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C A Innis

Publications and source records attributed to C A Innis.

7 recordsLinked to original sources
PubMed2001

Sequence-structure homology recognition by iterative alignment refinement and comparative modeling.

Our approach to fold recognition for the fourth critical assessment of techniques for protein structure prediction (CASP4) experiment involved the use of the FUGUE sequence-structure homology recognition program (http://www-cryst.bioc.cam.ac.uk/fugue), followed by model building. We treat models as hypotheses and examine these to determine whether they explain the available data. Our method depends heavily on environment-specific substitution tables derived from our database of structural alignments of homologous proteins (HOMSTRAD, http://www-cryst.bioc.cam.ac.uk/homstrad/). FUGUE uses these tables to incorporate structural information into profiles created from HOMSTRAD alignments that are matched against a profile created for the target from multiple sequence alignment. In addition, environment-specific substitution tables are used throughout the modeling procedure and as part of the model evaluation. Annotation of sequence alignments with JOY, to reflect local structural features, proved valuable, both for modifying hypotheses, and for rejecting predictions when the expected pattern of conservation is not observed. Our stringency in rejecting incorrect predictions led us to submit a relatively small number of models, including only a low number of false positives, resulting in a high average score.

Amino Acid Sequence↗
PubMed2000

Evolutionary trace analysis of TGF-beta and related growth factors: implications for site-directed mutagenesis.

The TGF-beta family of growth factors contains a large number of homologous proteins, grouped in several subfamilies on the basis of sequence identity. These subgroups can be combined into three broader groups of related cytokines, with marked specificities for their cellular receptors: the TGF-betas, the activins and the BMPs/GDFs. Although structural information is available for some members of the TGF-beta family, very little is known about the way in which these growth factors interact with the extra-cellular domains of their multiple cell surface receptors or with the specific protein inhibitors thought to modulate their activity. In this paper, we use the evolutionary trace method [Lichtarge et al. (1996) J. Mol. Biol., 257, 342-358] to locate two functional patches on the surface of TGF-beta-like growth factors. The first of these is centred on a conserved proline (P(36) in TGF-betas 1-3) and contains two amino acids which could account for the receptor specificity of TGF-betas (H(34) and E(35)). The second patch is located on the other side of the growth factor protomer and surrounds a hydrophobic cavity, large enough to accommodate the side chain of an aromatic residue. In addition to two conserved tryptophans at positions 30 and 32, the main protagonists in this potential binding interface are found at positions 31, 92, 93 and 98. Several mutagenesis studies have highlighted the importance of the C-terminal region of the growth factor molecule in TGF-betas and of residues in activin A equivalent to positions 31 and 94 of the TGF-betas for the binding of type II receptors to these ligands. These data, together with our improved knowledge of possible functional residues, can be used in future structure-function analysis experiments.

Amino Acid Motifs↗
PubMed1996

Patient perceptions of stereotaxic large-core breast biopsy.

RATIONALE AND OBJECTIVES: The authors evaluated the perceptions of patients who underwent stereotaxic core breast biopsy before and after the procedure. METHODS: By using a standard questionnaire, 58 patients undergoing stereotaxic core breast biopsy with a 14-gauge needle were interviewed immediately before, immediately after, and 24 hours and 5 days after the procedure. RESULTS: Discomfort recorded by patients 24 hours after core biopsy correlated with the amount of time needed before normal activities were resumed (P = .001). Only five patients (9%) indicated severe discomfort during the procedure. Patient age, number of core biopsy samples taken, and lesion depth did not correlate with level of discomfort. Fifty-five patients (95%) resumed normal activities within 24 hours. However, 41 patients (71%) had some breast bruising as many as 5 days after the procedure. Overall, patient satisfaction with care was high; 56 patients (97%) stated they would return for another biopsy in the future. CONCLUSION: The morbidity associated with stereotaxic core breast biopsy is low, although the majority of patients in this series experienced bruising lasting as long as 5 days after the procedure. Despite this, almost all patients would return for a core breast biopsy in the future, if indicated.

Activities of Daily Living↗
PubMed1993

Previous mammograms in patients with impalpable breast carcinoma: retrospective vs blinded interpretation. 1993 ARRS President's Award.

