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Biomedical subjects

R J Harris

Publications and source records attributed to R J Harris.

At least 73 records · Page 4Linked to original sources

What predicts relapse? Prospective testing of antecedent models.

Predictors of relapse to drinking were examined in a clinical sample of 122 individuals seeking outpatient treatment for alcohol problems. Drinking status and a variety of predictor variables were measured every two months for one year following presentation for treatment. In addition to pretreatment characteristics, potential antecedents of relapse were assessed at each point within five domains: (1) the occurrence of negative life events; (2) cognitive appraisal variables including self-efficacy, alcohol expectancies, and motivation for change; (3) client coping resources; (4) craving experiences; and (5) affective/mood status. Although the occurrence of adverse life events did not predict 6-month relapse, all other domains singly accounted for significant variance in drinking outcomes. Proximal antecedents (from the prior 2-month interval) significantly and substantially improved predictive power over that achieved from pretreatment characteristics alone. When analyzed jointly, these predictors accounted for a majority of variance in 6-month relapse status. A prospective test supported Marlatt's developmental model of relapse, pointing to two client factors as optimally predictive of resumed drinking: lack of coping skills and belief in the disease model of alcoholism.

Adult↗

Processing of C-terminal lysine and arginine residues of proteins isolated from mammalian cell culture.

C-terminal Lys or Arg residues whose presence was expected based on gene sequence information are often absent in proteins isolated from mammalian cell culture. This discrepancy is believed to be due to the activity of one or more basic carboxypeptidases. Internal Arg/Lys residues that become C-terminal upon proteolysis or zymogen activation, such as in the two-chain form of tissue plasminogen activator, may also be removed from the mature protein. Charge heterogeneity results when this type of processing is incomplete; such heterogeneity can be detected by isoelectric focusing or ion-exchange chromatography. The absence of C-terminal basic residues is not usually a regulatory concern, as plasma-derived proteins are often similarly processed.

Amino Acid Sequence↗

Enzymatic removal of sialic acid from human factor IX and factor X has no effect on their coagulant activity.

Factor IX and factor X have sialic acid in O-linked and N-linked oligosaccharides on their activation peptides, and a terminal sialic acid is found on a recently described O-linked tetrasaccharide at Ser-61 in the light chain of human factor IXa. In studies presented here, the potential role of sialic acid residues in mediating activity of human coagulation factors IX and X was tested after enzymatic removal of sialic acid residues. In contrast to previous reports, treatment of factor IX or factor IXa with recombinant sialidase did not decrease the rate of factor IX activation or proteolytic properties of human factor IXa. The activation rates of factor IX and desialated factor IX were indistinguishable when treated with factor XIa, with factor VIIa/tissue factor complex, and with the factor X activating enzyme from Russell's viper venom. Desialated human factor IXa showed full activity in the non-activated partial thromboplastin time assay and retained full "tenase" activity in a coupled amidolytic assay. Similar experiments with human factor X showed no detectable loss of clotting activity in the prothrombin time assay after desialation. Additionally, desialated human factor X was cleaved by the factor X activating enzyme from Russell's viper venom and intrinsic tenase at the same rate as untreated factor X when analyzed by SDS-polyacrylamide gel electrophoresis. These studies have shown that factor IX and factor X clotting activity are not dependent on sialic acid content. Further studies are needed to determine whether desialated factor IX binds to endothelial cells, and whether factors IX and X are more rapidly cleared from circulation or have altered susceptibility to proteolysis after enzymatic removal of sialic acid.

Factor IX↗

Event-related potentials in cross-modal divided attention in autism.

