Biomedical subjects

L Harris

Publications and source records attributed to L Harris.

At least 19 recordsLinked to original sources

PubMed1997

The Genome Sequence DataBase version 1.0 (GSDB): from low pass sequences to complete genomes.

The Genome Sequence DataBase (GSDB) has completed its conversion to an improved relational database. The new database, GSDB 1.0, is fully operational and publicly available. Data contributions, including both original sequence submissions and community annotation, are being accomplished through the use of a graphical client-server interface tool, the GSDB Annotator, and via GIO (GSDB Input/Output) files. Data retrieval services are being provided through a new Web Query Tool and direct SQL. All methods of data contribution and data retrieval fully support the new data types that have been incorporated into GSDB, including discontiguous sequences, multiple sequence alignments, and community annotation.

Animals↗

PubMed1997

Arrhythmia and mortality after the Mustard procedure: a 30-year single-center experience.

OBJECTIVES: Our purpose was to assess the risk factors for late mortality, loss of sinus rhythm and atrial flutter after the Mustard operation. BACKGROUND: The Mustard operation provides correction of cyanosis with low surgical risk in transposition of the great vessels. However, right ventricular failure, loss of sinus rhythm, atrial flutter and death are frequent long-term complications. METHODS: Records of 534 children who underwent the Mustard operation at a single center since 1962 were reviewed for demographic, anatomic, electrocardiographic and physiologic predictors and outcomes. RESULTS: There were 52 early deaths (9.7%). Survival analysis was undertaken for 478 early survivors with a mean follow-up interval of 11.6 +/- 7.2 years. There were 77 late deaths (16.1%), with sudden death (n = 31) the most frequent cause. Survival estimates were 89% at 5 years and 76% at 20 years of age. Risk factors were an earlier date of operation, operative period arrhythmia and an associated ventricular septal defect. Risk (hazard) of late death declined in the first decade, with further peaks in the second decade. Sinus rhythm was present in 77% at 5 years and 40% at 20 years. Loss of sinus rhythm was associated with previous septectomy, postoperative bradycardia and late atrial flutter. Freedom from atrial flutter was 92% at 5 years and 73% at 20 years of age. Risk factors for atrial flutter were the occurrence of perioperative bradyarrhythmia, reoperation and loss of sinus rhythm during follow-up. Risk of atrial flutter demonstrates a late increase. CONCLUSIONS: Ongoing loss of sinus rhythm and late peaks in the risk of atrial flutter and death necessitate continued follow-up.

Arrhythmias, Cardiac↗

PubMed1997

Small-dose propofol by continuous infusion does not prevent postoperative vomiting in females undergoing outpatient laparoscopy.

This study was designed to test the hypothesis that there is a direct prophylactic antiemetic effect of small-dose propofol given by continuous infusion. Sixty female patients undergoing outpatient laparoscopy under general anesthesia were randomized to receive, in a double-blind fashion, either a bolus of 0.1 mg/kg followed by a constant infusion of 1 mg.kg-1.h-1 of propofol or an equivalent volume of 10% Intralipid (placebo) beginning 30 min before induction of anesthesia and continuing until discharge from Stage I postanesthesia care unit (PACU). Anesthesia was induced and maintained in a standard fashion in all patients. The number of emetic episodes before and after discharge from PACU, nausea scores (11-point numerical scale), and time to discharge were evaluated. No significant differences between Intralipid and propofol were found for any of the outcome variables tested. While small-dose propofol is an effective adjuvant in reducing chemotherapy-induced emesis, we were unable to demonstrate any beneficial effect of propofol in reducing postoperative nausea and vomiting when used as the sole prophylactic medication in this patient population. Propofol may have a synergistic effect when administered with other antiemetics, or the specific antiemetic effect of propofol, if it exists, may be dose-dependent and the dose used in this study was below the efficacy threshold.

Adolescent↗

PubMed1997

Analysis of whole-cell fatty acid profiles of verotoxigenic Escherichia coli and Salmonella enteritidis with the microbial identification system.

