Biomedical subjects

B Cutler

Publications and source records attributed to B Cutler.

At least 19 recordsLinked to original sources

PubMed1999

Real-time imaging of the dynamics of secretory granules in growth cones.

Secretory granules containing a hybrid protein consisting of the regulated secretory protein tissue plasminogen activator and an enhanced form of green fluorescent protein were tracked at high spatial resolution in growth cones of differentiated PC12 cells. Tracking shows that granules, unlike synaptic vesicles, generally are mobile in growth cones. Quantitative analysis of trajectories generated by granules revealed two dominant modes of motion: diffusive and directed. Diffusive motion was observed primarily in central and peripheral parts of growth cones, where most granules diffused two to four orders of magnitude more slowly than comparably sized spheres in dilute solution. Directed motion was observed primarily in proximal parts of growth cones, where a subset of granules underwent rapid, directed motion at average speeds comparable to those observed for granules in neurites. This high-resolution view of the dynamics of secretory granules in growth cones provides insight into granule organization and release at nerve terminals. In particular, the mobility of granules suggests that granules, unlike synaptic vesicles, are not tethered stably to cytoskeletal structures in nerve terminals. Moreover, the slow diffusive nature of this mobility suggests that secretory responses involving centrally distributed granules in growth cones will occur slowly, on a time scale of minutes or longer.

Animals↗

PubMed1998

Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease.

PURPOSE: This study evaluated the effects of cilostazol on walking distances in patients with intermittent claudication (IC) caused by peripheral arterial occlusive disease. METHODS: The study was a multicenter, randomized, double-blind, placebo-controlled trial. Two hundred thirty-nine patients with IC were randomly assigned to receive cilostazol (100 mg b.i.d.) or a placebo for 16 weeks. All patients underwent serial, variable-grade, constant-speed treadmill testing. Absolute claudication distance (ACD), assessed at the end of the 12-hour dosing interval (trough), was the primary end point. Secondary end points included ACD assessed 3 to 4 hours after dosing (peak) and initial claudication distances (trough and peak). Functional status measures, including the Medical Outcomes Scale (SF-36) and Walking Impairment Questionnaire, were used to assess subjective changes over the 16-week treatment period. Ankle-brachial indexes were calculated from Doppler-measured systolic pressures at every visit with treadmill testing. RESULTS: Patients treated with cilostazol demonstrated significant improvements over the placebo patients in ACD at all three time points tested after baseline (weeks 8, 12, and 16). Peak treadmill testing at weeks 8 and 12 also showed significant improvement in walking distances for cilostazol-treated patients over placebo-treated patients. At week 16, patients in the cilostazol group had a 96.4-meter (47%) increase in ACD compared with 31.4 meters (12.9%) for the placebo group (p < 0.001). In the SF-36, significant improvement was observed in the physical component subscale and the composite physical component score. In the Walking Impairment Questionnaire, improvements were significant in patient reports of walking speed and specific measures of walking difficulty. Ankle-brachial indexes improved in the cilostazol group (0.64 +/- 0.02 to 0.70 +/- 0.02) compared with the placebo group (0.68 +/- 0.02 to 0.69 +/- 0.02) (p < 0.0125). The most frequent adverse events were headache, abnormal stools (e.g. loose stools), diarrhea, and dizziness. CONCLUSIONS: Cilostazol significantly increased ACD at all measured time points and initial claudication distances at most time points. This agent may represent a new treatment option for patients with intermittent claudication.

Cilostazol↗

PubMed1998

Real-time imaging of the axonal transport of granules containing a tissue plasminogen activator/green fluorescent protein hybrid.

A hybrid protein, tPA/GFP, consisting of rat tissue plasminogen activator (tPA) and green fluorescent protein (GFP) was expressed in PC12 cells and used to study the distribution, secretory behavior, and dynamics of secretory granules containing tPA in living cells with a neuronal phenotype. High-resolution images demonstrate that tPA/GFP has a growth cone-biased distribution in differentiated cells and that tPA/GFP is transported in granules of the regulated secretory pathway that colocalize with granules containing secretogranin II. Time-lapse images of secretion reveal that secretagogues induce substantial loss of cellular tPA/GFP fluorescence, most importantly from growth cones. Time-lapse images of the axonal transport of granules containing tPA/GFP reveal a surprising complexity to granule dynamics. Some granules undergo canonical fast axonal transport; others move somewhat more slowly, especially in highly fluorescent neurites. Most strikingly, granules traffic bidirectionally along neurites to an extent that depends on granule accumulation, and individual granules can reverse their direction of motion. The retrograde component of this bidirectional transport may help to maintain cellular homeostasis by transporting excess tPA/GFP back toward the cell body. The results presented here provide a novel view of the axonal transport of secretory granules. In addition, the results suggest that tPA is targeted for regulated secretion from growth cones of differentiated cells, strategically positioning tPA to degrade extracellular barriers or to activate other barrier-degrading proteases during axonal elongation.

Animals↗

PubMed1997

Chromatin dynamics in interphase nuclei and its implications for nuclear structure.