The behavior and event-related potentials (ERPs) of high functioning subjects with autism (Autism group) were contrasted with the results of normal controls (Control group) during a focused visual attention, a focused auditory attention and a visual/auditory divided attention task. Detecting targets by the Autism group in the cross-modal divided attention condition was more difficult (longer RTs, lower % of correct detections) than attending to one modality. However, both the Autism and Control groups performed all tasks above chance level. The slow negative wave (SNW) was the only negative component which reflected Focused vs Divided task effect in Controls, being largest to stimuli in single channel-focused attention, intermediate when attention was divided between targets of two modalities and smallest to unattended stimuli. Task effects were more evident in the positive peaks for the Autism group. No significant divided attention task effect was noted for P3b, although it was larger for attended than ignored stimuli, of normal morphology and only slightly decreased in size in the Autism group as compared to the Control group. The failure of the Autism group to modulate the slow negative wave in response to Focused/Divided/Ignored conditions in a normal manner, the presence of relatively normal morphology despite the reduced amplitude of the P3b and other positive components, together with the high level of correct target detections are discussed in the context of a selective inhibition deficit and an alternative mechanism of selective attention in autism.

Acoustic Stimulation↗

The impact of thoracoscopy on the management of pleural disease.

STUDY OBJECTIVE: To describe the diagnostic efficacy, morbidity, and patient outcome of thoracoscopy; to quantify the direct impact of thoracoscopy on clinical management; and to determine preoperative variables associated with finding malignancy at thoracoscopy to aid patient selection. DESIGN: Retrospective chart review of consecutive cases of thoracoscopy for pleural disease. SETTING: Single tertiary medical center. PATIENTS: One hundred eighty-two consecutive patients who underwent thoracoscopy for pleural disease over a 5-year period (from 1987 through 1992). MEASUREMENTS AND RESULTS: Final diagnoses were 98 (54%) malignant, 58 (32%) benign, and 26 (14%) idiopathic. Thoracoscopy had a diagnostic sensitivity of 95% for malignancy and 100% for benign disease. Malignancy was shown by thoracoscopy in 27 of 41 (66%) patients who had a preoperative nondiagnostic closed pleural biopsy, and in 24 of 35 (69%) patients who had at least 2 preoperative negative pleural cytologic specimens. Chart review by preestablished criteria showed information obtained from thoracoscopy directly influenced treatment in 155 (85%) patients. Thirty-seven (20%) patients, however, had at least one perioperative complication (15% major, 8% minor). Ten (6%) patients died during the same hospitalization in which a thoracoscopy was performed, although none died within 48 h. There was one thoracoscopy-related death. Sixty-two (34%) patients died within 6 months of thoracoscopy (death by all causes). Forty-seven (48%) patients who had intrathoracic malignancy present at thoracoscopy died within 6 months. Patients found to have malignant pleural disease by thoracoscopy were more likely to have a preoperative history of a malignancy (p = 0.001). Age more than 50 years was associated with finding malignancy at thoracoscopy (p = 0.04). A combined lymphocytic and hemorrhagic effusion was associated with malignancy (p = 0.004). Preoperative pleural data showed that idiopathic effusions had a significantly lower median lactate dehydrogenase (LDH) value (192, which was normal) compared with malignant or benign effusions. CONCLUSIONS: (1) Thoracoscopy increases yield for malignant and benign disease when thoracentesis and closed pleural biopsy are nondiagnostic. (2) Thoracoscopy directly affects clinical management in 85% of patients. (3) Significant complications can occur in patients receiving tertiary care. (4) For the evaluation of suspected malignant pleural disease, thoracoscopy has its greatest diagnostic yield in older patients who have a history of malignancy and who present with a lymphocytic, hemorrhagic, high LDH effusion.

Female↗

Treatment of an endodontic perforation with a restoration and a root coverage gingival graft.

This case report describes the treatment of a perforation on the facial surface of the maxillary right central incisor made during endodontic therapy. Treatment of this highly visible area required a creative approach to therapy. The perforation was repaired with an amalgam restoration. A connective tissue with partial thickness double pedicle graft was used to replace missing periodontal structures, cover the exposed root surface, and obscure from view, as much as possible, the amalgam restoration placed in the perforation. This unconventional therapy is offered as a possible treatment option when few or no other acceptable options exist.

Adult↗

Endoscopic management of benign airway stenosis.

Endoscopic management of benign airway stenosis is successful in the majority of patients if patients are selected properly. Predictive anatomic features have been identified that aid patient selection. Moreover, mucosal sparing techniques should be used at all times. Given its clinical effectiveness and low complication rate, endoscopic management should remain the first option for subglottic and tracheal stenosis. Endoscopic management does not preclude the use of open surgical procedures if necessary. Future studies should be directed toward refining and optimizing the endoscopic operative technique.