Differentiation of strains within bacterial species, based on gas chromatographic analysis of whole-cell fatty acid profiles, was assessed with 115 strains of verotoxigenic Escherichia coli and 315 strains of Salmonella enteritidis. Fatty acid-based subgroups within each of the two species were generated. Variability of fatty acid profiles observed in repeat preparations from the same strain approached that observed between subgroups, limiting the usefulness of using fatty acid profiles to subgroup verotoxigenic E. coli and S. enteritidis strains.

Bacterial Toxins↗

PubMed1996

Supratentorial primitive neuroectodermal tumors in children.

A retrospective review of 36 children diagnosed with a supratentorial primitive neuroectodermal tumor (PNET) at the Hospital for Sick Children was performed for the period 1970-1995. All children but one received their initial treatment at our institution. There were 18 males and 18 females and the median age at diagnosis was 35 months. Twenty-two PNETs were lobar, 3 were deep in the hemisphere, and 10 were located in the pineal region. One child presented with intracranial leptomeningeal disseminated disease. The tumors were mostly undifferentiated although 22 had some evidence of differentiation along one or more neuroepithelial lines. Five children had a biopsy, 24 had subtotal resection, and 7 had gross total resection. Twenty-six children had adjuvant radiotherapy and 13 had chemotherapy. At last follow-up 30 patients were dead and 6 were alive. The median survival was 23 months and the 2, 3, and 5 year survivals were 50%, 34%, and 18% respectively. All of the survivors received craniospinal radiation and 4 received chemotherapy. There was a statistically significantly worse survival in young children. There was a trend to better survival in children treated since 1984, and in children undergoing gross total resection. Because of the extremely poor survival, we recommended that all children undergo gross total resection followed by chemotherapy. For children older than 3 years of age craniospinal radiation should also be given.

Antineoplastic Agents↗

PubMed1996

The significance of heregulin in breast cancer tumor progression and drug resistance.

The erbB-2 receptor plays an important role in the prognosis of breast cancer and is expressed at high levels in nearly 30% of tumors in breast cancer patients. While evidence accumulates to support the relationship between erbB-2 overexpression and poor overall survival in human breast cancer, understanding of the biological consequence(s) of erbB-2 overexpression remains elusive. The discovery of heregulin has allowed us to identify a number of related but distinct biological endpoints which appear responsive to signal transduction through the erbB-2/4 receptor. These endpoints of growth, invasiveness, and differentiation have clear implications for the emergence, maintenance, and/or control of malignancy, and represent established endpoints in the assessment of malignant progression in human breast cancer. Preliminary studies in vitro have shown that heregulin induces a biphasic growth effect on cells with erbB-2 overexpression. Interestingly, we observed that expression of heregulin correlates with a more aggressive/invasive, vimentin-positive phenotype in breast cancer cells lines. Therefore, we have postulated that heregulin is involved in breast cancer tumor progression. We have shown that heregulin induces in vitro chemoinvasion and chemotaxis of breast cancer cells as well as growth in an anchorage dependent and independent manner. Interestingly, a heregulin neutralizing antibody inhibits chemotaxis and results in cell growth inhibition and blockade of the invasive phenotype. Strikingly, genetically engineered cells which constitutively express heregulin demonstrate critical phenotypic changes that are associated with a more aggressive phenotype. Specifically, these cells are no longer dependent on estrogen for growth and are resistant to tamoxifen in vitro and in vivo, and moreover these cells metastasize to lymph nodes in athymic nude mice. These tumors appear to have lost bcl-2 expression as compared with the control tumors. In addition, presumably by activation/regulation of topoisomerase II, the heregulin-transfected cells become exquisitely sensitive to doxorubicin and VP-16. Clearly, mechanistic aspects of the erbB-2/4 and heregulin interaction need to be understood from a therapeutic standpoint which could provide additional insights into synergistic treatments for certain patients, or improve treatment regimens for a large number of women. The study of heregulin and its co-expression with erbB-2/4 receptor and the assessment of its involvement in the progression from the in situ stage of breast tumors to the invasive one will additionally increase the relevance of heregulin as a prognostic/diagnostic factor. We believe that our studies provide new insights into breast cancer diagnosis, prognosis, and treatment.

