form of mu mRNA when stimulated with lipopolysaccharide (LPS) and the membrane form of mu mRNA when their antigen receptors are ligated by anti-mu antibodies. We compared RNA binding factors in nuclear extracts from cells produced by these different stimulatory conditions and show that induction of the secretory form of mu mRNA by LPS correlates with the induction of a 28-32-kDa secretory poly(A) site-specific polypeptide which is also present in the plasmacytoma cell line J558L. Visualization of the 28-32-kDa polypeptide in UV cross-linking assays depends on a GU-rich element downstream of the secretory poly(A) site. We show that this GU-rich region enhances polyadenylation efficiency in vivo by transfection of luciferase reporter constructs into the plasmacytoma J558L. We also examined nuclear extracts from B cells doubly stimulated with LPS and anti-mu antibodies in which expression of the secretory form of mu mRNA is selectively inhibited. This inhibition may be due to a down-regulation of polyadenylation at the secretory poly(A) site or an up-regulation of the competitive splicing process. This form of stimulation does not lead to the disappearance of the 28-32-kDa polypeptide, but to an enhanced binding of a 50-55-kDa factor which binds both the secretory and membrane poly(A) site. We report the first detection of changes in RNA binding factors taking place at the secretory poly(A) site which correlate with the expression of different forms of mu mRNA produced by primary B cells under different stimulation conditions.

Animals↗
PubMed1996

Clinical/biological outcomes of treatment for pericoronitis.

PURPOSE: This prospective clinical study was designed to determine the clinical and biologic outcomes of treatment for minor signs and symptoms of pericoronitis. PATIENTS AND METHODS: Patients (n = 20) with all third molars, presenting consecutively to an academic clinical center for treatment of minor signs and symptoms of pericoronitis, were enrolled in the study. At the initial visit, gingival crevicular fluid (GCF) samples to assess levels of the cytokines interleukin- 1b (IL-1b) IL-1b and prostaglandin E2 (PGE2) as a measure of the host inflammatory response, and plaque samples to identify microorganisms, were collected from the distal of all second molars and the mesial of first molars. Standardized vertical bite wing radiographs were taken to assess alveolar bone height on the distal of the second molars and the inclination and the degree of eruption of the third molar. Full-mouth periodontal probing was conducted to determine probing depths and relative clinical attachment levels (CAL). Pain levels were assessed with Gracely verbal descriptor scales for sensory intensity and unpleasantness and 10-cm visual analog scales. Symptomatic third molar sites were treated with local debridement and irrigation after baseline data collection. One week after entry, data were collected again. Subsequently, the patients were scheduled for removal of all third molars. Data collection was repeated 3 months postsurgery. As controls, data were collected from 12 subjects who had asymptomatic third molars removed previously. RESULTS: At entry, symptomatic mandibular third molars (n = 21) were mostly vertical (n = 18) and at or above the occlusal plane (n = 19). No maxillary teeth had symptoms. Microbial counts were elevated for specific anaerobic microorganisms. GCF IL-1b levels were elevated at the distal of second molars adjacent to symptomatic third molars, as compared with asymptomatic third molars and second molars in control patients. Alveolar bone levels and CAL on the distal of second molars were normal. At 1 week, patients' pain symptoms and IL-1b levels were reduced, but microbial counts remained high. Three months after surgery, patients had no pain symptoms, and alveolar bone levels and CAL were similar to entry levels. IL-1b levels were elevated at both the distal of second molars and the mesial of first molars for all patients; microbial counts decreased, although not to levels of control patients. No increase in microbial counts for Porphyromonas gingivalis or Bacteroides forsythus, or GCF PGE2 levels, risk factors for progressive periodontal disease, was detected in samples taken from the study patients. CONCLUSION: Pericoronitis expressed by minor signs/symptoms in these patients was associated with considerable discomfort. Symptomatic mandibular third molars were vertical and at or near the occlusal plane. Additionally, this condition was characterized by microbial flora and GCF inflammatory mediator levels that are more consistent with gingivitis than periodontitis. Removal of third molars eliminated symptoms, but the microbial burden and an affected patient's inflammatory response, as measured by IL-1b levels, remained elevated as compared with controls. Further study is needed to determine which of these factors can be used to identify patients at risk for pericoronitis before symptoms arise.

Adolescent↗
PubMed1996

Mechanical analysis of the palmar aponeurosis pulley in human cadavers.