OBJECTIVE: We examined differences between blinded and retrospective reviews of screening mammograms obtained before a mammogram that resulted in the diagnosis of an impalpable breast carcinoma. MATERIALS AND METHODS: We reviewed 152 previous mammograms in 73 patients in whom impalpable breast carcinomas were subsequently detected on later mammograms. The earlier studies were interpreted in two ways: (1) blindly (without knowledge that carcinoma was subsequently detected) and (2) retrospectively (with the mammogram showing the carcinoma for comparison). The two interpretations were then compared with regard to the presence of carcinoma, recommendations for biopsy, parenchymal density, histologic characteristics of the tumor, lymph node status, and film quality. RESULTS: When we did a blinded review of the mammograms obtained before the diagnostic mammograms, the previous study was interpreted as showing evidence of carcinoma in 30 patients (41%). For the remaining 43 patients (59%), the findings of the most-recent previous mammogram were interpreted as normal or benign by the blinded reviewers; however, the retrospective reviewers thought evidence of cancer was visible in 25 of these patients (34%). Differences between blinded and retrospective interpretations were statistically significant. In patients in whom evidence of tumor was thought to be present on retrospective review but not on blinded review, the majority of mammographic abnormalities were asymmetric densities on the most-recent previous examination. This was true whether or not the retrospective reviewers thought that the mammographic finding warranted earlier biopsy. The histologic characteristics and lymph node status among patients in whom mammograms were interpreted retrospectively as showing evidence of tumor were no different from those among patients with no evidence of tumor. CONCLUSION: Our results show that impalpable breast carcinomas are frequently evident in retrospect on previous mammograms. However, because many are manifested only as an asymmetric density, these may not necessarily be true radiologic errors. Failure to detect a retrospectively visible abnormality on a screening mammogram is not necessarily negligent, and retrospective reviews do not reflect the everyday practice of screening mammography.

Awards and Prizes↗
PubMedDate not supplied

Prospective experience with a 20-gauge Tuohy needle for lumbar epidural steroid injections: Is confirmation with fluoroscopy necessary?

BACKGROUND AND OBJECTIVES: Small (20-gauge) Tuohy needles have been introduced for epidural steroid injection to optimize patient comfort and decrease the risk of spinal headache. These needles may be less reliable for indentification of the epidural space than standard 17- or 18-gauge needles because of their small size. We prospectively examined the success rate of lumbar epidural steroid placement with loss-of-resistance (LOR) technique compared with fluoroscopy confirmation. METHODS: One hundred patients without history of lumbar spine surgery were enrolled. A 20-gauge Tuohy needle was placed into the epidural space using LOR to saline. Confidence in epidural placement was recorded (Yes/No). Radiologic contrast was then injected and a fluoroscopic epidurogram interpreted by a blinded radiologist for correct placement, (Yes/No) separate from the clinical process. RESULTS: Reliability of LOR was less than our "gold standard" of fluoroscopy (P <.004). Sensitivity of LOR was 99% and specificity was 27%. Positive and negative predictive values were 92% and 75%. Increased patient age (>70 years) and male sex were associated with poor reliability of LOR (P <.05). CONCLUSIONS: In contrast to the reported 99% success rates for epidural placement of standard 17- or 18-gauge Tuohy needles, we observed a success rate of 92%. Small-gauge Tuohy needles are technically more difficult to use than larger needles and may require confirmation with fluoroscopy for correct epidural placement, especially in elderly male patients.

Aged↗
PubMedDate not supplied

Protein-protein interactions in receptor activation and intracellular signalling.

We review here signalling complexes that we have defined using X-ray analysis in our laboratory. They include growth factors and their receptors: nerve growth factor (NGF) and its hetero-hexameric 7S NGF storage complex, hepatocyte growth factor/scatter factor (HGF/SF) NK1 dimers and fibroblast growth factor (FGF1) in complex with its receptor (FGFR2) ectodomain and heparin. We also review our recent structural studies on intracellular signalling complexes, focusing on phosducin transducin GPry, CK2 protein kinase and its complexes, and the cyclin D-dependent kinase, Cdk6, bound to the cell cycle inhibitor p19INK4d. Comparing the structures of these complexes with others we show that the surface area buried in signalling interactions does not always give a good indication of the strength of the interactions. We show that conformational changes are often important in complexes with intermediate buried surface areas of 1500 to 2000 A2, such as Cdk6INK4 interactions. Some interactions involve recognition of continuous epitopes, where there is no necessity for a tertiary structure and very often the binding conformation is induced during the process of interaction, for example phosducin binding to the betagamma subunits (Gtbetagamma) of the heterotrimeric G protein transducin.

Animals↗