Breast Neoplasms↗

PubMed1996

Effect of rice cereal feedings on bone mineralization and calcium homeostasis in cow milk formula fed infants.

OBJECTIVE: We conducted a prospective randomized, single-blinded clinical trial to test the hypothesis that intake of formula plus cereals between the ages of 16 and 26 weeks postnatally (as compared to formula alone) would lead to lower bone mineral content (BMC), higher parathyroid hormone (PTH) concentration, lower serum calcium (Ca), magnesium (Mg) and osteocalcin (OC); and increased continuous night sleep. METHODS: At 16 weeks postnatally, 41 healthy, term infants were randomized to formula alone or formula and cereal. RESULTS: We found no significant differences in growth or sleep pattern, nor in BMC between groups. Serum PTH concentration was significantly increased in the cereal group at 26 weeks. CONCLUSION: We speculate that the increase in PTH is due to relative Ca deficiency or is responsive to increased phosphate load in the cereal group.

Animals↗

PubMed1996

Autogenous soft-tissue procedures and osseointegrated alloplastic reconstruction: their role in the treatment of complex craniofacial defects.

Between 1990 and 1994, twenty-seven patients with extraoral craniofacial defects were treated at the Craniofacial Osseointegration and Maxillofacial Prosthetic Rehabilitation Unit in Edmonton. Fourteen patients required management by a combination of alloplastic and autogenous techniques to optimize their reconstructive result. Autogenous soft-tissue procedures were performed almost twice as often in patients whose deformity was the result of trauma. Autogenous soft-tissue procedures included soft-tissue expansion, static facial slings, free and pedicled vascularized bone grafts, eyebrow reconstruction, brow lifts, and scar revisions. These reconstructive procedures are illustrated in three cases.

Adult↗

PubMed1996

A selective and differential medium for Vibrio harveyi.

A new medium, termed Vibrio harveyi agar, has been developed for the isolation and enumeration of V. harveyi. It is possible to differentiate V. harveyi colonies from the colonies of strains representing 15 other Vibrio species with this medium. This medium has been shown to inhibit the growth of two strains of marine Pseudomonas spp. and two strains of marine Flavobacterium spp. but to allow the growth of Photobacterium strains. Colonies displaying typical V. harveyi morphology were isolated from the larval rearing water of a commercial prawn hatchery with V. harveyi agar as a primary isolation medium and were positively identified, by conventional tests, as V. harveyi. This agar displays great potential as a primary isolation medium and offers significant advantages over thiosulfate-citrate-bile salts-sucrose agar as a medium for differentiating V. harveyi from other marine and estuarine Vibrio species.

Culture Media↗

PubMed1996

The role of primary chemotherapy in early breast cancer.

Primary chemotherapy was first attempted in the early 1970s in an attempt to improve local control and survival in patients with large breast tumors. While it is now clear that primary chemotherapy can achieve high response rates and allow more conservative surgery, it is less apparent if survival is improved in these patients. It is logical, then, to consider moving this form of treatment to an earlier stage of disease in which the probability of resistant clones is less in patients with lower tumor burden. Many questions still remain unanswered in the evaluation of the role of primary chemotherapy in the treatment of early breast cancer: Is the best method of diagnosis fine needle aspiration or incisional biopsy? What diagnostic tests are important before chemotherapy? Can better conservative local treatment be achieved using the primary modality of chemotherapy? Is local control, disease response, and/or survival improved by using chemotherapy before local measures? Several important studies have been performed in the treatment of early stage disease with primary chemotherapy and will be discussed with these questions in mind. In addition, investigation of markers that predict response to chemotherapy may help us better select patients who would benefit from primary chemotherapy. Those patients who are determined to have a poorer prognosis would be candidates for novel investigational treatments.

Antineoplastic Agents↗

PubMed1995

Efficient plasmid DNA replication in Xenopus egg extracts does not depend on prior chromatin assembly.