The anatomy of the palmar aponeurosis pulley has been well described, but its biomechanical function is not as well characterized. This study describes the functional importance of the palmar aponeurosis pulley by using efficiency parameters. We obtained data by generating load, excursion, and work efficiencies in the intact pulley system and compared these to the efficiencies obtained after sectioning the palmar aponeurosis pulley alone and in combination with the proximal annular pulleys. The variability associated with comparisons between different fingers and hands was therefore diminished. Sectioning the palmar aponeurosis pulley alone did not significantly change any of the efficiency parameters. When the palmar aponeurosis pulley was sectioned in combination with either or both of the proximal annular pulleys (A1, A2) there was a significant decrease in excursion efficiency. Only after all three proximal pulleys were sectioned did the load efficiency increase and the work efficiency decrease significantly. These findings prove that the palmar aponeurosis pulley in combination with the proximal annular pulleys acts to decrease the tendency to bowstringing around the metacarpophalangeal joint. The increased load efficiency is probably the result of a decrease in friction and counteractive forces generated by the integrated fibers of the intact palmar aponeurosis pulley. Change in work is due not only to an increase in excursion, but also to the increased resistance that results from the acute angulation that the tendon must endure as it follows behind the remaining pulleys during flexion. Intergroup comparisons show a significant contribution by the palmar aponeurosis pulley. This study demonstrates a significant biomechanical role for the palmar aponeurosis pulleys and suggests that it be considered similar to the annular and cruciate flexor tendon pulleys in importance.

Biomechanical Phenomena↗
PubMed1996

Task-induced asymmetry of the auditory evoked M100 neuromagnetic field elicited by speech sounds.

The auditory evoked neuromagnetic fields elicited by synthesized speech sounds (consonant-vowel syllables) were recorded in six subjects over the left and right temporal cortices using a 37-channel SQUID-based magnetometer. The latencies and amplitudes of the peaks of the M100 evoked responses were bilaterally symmetric for passively presented stimuli. In contrast, when subjects were asked to discriminate among the same syllabic stimuli, the amplitude of the M100 increased in the left and decreased in the right temporal cortices. Single equivalent current dipole modeling of the activity elicited by all stimulus-types localized to a well-circumscribed area in supratemporal auditory cortex. The results suggest that attentional modulation affects the two supratemporal cortices in a differential manner. Task-conditioned attention to speech sounds is reflected in lateralized supratemporal cortical responses possibly concordant with hemispheric language dominance.

Acoustic Stimulation↗
PubMed1996

Inhibition of diabetic nephropathy by a GH antagonist: a molecular analysis.

Streptozotocin-treated C57B1/SJL mice developed glomerular hypertrophy and light microscopic lesions mimicking human diabetic glomerulosclerosis. In contrast, there were no glomerular hypertrophy and lesions in diabetic mice transgenic (TG) for a mutated growth hormone (bGH-G119K) that competes with native endogenous GH and results in dwarfism. We examined the molecular events underlying these findings. The non-transgenic (non-TG) diabetic mouse glomeruli had an increase in mRNA coding for alpha 1IV collagen, laminin B1, TGF-beta 1, 72 kDa collagenase, and TIMP-3. In contrast, glomerular type IV collagen and laminin B1 mRNA levels were normal in diabetic TG dwarf mice. However, the 72 kDa gelatinase, TIMP-3, and TGF-beta 1 mRNAs were elevated in the diabetic dwarfs. Type IV collagen and laminin accumulated in the glomeruli of diabetic non-TG, but not of diabetic dwarf mice, by immunofluorescence microscopy, confirming the mRNA data. GH binding protein mRNA levels were comparable in glomeruli from dwarf and non-TG mice, both diabetic and non-diabetic. We did not detect GH receptor mRNA in glomeruli. These data suggest that diabetic glomerulosclerosis is associated with an increase in type IV collagen and laminin synthesis, and that these changes do not occur in mice transgenic for bGH119K, a functional antagonist of GH. The increase of 72 kDa gelatinase, TIMP-3 and TGF-beta 1 mRNAs, independent of GH, suggested that these changes induced by hyperglycemia were not sufficient for the induction of glomerulosclerosis.

Animals↗
PubMed1996

Middle fossa cyst presenting as a delayed complication of temporal lobectomy: case report.

Symptomatic middle fossa cysts have not previously been described as complications of temporal lobectomy that has been performed to control complex partial seizures. A patient is described who developed a middle fossa cyst causing mass effect, intracranial hypertension, and neurological deterioration > 2 years after temporal lobectomy for complex partial seizures. An enlarging cyst with cerebrospinal fluid imaging characteristics was detected on neuroimages 1 year before neurological deterioration. The patient was treated by the insertion of a cystoperitoneal shunt for cerebrospinal fluid diversion. The potential causes of an acquired arachnoid cyst and hydrocephalus are discussed.

Adult↗
PubMed1996

Quality in provision of forensic psychiatric services: room for improvement.

