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Biomedical subjects

K Fogarty

Publications and source records attributed to K Fogarty.

11 recordsLinked to original sources

Prospective evaluation of antiemetic outcome following high-dose chemotherapy with hematopoietic stem cell support.

Considerable progress has been made in improving the control of chemotherapy-induced emesis. The impact of available antiemetic options for patients receiving stem cell transplants is unclear, as few prospective data have been collected. We prospectively evaluated antiemetic outcome in patients receiving stem cell transplantation over a 7-day period following the initiation of chemotherapy. The primary endpoints were the number of emetic episodes and the extent of nausea measured on a four-point scale. Eighty-two patients were evaluated. Ninety-five percent of patients had nausea during the first week of treatment; 80% had at least one emetic episode. The percentage of patients with emesis was as follows: day 1: 13%, day 2: 21%, day 3: 30%, day 4: 38%, day 5: 44%, day 6: 39%, day 7: 18%. In multivariate analysis, gender, emesis with prior chemotherapy, history of morning or motion sickness, type of transplant (auto vs allo), use of total body irradiation, or use of dexamethasone did not effect emesis control. Most patients receiving high-dose chemotherapy experience incompletely controlled emesis. Control of nausea and emesis progressively worsened with each subsequent day following initiation of chemotherapy, reaching a nadir on day 5. New treatment approaches are needed to improve emesis control in this patient population.

Adult↗

Insulin action on GLUT4 traffic visualized in single 3T3-l1 adipocytes by using ultra-fast microscopy.

A novel imaging technology, high-speed microscopy, has been used to visualize the process of GLUT4 translocation in response to insulin in single 3T3-L1 adipocytes. A key advantage of this technology is that it requires extremely low light exposure times, allowing the quasi-continuous capture of information over 20-30 min without photobleaching or photodamage. The half-time for the accumulation of GLUT4-eGFP (enhanced green fluorescent protein) at the plasma membrane in a single cell was found to be of 5-7 min at 37 degrees C. This half-time is substantially longer than that of exocytic vesicle fusion in neuroendocrine cells, suggesting that additional regulatory mechanisms are involved in the stimulation of GLUT4 translocation by insulin. Analysis of four-dimensional images (3-D over time) revealed that, in response to insulin, GLUT4-eGFP-enriched vesicles rapidly travel from the juxtanuclear region to the plasma membrane. In nontransfected adipocytes, impairment of microtubule and actin filament function inhibited insulin-stimulated glucose transport by 70 and 50%, respectively. When both filament systems were impaired insulin-stimulated glucose transport was completely inhibited. Taken together, the data suggest that the regulation of long-range motility of GLUT4-containing vesicles through the interaction with microtubule- and actin-based cytoskeletal networks plays an important role in the overall effect of insulin on GLUT4 translocation.

3T3 Cells↗

Long-term outcomes of stereotactic breast biopsies.

Stereotactic core needle biopsies (SCNBs) are accurate and relatively convenient for the patient; however, the long-term follow-up of benign results has not been reported. All patients between 1993 and 1998 undergoing SCNB at a community-based hospital were entered into a registry. Follow-up was obtained by a retrospective analysis of the charts. Biopsies were performed on 865 lesions. One hundred thirty-one (15%) were malignant, 42 (5%) were suspicious for malignancy, 687 (79%) were benign, and five (1%) were lobular carcinoma in situ. Of the 42 patients with suspicious findings 38 underwent biopsy. Ten were malignant and 28 benign. Of the 687 patients with benign pathology, 377 had follow-up available with a mean length of 1.7 years. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SCNB for benign lesions in our study are all 100 per cent. Eight lesions were worrisome and await final analysis. Of 687 patients with benign lesions 310 were lost to follow-up. This study suggests that patients with a benign diagnosis should be returned to routine mammography. These data also extend the reported follow-up to 1.7 years and establish an acceptable level of accuracy for SCNB. The lost patients remind us that follow-up is essential despite a benign diagnosis.

Biopsy, Needle↗

Visualization of single RNA transcripts in situ.