Translational dynamics of chromatin in interphase nuclei of living Swiss 3T3 and HeLa cells was studied using fluorescence microscopy and fluorescence recovery after photobleaching. Chromatin was fluorescently labeled using dihydroethidium, a membrane-permeant derivative of ethidium bromide. After labeling, a laser was used to bleach small (approximately 0.4 microm radius) spots in the heterochromatin and euchromatin of cells of both types. These spots were observed to persist for >1 h, implying that interphase chromatin is immobile over distance scales >/=0.4 microm. Over very short times (<1 s), a partial fluorescence recovery within the spots was observed. This partial recovery is attributed to independent dye motion, based on comparison with results obtained using ethidium homodimer-1, which binds essentially irreversibly to nucleic acids. The immobility observed here is consistent with chromosome confinement to domains in interphase nuclei. This immobility may reflect motion-impeding steric interactions that arise in the highly concentrated nuclear milieu or outright attachment of the chromatin to underlying nuclear substructures, such as nucleoli, the nuclear lamina, or the nuclear matrix.

3T3 Cells↗

PubMed1992

Flexion characteristics of four-unit fixed partial denture frameworks using holographic interferometry.

Flexion of a metal/ceramic fixed partial denture (FPD) framework under function can cause fracture of the porcelain or deterioration of the cement seal. This study evaluated the flexion under compressive load of a four-unit mandibular FPD replacing the second premolar and the first molar. Testing was accomplished with elapsed time holographic interferometry, using 39 porcelain fused-to-metal frameworks cast with a silver-palladium alloy. The results demonstrated that solder joints at the junction of the premolar and molar pontics flexed under a reduced compressive load and exhibited a higher failure rate than other connector designs.

Analysis of Variance↗

PubMed1991

Results of a multicenter study of the modified hook-titanium Greenfield filter.

Initial efforts to modify the stainless steel Greenfield filter for percutaneous insertion led to development of a titanium Greenfield filter, which could be inserted by use of a 12F carrier. This device functioned well as a filter but had an unacceptable 30% rate of migration, tilting, and penetration. Therefore a titanium Greenfield filter with modified hooks was developed and has been tested in 186 patients at 10 institutions. Successful placement occurred in 181 (97%); placement of the remainder was precluded by unfavorable anatomy. A contraindication to anticoagulation was the most frequent indication for insertion (75%). All but two were inserted percutaneously, predominantly via the right femoral vein (70%). Initial incomplete opening was seen in four patients (2%), which was corrected by guide wire manipulation and asymmetry of the legs in 10 (5.4%). Insertion site hematoma occurred in one patient, and apical penetration of the cava during insertion occurred in a second patient. Both events were without sequelae. Follow-up examinations were performed at 30 days at which time 35 deaths had occurred. Recurrent embolism was suspected in six patients (3%) and two of three deaths were confirmed by autopsy. Filter movement greater than 9 mm was seen in 13 patients, (11%) and increase in base diameter greater than or equal to 5 mm was seen in 17 patients (14%). CT scanning showed evidence of caval penetration in only one patient (0.8%). Insertion site venous thrombosis was seen in 4/46 (8.7%) patients screened. The modified hook titanium Greenfield filter is inserted percutaneously or operatively through a sheath, eliminating concern for misplacement from premature discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

Serum transferrin receptor for the detection of iron deficiency in pregnancy.

Measurements of circulating transferrin receptor provide a sensitive quantitative index of tissue iron deficiency in otherwise healthy subjects. This investigation was undertaken to examine the diagnostic utility of this new iron index in pregnancy. A battery of iron-related measurements, including serum transferrin receptor concentrations, was performed on 176 women in third-trimester pregnancy who were attending a university prenatal clinic. The mean receptor concentration of 5.96 +/- 2.37 mg/L (+/- 1 SD) did not differ significantly from concentrations in nonpregnant individuals and the frequency distributions were likewise comparable. Elevations in serum receptor greater than 8.5 mg/L occurred only in women with depleted iron stores defined by serum ferritin concentrations. Abnormal concentrations were found in 11 of 13 women with overt iron-deficiency anemia. Our findings indicate that serum receptor concentrations are not influenced by pregnancy per se and are a sensitive index of iron deficiency. By combining serum receptor and serum ferritin measurements, the entire spectrum of iron status in pregnancy can be assessed.

Adolescent↗

PubMed1991

Ultrastructural localization of blood group antigen A in normal and neoplastic urothelium.

The subcellular distribution of the blood group antigen A in the transitional epithelium of the urinary tract and its neoplastic growths was studied using transmission immuno-electronmicroscopy. Sixty-five tissue specimens from 50 blood group A1 patients were processed according to an immunogold procedure which was optimized for preservation of both antigen and ultrastructure. The reactions were stronger in the glycocalyx of the luminal surfaces and at the interdigitating cytoplasmic processes of the cells. In the intracellular compartment the reactions were associated with tubulovesicular membrane-bound structures and with the Golgi complexes. Secretory products, intra- or extra-cellular, were also positive. The greatest variability was noted in the cell surface reactions, which were positive in 88% of normal but only 41% of neoplastic urothelial specimens. An inverse correlation was found between malignant behaviour and cell surface, but not intracellular, reactions. We conclude that, in transitional cell carcinomas, there is a quantitative defect in the processing of substance A which affects predominantly the cell surface component and may involve either the transport-insertion steps, the plasma membrane-associated glycosyltransferases or internalization of blood group antigen A.

ABO Blood-Group System↗

PubMed1990