Adrenal Cortex Hormones↗

Attributions about spouse abuse in cases of bidirectional battering.

A particularly misunderstood type of domestic violence is the type of incident where both partners are violent, for example, where one partner is violent and the other is violent in self-defense. The present study examined third-party attributions about such battering. Subjects read a fictitious newspaper report of a domestic battering incident and then filled out rating scales about the participants and the event. The scenario described either an "asymmetric battering" incident where one party instigated the violence and was much more violent than the other, or an incident which was more of a mutual fight (symmetric battering). Both scenarios ended with one person seriously injuring the other. Each scenario had two versions, in which either the husband or the wife instigated the violence. Results showed that the person who had instigated the violence was judged more harshly and was given more responsibility for their actions in both the symmetric and asymmetric battering conditions. The less violent partner in the asymmetric conditions was judged to have more right to use force. In the symmetric battering, both parties were assigned blame.

Adult↗

Identification of succinimide sites in proteins by N-terminal sequence analysis after alkaline hydroxylamine cleavage.

Under favorable conditions, Asp or Asn residues can undergo rearrangement to a succinimide (cyclic imide), which may also serve as an intermediate for deamidation and/or isoaspartate formation. Direct identification of such succinimides by peptide mapping is hampered by their lability at neutral and alkaline pH. We determined that incubation in 2 M hydroxylamine, 0.2 M Tris buffer, pH 9, for 2 h at 45 degrees C will specifically cleave on the C-terminal side of succinimides without cleavage at Asn-Gly bonds; yields are typically approximately 50%. N-terminal sequence analysis can then be used to identify an internal sequence generated by cleavage of the succinimide, hence identifying the succinimide site.

Amino Acid Sequence↗

Generation of soluble interleukin-1 receptor from an immunoadhesin by specific cleavage.

The extracellular portion of the interleukin-1 receptor (IL-1R) is sufficient for high-affinity binding to IL-1; however, the structural basis for binding of the receptor to IL-1 is not known. To produce individual domains of IL-1 receptor for structural studies, we constructed a molecular fusion of IL-1 receptor with immunoglobulin G heavy chain that contains a protease specific sequence joining the two portions of the molecule (IL-1R-G-IgG). We introduced the hexapeptide sequence AAHY:TL (where ":" denotes the scissile bond) at the junction of the IL-1R and IgG regions, for specific cleavage by an H64A variant of subtilisin BPN' (Genenase I), an endoprotease that cleaves selectively at this sequence (Carter et al., (1989) Proteins 6, 240-248). Plasmid DNA encoding the fusion protein was used to transfect human embryonic kidney 293 cells transiently, and secreted IL-1R-G-IgG was purified from cell supernatants by protein A chromatography. The IL-1 receptor's extracellular region was then generated by enzymatic cleavage with Genenase I which was immobilized on controlled-pore glass. Incubation of IL-1R-G-IgG with immobilized Genenase I resulted in specific cleavage at the target site, as confirmed by SDS-PAGE, immunoblotting and direct sequencing of the newly generated termini. The resulting soluble IL-1R was separated from the immunoglobulin Fc cleavage product by re-chromatography on protein A. The purified, soluble IL-1R retained quantitatively the ability to bind to its ligand, IL-1 beta. This approach offers a generic means by which the extracellular region of a given type I transmembrane receptor can be expressed as an immunoadhesin, released enzymatically and then easily purified for crystallographic or ligand binding studies.

Amino Acid Sequence↗

The connective tissue with partial thickness double pedicle graft: the results of 100 consecutively-treated defects.

