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Biomedical subjects

J L Williams

Publications and source records attributed to J L Williams.

At least 145 records · Page 8Linked to original sources
PubMed1996

Novel alterations in CDK1/cyclin B1 kinase complex formation occur during the acquisition of a polyploid DNA content.

The pathways that regulate the S-phase events associated with the control of DNA replication are poorly understood. The bone marrow megakaryocytes are unique in that they leave the diploid (2C) state to differentiate, synthesizing 4 to 64 times the normal DNA content within a single nucleus, a process known as endomitosis. Human erythroleukemia (HEL) cells model this process, becoming polyploid during phorbol diester-induced megakaryocyte differentiation. The mitotic arrest occurring in these polyploid cells involves novel alterations in the cdk1/cyclin B1 complex: a marked reduction in cdk1 protein levels, and an elevated and sustained expression of cyclin B1. Endomitotic cells thus lack cdk1/cyclin B1-associated H1-histone kinase activity. Constitutive over-expression of cdk1 in endomitotic cells failed to re-initiate normal mitotic events even though cdk1 was present in a 10-fold excess. This was due to an inability of cyclin-B1 to physically associate with cdk1. Nonetheless, endomitotic cyclin B1 possesses immunoprecipitable H1-histone kinase activity, and specifically translocates to the nucleus. We conclude that mitosis is abrogated during endomitosis due to the absence of cdk1 and the failure to form M-phase promoting factor, resulting in a disassociation of mitosis from the completion of S-phase. Further studies on cyclin and its interacting proteins should be informative in understanding endomitosis and cell cycle control.

CDC2 Protein Kinase↗
PubMed1996

Mottle on computed radiographs of the chest in pediatric patients.

PURPOSE: To investigate the relationship between radiation exposure and perceived mottle at bedside pediatric chest examinations performed with screen-film and computed radiographic techniques. MATERIALS AND METHODS: In a pediatric intensive care unit, chest radiographs were obtained with both computed radiography (60 radiographs) and a 600-speed screen-film system (14 radiographs). The relative radiation exposure was estimated by using the sensitivity value obtained in the processing of each computed radiograph. Five radiologists assessed the mottle present in the computed radiographs and screen-film images. RESULTS: For computed radiographs, the perceived level of mottle was inversely related to radiation exposure. For the same radiation exposure, the perceived mottle on computed radiographs was significantly higher than that on screen-film images (P < .001 for small cassettes; P < .01 for large cassettes). CONCLUSION: Pediatric computed radiography of the chest requires approximately twice the exposure of a 600-speed screen-film system to attain the same level of mottle.

Child↗
PubMed1996

Pulsatile perfusion system for ex vivo investigation of biochemical pathways in intact vascular tissue.

We have constructed and performed initial validation of an innovative perfusion system that allows exposure of intact segments of vascular tissue to realistic physiological and hemodynamic environments ex vivo. Computer-controlled opening and closing of an in-line gate valve allows generation of arterial pressure waveforms. The control algorithm predicted resultant pressure waveforms with a high degree of accuracy (Pearson correlation coefficient > 0.97). To document vascular homeostasis ex vivo, vasomotor bioassays and morphological studies were performed. The bioassays consisted of injecting epinephrine (2 x 10(-3) mg/ml) into the perfusion system followed by acetylcholine (100 microM) while concurrently measuring vessel diameter with a laser micrometer, significant vasomotion was measured for canine carotid arteries (n = 4) bioassayed after 1, 24, and 48 h of perfusion (P < 0.03). Additionally, human saphenous vein segments were perfused for 24 h (n = 4) and viewed with laser confocal scanning microscopy and transmission electron microscopy; photomicrographs show typical vascular morphology. We conclude that the vascular perfusion system described herein is well suited for investigating the response of intact vascular tissue to hemodynamic variables.

Acetylcholine↗
PubMed1996

The biochemical pathway mediating the proliferative response of bone cells to a mechanical stimulus.