Fluorescence in situ hybridization (FISH) and digital imaging microscopy were modified to allow detection of single RNA molecules. Oligodeoxynucleotide probes were synthesized with five fluorochromes per molecule, and the light emitted by a single probe was calibrated. Points of light in exhaustively deconvolved images of hybridized cells gave fluorescent intensities and distances between probes consistent with single messenger RNA molecules. Analysis of beta-actin transcription sites after serum induction revealed synchronous and cyclical transcription from single genes. The rates of transcription initiation and termination and messenger RNA processing could be determined by positioning probes along the transcription unit. This approach extends the power of FISH to yield quantitative molecular information on a single cell.

Actins↗

Evaluation and management of sialorrhea of pregnancy with concomitant hyperemesis.

This article describes two gravid patients who presented with first-trimester sialorrhea and hyperemesis. Although excessive salivation, especially when accompanied by protracted nausea and vomiting, is an unusual occurrence, it can have serious consequences for both the mother and fetus when left untreated. Initially, phenothiazine was prescribed and later belladonna alkaloid was added separately to the two treatment regimens. In order to successfully treat the excessive salivation, it was necessary to control the nausea and vomiting. Eradication of sialorrhea and hyperemesis were effected 10 days posttreatment. For both patients, pregnancy, delivery, and postpartum intervals proceeded uneventfully. Mothers and infants remain in good health 2 years posttreatment.

Adult↗

A three-dimensional view of precursor messenger RNA metabolism within the mammalian nucleus.

A quantitative three-dimensional analysis of nuclear components involved in precursor messenger RNA metabolism was performed with a combination of fluorescence hybridization, immunofluorescence, and digital imaging microscopy. Polyadenylate [poly(A)] RNA-rich transcript domains were discrete, internal nuclear regions that formed a ventrally positioned horizontal array in monolayer cells. A dimmer, sometimes strand-like, poly(A) RNA signal was dispersed throughout the nucleoplasm. Spliceosome assembly factor SC-35 localized within the center of individual domains. These data support a nuclear model in which there is a specific topological arrangement of noncontiguous centers involved in precursor messenger RNA metabolism, from which RNA transport toward the nuclear envelope radiates.

Cell Nucleus↗

Acute leukemia. Learning disabilities following CNS irradiation.

Thirteen elementary school age children with acute leukemia who had received cranial irradiation with dosages between 1,800 and 4,800 rads a mean of 6.3 years earlier were evaluated for the presence of learning disorders. The authors utilized both psychometric and educational tests. The results were analyzed according to a graduated regressed standard score procedure and yielded the following diagnoses: mental retardation, two (15%); learning disability in reading and mathematics, two (15%); learning disability in mathematics, five (39%); no psychoeducational diagnosis, four (31%). Of the nine children (69%) who qualified for a specific psychoeducational diagnosis, only three were receiving any special educational services. The failure of a previous assessment of this same group of children at our center and of other research reports to uncover a similarly high incidence of neurodevelopmental pathology may be due to the specific tests employed or to the later onset of measurable difficulties in these patients.

Brain↗

Molecular structure and organization of filaments in single, skinned smooth muscle cells.

The contractile elements of single, skinned amphibian smooth muscle cells were resolved as fibrils containing F-actin and side-polar myosin filaments and adjacent cytoplasmic dense bodies, containing alpha-actinin and actin. The fibrils were found to be linked axially through actin filaments to the dense bodies, by electron microscopy. The arrangement of these two structures provides the essential features of a sarcomere to the contractile elements. The effect of contraction upon the movement of the dense bodies was followed dynamically by optical microscopy as a method of analyzing the organization of the contractile apparatus and resolving contractile units. Averaged over long time periods (30 to 50 seconds), the axial movements of dense bodies was uniform. The dense bodies were not simply displaced passively during contraction because the extent of radial movements averaged over the same (long) time periods were less than would be expected for the observed increases in cell diameter. Measured over short time intervals (3 to 6 seconds), the axial movement of some closely spaced dense bodies was not uniform: individual and groups of bodies moved significantly faster and slower than the mean rate of axial translocation. These shifts in coordinated and independent movements might reveal separate anisometric contractile units, or they could represent a random temporal pattern of localized activation and deactivation of small contractile elements.

Animals↗