Highlights some of the tensions which impede the development of an effective and efficient system of service delivery in forensic psychiatry. Reports on an investigation exploring the quality of care in a relatively small unit providing forensic psychiatric care in a secure setting and the constraints which impede the development of such services. Discusses the findings from the investigation which point to the need for the organizational structure surrounding forensic psychiatric care to be altered so that there are no perverse incentives for purchasers of services and to enable the contracting process, considering both cost and quality issues, to take place on a level playing field.

Australia↗
PubMed1996

Orthognathic surgery: a hierarchy of stability.

The stability and predictability of orthognathic surgical procedures varies by the direction of surgical movement, the type of fixation, and the surgical technique employed, largely in that order of importance. The most stable orthognathic procedure is superior repositioning of the maxilla, closely followed by mandibular advancement in patients in whom anterior facial height is maintained or increased. (If facial height is decreased by upward rotation of the chin, stability is compromised). The combination of moving the maxilla upward and the mandible forward is significantly more stable when rigid internal fixation is used in the mandible. Forward movement of the maxilla is reasonably stable, with or without rigid internal fixation, but mandibular setback often is not stable, and downward movement of the maxilla that creates downward rotation of the mandible is unstable. For mandibular setback, the inclination of the ramus at surgery appears to be an important influence on stability. It has been suggested that both interpositional synthetic hydroxyapatite grafting and simultaneous ramus osteotomy improve the stability of downward movement of the maxilla, but this has not been well documented. In two-jaw Class III surgery, the stability of each jaw appears to be quite similar to that of isolated maxillary advancement or mandibular setback. The least stable orthognathic procedure is transverse expansion of the maxilla. Although surgically assisted rapid palatal expansion has been suggested as a more stable alternative to segmental Le Fort I osteotomy, the patterns of movement resulting from the two procedures are different, and differences in stability have not been established.

Humans↗
PubMed1995

The crystal structure of the catalytic domain of human urokinase-type plasminogen activator.

BACKGROUND: Urokinase-type plasminogen activator (u-PA) promotes fibrinolysis by catalyzing the conversion of plasminogen to the active protease plasmin via the cleavage of a peptide bond. When localized to the external cell surface it contributes to tissue remodelling and cellular migration; inhibition of its activity impedes the spread of cancer. u-PA has three domains: an N-terminal receptor-binding growth factor domain, a central kringle domain and a C-terminal catalytic protease domain. The biological roles of the fibrinolytic enzymes render them therapeutic targets, however, until now no structure of the protease domain has been available. Solution of the structure of the u-PA serine protease was undertaken to provide such data. RESULTS: The crystal structure of the catalytic domain of recombinant, non-glycosylated human u-PA, complexed with the inhibitor Glu-Gly-Arg chloromethyl ketone (EGRcmk), has been determined at a nominal resolution of 2.5 A and refined to a crystallographic R-factor of 22.4% on all data (20.4% on data > 3 sigma). The enzyme has the expected topology of a trypsin-like serine protease. CONCLUSIONS: The enzyme has an S1 specificity pocket similar to that of trypsin, a restricted, less accessible, hydrophobic S2 pocket and a solvent-accessible S3 pocket which is capable of accommodating a wide range of residues. The EGRcmk inhibitor binds covalently at the active site to form a tetrahedral hemiketal structure. Although the overall structure is similar to that of homologous serine proteases, at six positions insertions of extra residues in loop regions create unique surface areas. One of these loop regions is highly mobile despite being anchored by the disulphide bridge which is characteristic of a small subset of serine proteases namely tissuetype plasminogen activator, Factor XII and Complement Factor I.

Amino Acid Sequence↗
PubMed1995

Structure of 6-phosphogluconate dehydrogenase refined at 2 A resolution.

The X-ray unliganded structure of 6-phosphogluconate dehydrogenase (E.C. 1.1.1.44) (6-PGDH) from sheep liver has been determined at 2A resolution and refined to a final R-factor of 19.8% for 35 031 unique reflections. The enzyme is dimeric, each subunit being comprised of an N-terminal coenzyme-binding domain with a Rossmann fold, a large all-helical domain and a small C-terminal tail. The model contains 473 residues, three sulfate ions and 346 water molecules; the two best defined sulfates are found in the active site. This structure, based on improved diffraction data, is an extension of the 2.5 A, resolution model reported earlier. It has good geometry with 92% of the residues falling in the most favoured areas of the Ramachandran plot. Several unusual features are discussed: the incorporation of an alanine in place of the second conserved glycine of the dinucleotide-binding fingerprint; a duplicated five-helix motif which is unique to this enzyme; an extended water network at the dimer interface and a C-terminal tail which is incorporated within the second subunit, forming not only a major part of the dimer interface but also part of the active site.

Journal Article↗