Small plasmids replicate efficiently in unfertilized Xenopus eggs provided they are injected before rather than after activation of the cell cycle. Here we use Xenopus egg extracts to test the hypothesis that efficient replication results from chromatin assembly prior to activation giving preloaded plasmids a head start toward the formation of a replicating pseudonucleus (Sanchez, J.A., Marek, D., and Wangh, L.J. (1992) J. Cell Sci. 103, 907-918). As in ovum, plasmid DNA preincubated in unactivated egg cytoplasmcytostatic factor extracts) replicate more efficiently after extract activation than does the same DNA added to the same extract after activation. Unlike in ovum, however, plasmids that replicate efficiently in vitro do not assemble into chromatin during preincubation and become topologically knotted instead. But even DNA knotting does not explain subsequent efficient replication. Also, plasmids preassembled into chromatin in vitro do not replicate efficiently in activated egg cytoplasm unless first preincubated in a CSF extract. We conclude that unactivated eggs contain replication-enhancing activities that can act independently of plasmid chromatin assembly and DNA topology. These postulated "preloading" factor(s) may be related to licensing factor, an activity that controls initiation of DNA replication in eukaryotic cells. The experimental conditions described here will permit characterization of preloading/licensing factor(s) in the context of a small plasmid substrate.

Animals↗

PubMed1995

Conformational similarity and systematic displacement of complementarity determining region loops in high resolution antibody x-ray structures.

Comparison of seven high resolution x-ray structures shows that the conformations of canonical complementarity determining region (CDR) loops, which are shared by these antibodies, are very similar. However, large spatial displacements (up to 2.7 A) of the essentially identical CDR loops become evident when the antibody beta-sheet frameworks, to which the loops are attached, are least-squares superposed. The loop displacements follow, and amplify, small positional differences in framework/loop splice points. Intradomain structural variability and, to a lesser extent, domain-domain orientation appear to cause the observed loop divergences. The results suggest that the selection of framework regions for loop grafting procedures is more critical than previously thought.

Amino Acid Sequence↗

PubMed1995

Coronary sinus morphology in patients with atrioventricular junctional reentry tachycardia and other supraventricular tachyarrhythmias.

BACKGROUND: Coronary sinus access by electrode catheters is easier in patients with atrioventricular junctional reentry tachycardia (AVJRT) than in patients with other supraventricular tachyarrhythmias. The reason for this has not been addressed. METHODS AND RESULTS: The size and shape of the proximal coronary sinus were measured in 15 patients with AVJRT and 14 control subjects after angiographic visualization. Coronary sinus dimensions, morphology, and angle of origin from the right atrium were measured. The proximal coronary sinus in patients with AVJRT was larger than in the control population. The mean ostium diameter was 12.2 +/- 2 mm compared with control dimensions of 8.5 +/- 1.5 mm, P = .00001. At a distance of 5 mm from the ostium, the coronary sinus measured 10.2 +/- 1.8 mm compared with 8.1 +/- 1.9 mm, P = .007. The dilatation persisted 10 mm into the coronary sinus, with a measurement of 9 +/- 1.4 mm compared with 7.6 +/- 2 mm, P = .04. In 73% of AVJRT patients, the proximal coronary sinus had the appearance of a wind sock. This morphology was seen only in 7% of control patients, in whom the coronary sinus was tubular (in 93%). There was considerable interindividual variability in the angle of origin. CONCLUSIONS: The proximal coronary sinus in patients with AVJRT was significantly different from a control population. The ostium was 44% larger and remained more dilated to at least 10 mm from the ostium. The appearance was like a wind sock in AVJRT patients and tubular in the control patients. These findings may have important implications for arrhythmia pathogenesis in such patients.

Adolescent↗

PubMed1995

Female adolescents of alcohol misusers: disordered eating features.

Studies show that children of alcohol-abusing parents constitute an at-risk population. This study attempted to understand the impact of parental alcohol misuse on the disordered eating behaviors of their female adolescent children, based on a sample of 532 teenagers from alcohol-misusing parents in Minnesota. These female adolescents had significantly higher prevalence rates of all the seven eating disordered symptoms that were studied. The study also identified a few protective factors: Those who did not develop any of the disordered eating symptoms were more satisfied with their present weight. Further, they worried less about abuse from parents and perceived that their school personnel cared about them.