Obtaining predictable root coverage has been a goal of periodontal therapy for some time. The connective tissue with partial thickness double pedicle graft has been shown to produce predictable esthetic root coverage. The purpose of this study was to examine the results of the surgical technique on 100 consecutively treated defects. The procedure produced a mean root coverage of 97.7%. Root coverage of 100% was obtained 89% of the time. With this technique, esthetic root coverage can be accomplished in a predictable manner. Additionally, it was the intent of this study to examine whether or not certain factors could be associated with root coverage results. Factors that could be associated with root coverage success or lack of success included: size of the pedicle, previous free gingival graft, and plaque control during the postoperative period. Factors that did not appear to be related to root coverage included: history of smoking (heavy or light), defect width, defect depth, history of snuff use, history of orthodontics, tooth type treated, number of defects treated, age, preoperative bleeding on probing, preoperative plaque present, esthetic concerns of the patient, and surgical experience of the operator. Additionally, attached gingiva levels were not a factor if the areas had not been treated with a free gingival graft.

Adolescent↗

Thoracic mesothelioma associated with abdominal mesenteric panniculitis.

Mesenteric panniculitis (MP) is characterized by an abdominal inflammatory reaction and mesenteric fat necrosis. Clinically, MP manifests as recurrent abdominal pain, pyrexia, and space-occupying peritoneal masses. We report a patient with MP, severe enough to require immunosuppressant treatment, who developed a recurrent pleural effusion. Malignant mesothelioma was identified in the pleural space 3 yr after initial pleural investigation. This case is the second report of pleural effusion associated with MP. It is the first report in which thoracic mesothelioma and MP occurred together. MP has been associated with other malignancies.

Adult↗

The coronally positioned pedicle graft with inlaid margins: a predictable method of obtaining root coverage of shallow defects.

There are several techniques that will predictably cover exposed root surfaces; however, most techniques are generally used to treat larger recession areas or sites with inadequate keratinized tissue. The purpose of this study is to evaluate the use of the coronally positioned pedicle graft with inlaid margins in the treatment of shallow recession areas. Utilizing the described technique, 20 isolated Class I defects were treated. Complete root coverage was obtained 95% of the time; the mean root coverage was 98.8%. The procedure resulted in a decrease in sensitivity, the final color and tissue contours of the grafts were excellent, and all patients were satisfied with the results. The coronally positioned pedicle graft with inlaid margins is a simple and predictable method to cover exposed root surfaces in shallow recession areas.

Adult↗

Identification and structural analysis of the tetrasaccharide NeuAc alpha(2-->6)Gal beta(1-->4)GlcNAc beta(1-->3)Fuc alpha 1-->O-linked to serine 61 of human factor IX.

O-Linked fucose has been found attached to Thr/Ser residues within the sequence Cys-X-X-Gly-Gly-Thr/Ser-Cys in the N-terminal EGF domains of several coagulation/fibrinolytic proteins. Carbohydrate composition and mass spectrometric analyses of tryptic and thermolytic peptides containing the corresponding site (Ser-61) in the first EGF domain of human factor IX indicated the presence of a tetrasaccharide containing one residue each of sialic acid, galactose, N-acetylglucosamine, and fucose. The Ser-61 tetrasaccharide was not susceptible to alpha-fucosidase digestion. Fragments generated during mass spectrometric analysis indicated that fucose was the attachment sugar residue. The involvement of fucose in the carbohydrate-peptide linkage was confirmed by two-dimensional 1H NMR spectroscopic analysis of the glycopeptide containing factor IX residues 57-65. The complete structure of the tetrasaccharide was obtained by methylation analysis and two-dimensional 1H TOCSY and ROESY experiments as NeuAc alpha(2-->6)Gal beta(1-->4)GlcNAc beta(1-->3)Fuc alpha 1-->O-Ser61.

Amino Acid Sequence↗

Glycosylation pattern and disulfide assignments of recombinant human differentiation-stimulating factor.

This report describes the post-translational modifications of recombinant human differentiation-stimulating factor, a 180-residue glycoprotein that is secreted from transfected Chinese hamster ovary cells. Peptide peptides containing six potential N-glycosylation sites were analyzed to determine that Asn residues 9, 34, 63, 73, 96, and 116 were utilized. Additional peptides, generated by tryptic digestion of peptic fragments, allowed the assignments of three intrachain disulfide bonds (Cys-18 to Cys-131, Cys-12 to Cys-134, and Cys-60 to Cys-163).

Amino Acid Sequence↗