Calvarial bone cells of rats were subjected to either a cyclic biaxial strain of 0.17 per cent (1700 microstrain) or a hydrostatic pressure of 2.5, five, or ten pounds per square inch (17.2, 34.5, or sixty-nine kilopascals). The frequency was held constant at one hertz for both types of mechanical stimulation. When cultured bone cells that had been subjected to a cyclic biaxial strain for two hours were harvested twenty-two hours later, it was found that the level of prostaglandin E2 had increased significantly (p < 0.01) as had cellular proliferation (p < 0.01), as indicated by the incorporation of [3H]-thymidine. The addition to the medium of indomethacin, an inhibitor of prostaglandin synthesis, at a ten-micromolar concentration significantly inhibited (p < 0.01) the increase in prostaglandin E2 synthesis but had no effect on the strain-induced increase in cellular proliferation, as indicated by the incorporation of [3H]-thymidine. Twenty-four hours after exposure to the same cyclic biaxial strain for thirty seconds, other cultured bone cells showed a significant increase in the level of cytoskeletal calmodulin (p < 0.05) and in the DNA content (p < 0.05). N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7), a calmodulin antagonist, was added to the medium at a one-micromolar concentration, which had been shown to have no effect on the increase in the DNA content of control cells; W-7 completely blocked the increase in the level of cytoskeletal calmodulin and in the DNA content in the cells that were subjected to a cyclic biaxial strain. The bone cells subjected to a hydrostatic pressure showed a dose-dependent increase in the concentration of cytosolic Ca2+, as measured with Fura 2-AM, a fluorescent indicator of intracellular calcium. With a pressure of ten pounds per square inch (sixty-nine kilopascals), the increase in the concentration of cytosolic Ca2+ was nearly eight times greater than that at 2.5 pounds per square inch (17.2 kilopascals) (126 +/- 15.2 compared with 16 +/- 8.0 nanomolar, mean and standard deviation). The addition to the medium of neomycin, an inhibitor of the inositol phosphate cascade, at a ten-millimolar concentration completely blocked the increase in the concentration of cytosolic Ca2+ in these cells; this concentration of neomycin had been shown to have no effect on proliferation in control bone cells. There was also a dose-dependent relationship between the duration of the stimulus and the cellular proliferation. Remarkably, one cycle of pressure at ten pounds per square inch (sixty-nine kilopascals) and a frequency of approximately one hertz produced a 57 per cent increase in the incorporation of [3H]-thymidine at twenty-four hours (p < 0.001). From these findings, we hypothesized that the inositol phosphate cascade-cytosolic Ca(2+)-cytoskeletal calmodulin system plays a dominant role in the signal transduction of a mechanical stimulus into increased proliferation of bone cells, at least under the conditions reported here.

Animals↗
PubMed1996

Predicting long-term performance of irradiation polymers.

Material degradation occurs during and after irradiation sterilization. The degree of post-degradation can be accelerated by altering the temperature, environment, and irradiation dose. This article discusses methods to accelerate post-degradation and how this can be used as a predictive technique for evaluating new or improved polymer formulations.

Polymers↗
PubMed1996

The effect of intravesical mitomycin C on recurrence of newly diagnosed superficial bladder cancer: a further report with 7 years of follow up.

PURPOSE: We determined the role, if any, of 1 and 5 instillations of intravesical mitomycin C in the treatment of newly diagnosed superficial bladder cancer. MATERIALS AND METHODS: A multicenter randomized clinical trial was done involving 502 patients with newly diagnosed superficial bladder cancer. After complete transurethral resection patients with newly diagnosed superficial bladder cancer. After complete resection patients were randomized into 1 of 3 treatment arms: no further treatment, 1 instillation of mitomycin C at resection and 1 instillation at resection and at 3-month intervals for 1 year (total 5 instillations). The dose of mitomycin C used was 40 mg./40 ml. water. End points were interval to first superficial recurrence, recurrence rate (defined as the number of positive cystoscopies per year) and progression-free interval rate (progression defined as the development of muscle invasive or metastatic disease, or death from bladder cancer). RESULTS: After median followup of 7 years 1 and 5 instillations of mitomycin C resulted in decreased recurrence rates and increased recurrence-free interval. The benefit of mitomycin C was observed in patients at low, medium and high risk for subsequent recurrence. There was suggestive but not conclusive evidence that 5 instillations of mitomycin C offered a slight advantage over 1 instillation. CONCLUSIONS: Our analysis confirms the positive benefit of mitomycin C to decrease the number of subsequent recurrences and increase the recurrence-free interval.

Administration, Intravesical↗
PubMed1996

Neonatal gastrointestinal imaging.

As an aid to practicing neonatologists, the many gastrointestinal anomalies and diseases found in neonates are discussed with regard to choosing the most efficient and appropriate imaging modalities in each. The discussion is organized under anatomical headings: esophagus, stomach, small bowel, colon, liver, and miscellaneous. Nine representative images are included as illustrations. There is a brief discussion of umbilical arterial and venous catheters.

Catheterization, Peripheral↗
PubMed1995

Morphogenetic reorganization of the brain during embryogenesis in the grasshopper.