Adolescent↗

PubMed1995

Profiles for the analysis of immunoglobulin sequences: comparison of V gene subgroups.

A format for the structure-oriented analysis of immunoglobulin (Ig) variable region sequences is presented and applied to generate sequence profiles for comparison of heavy- and light-chain subgroups. The profile allows simultaneous evaluation of sequences and structural information and can be used for a number of different applications.

Amino Acid Sequence↗

PubMed1995

Interaction between erbB-receptors and heregulin in breast cancer tumor progression and drug resistance.

The type I growth factor receptor family is increasingly recognized as important in the development and maintenance of breast cancer. The family currently consists of four closely related members: the epidermal growth factor receptor (EGF-R/erbB-1), erbB-2, erbB-3 and erbB-4. Putative ligands which bind directly to or indirectly activate erbB-2/3/4 have been characterized recently. This still growing family of EGF-related growth factors includes gp30, its homolog heregulin (HRG), the rat homolog neu differentiation factor (NDF), glial growth factors (GLIA), ARIA and a 50 kDa factor from COLO 16 cells. The understanding of the function, biology and interactions of these growth factor receptors and their ligands will have far-reaching implications for the prognosis and treatment of breast cancer. This review focuses on advances and future directions for further investigations intended to clarify the mechanism and significance of erbB/ligand interactions in breast cancer.

Animals↗

PubMed1995

Endocardial mapping of ventricular tachycardia in the intact human ventricle. III. Evidence of multiuse reentry with spontaneous and induced block in portions of reentrant path complex.

OBJECTIVES: This study was conducted to characterize the functional nature of the reentrant tract responsible for ventricular tachycardia due to ischemic heart disease. BACKGROUND: A zone of slow conduction forming the return path is though to form a critical component of the reentrant mechanism in ventricular tachycardia. Despite its importance, detailed knowledge of the return path is rare in clinical studies. METHODS: Multielectrode arrays were used intraoperatively to obtain unipolar and high gain bipolar recordings of left ventricular endocardium in patients undergoing map-directed surgical ablation of ventricular tachycardia. A total of 224 local electrograms were analyzed for each tachycardia. RESULTS: Of 10 consecutive patients undergoing intraoperative cardiac mapping, detailed recording of the return tracts of eight ventricular tachycardias were obtained in three patients. The recordings demonstrated that return tracts can be complex and extensive, with multiple paths of entry and exit. Potential and actual alternate paths were observed. Spontaneous and induced block occurred within portions of the complex. Intermittent block in one of two paths of entry resulted in intermittent cycle length changes of the tachycardia without a change in configuration. Block in one exit path resulted in a shift to alternative exit paths, with dramatic changes in ventricular activation and tachycardia configuration. Termination of the tachycardia could result from block close to the entrant or exit portion of the return tract. Different tachycardias were seen to share common portions of a return tract. CONCLUSIONS: These observations enlarge and extend our knowledge of the functional repertoire of complex reentrant tracts that occur in infarct-related ventricular tachycardia. The use of common portions of a reentrant tract by several tachycardias is confirmed. Utilization of alternate pathways can account for changes in configuration and cycle length. Spontaneous and induced block can occur at points of entry and exit in a reentrant tract and may identify optimal targets for ablation attempts. Further advances will require greater emphasis on diastolic activation mapping.

Cardiac Pacing, Artificial↗

PubMed1995

Ventricular tachycardia in ischaemic heart disease: insights into the mechanisms from cardiac mapping and implications for patient management.

Ventricular tachycardia following myocardial infarction in man is thought to be due to a reentrant mechanism, with a zone of slow conduction forming the critical element of the return pathway. Cardiac mapping has helped characterize the anatomical and functional nature of reentrant pathways, and is used to direct antiarrhythmic surgery and catheter ablation. This review will explore how cardiac mapping has contributed to our understanding of reentrant ventricular tachycardia. The role of diastolic mapping will be emphasised, and the implications for future management of ventricular tachycardia discussed.

Body Surface Potential Mapping↗