We have studied the morphogenetic reorganization that occurs in the grasshopper brain during embryogenesis. We find that morphogenetic movements occur at three organizational levels during brain development. First, the entire developing brain changes its orientation with respect to the segmental chain of ventral ganglia. A 90 degrees shift in the attitude of the brain neuraxis occurs during embryogenesis due to a gradual upward movement of the cerebral structures in the head. Second, the clusters of proliferating neuroblasts and progeny that generate the neuroarchitecture of the mature brain move relative to one another and to nonneural structures such as the stomodeum. This is especially pronounced for the pars intercerebralis and for the tritocerebrum, as shown by annulin and engrailed immunoreactivity. Third, individual neuroblasts within a given proliferative cluster undergo positional reorganization during embryogenesis. Identified neuroblasts of the tritocerebrum and the pars intercerebralis are displaced within the brain. We conclude that the transformation of the simple sheet-like structure of the early embryonic brain into the highly differentiated structure of the mature brain involves a series of morphogenetic movements that occur in virtually all parts of the brain.

Animals↗
PubMed1995

Quantitative analysis of trabecular microstructure by 400 MHz nuclear magnetic resonance imaging.

A new approach for the quantitative analysis of trabecular microstructure, based on high-field proton nuclear magnetic resonance (NMR) imaging, is presented. NMR is ideal because it provides high contrast between the marrow proton signal and the bone, which appears with background intensity. Images from 1 cm3 defatted specimens of trabecular bone, suspended in water doped with 1 mM Gd(DTPA) to shorten T1 to about 300 ms, can be obtained at a resolution on the order of 30-50 microns and slice thickness of 150 microns, in 10 minutes at 400 MHz proton frequency. Digital image processing algorithms were designed and evaluated for the measurement of bone area fraction, perimeter length, mean trabecular thickness, and separation. Bone area fraction derived from the NMR images was found to be in excellent agreement with bone volume fraction measured independently (slope = 0.96, r2 = 0.924, p < 0.0001). Errors in the mean trabecular thickness and separation were < 6%. The effects of finite imaging slice thickness and signal-to-noise ratio (SNR) were also evaluated. The data suggest a resolution of 50 x 50 x 200 microns 3 and an SNR on the order of 10 to provide safe margins for precise and accurate structural analysis by means of the algorithms presented in this paper. The method allows simultaneous measurement at multiple locations within the specimen volume without the need for physical sectioning.

Algorithms↗
PubMed1995

Three-dimensional nuclear magnetic resonance microimaging of trabecular bone.

The conventional approach to measuring structural parameters in trabecular bone rests on stereology from optical images, derived from sections of embedded bone. In order to provide data that are statistically representative of a sufficiently large volume, multiple sections need to be analyzed in each of the three orthogonal planes. In this work, an alternative technique is presented which is based on three-dimensional (3D) volumetric proton nuclear magnetic resonance (NMR) microimaging. The method presented provides from 9 x 9 x 4 mm3 volumes of defatted bone specimens in 15-20 minutes scan time at isotropic resolution corresponding to (78 microm)3 voxel size. Surface-rendered images of bovine and human trabecular bone are shown and an algorithm was developed and implemented for determining the orientation and magnitude of the principle axes of the mean intercept length tensor.

Adult↗
PubMed1995

The CAT-Tox (L) assay: a sensitive and specific measure of stress-induced transcription in transformed human liver cells.

Identifying and measuring the molecular mechanisms of toxicity is an important goal in hazard assessment. We have developed an assay in transformed human liver cells to simultaneously measure the transcriptional responses of 14 stress promoter- or response element-chloramphenicol acetyl transferase (CAT) fusion constructs that are stably integrated into the HepG2 cell line. This assay can measure a wide spectrum of stresses, both toxic and nontoxic, such as protein and protein biosynthesis perturbations, DNA damage, heavy metals, and planar aromatic hydrocarbons. We found that each promoter or response element can be induced by one or more of four chemicals that were tested in the assay. These results have been interpreted in light of the current models of action for each compound. The responses of this assay system can distinguish among compounds that are closely related in their structure and have been shown previously to elicit similar biological activities in simple assay systems. We have designated this technique the CAT-Tox (L)iver assay. It measures a broad range of cellular stresses and toxicants at levels that were comparable to or below those of established methods. The induction profiles generated using the CAT-Tox (L) assay can help to elucidate the molecular mechanisms by which chemicals exert their actions on human cells. These profiles can be indicative of both toxic and nontoxic processes that are occurring in the cell. We propose that this cellular stress assay can serve as a screen for a variety of substances at the molecular level.

Base Sequence↗