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PubMed1992

Establishment and characterization of a human T-cell lymphoblastic lymphoma cell line (HT-1) carrying an inversion of chromosome 14.

A new human lymphoblastic lymphoma cell line was established (designated HT-1) from the pleural fluid lymphoma cells of a patient with lymphoblastic lymphoma of T-cell type. The HT-1 cells expressed CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD57, and terminal deoxynucleotidyl transferase (TdT) but lacked B-cell-associated antigens and myeloid-associated antigens. In addition, HT-1 cells had rearranged T-cell receptor (TCR) beta-chain gene and gamma-chain gene but retained germlines of immunoglobulin (Ig) heavy chain gene. These findings indicate that HT-1 cell line represents a common thymocyte in the T-cell lineage. Cytogenetic studies revealed that HT-1 cells carry an inversion (inv) of the long arm of chromosome 14. This cell line is the second T-cell line carrying inv(14) chromosome and may be useful for the molecular investigation of the cytogenetic break points of inv(14).

Adult↗

PubMed2006

Transducer sensitivity compensation using diagonal preconditioning for time reversal and Tikhonov inverse filtering in acoustic systems.

Filters are commonly used in sound reproduction and communication systems as a means of compensating for the response of the electro-acoustic plant. Two commonly used filter designs in the field of acoustics are the time reversal filter and the Tikhonov inverse filter. In this paper the influence of transducer sensitivities on the performance of these filters is examined. It is shown that the sensitivity of the transducers can negatively affect the performance of the resulting filter. To compensate for the decrease in performance, diagonal preconditioning can be implemented in the system. It is shown that by using diagonal matrices, which minimize the condition number of the system, the loss in performance arising from unbalanced sensitivities is minimized. This paper proposes an algorithm to find such a set of diagonal matrices and results are presented showing the improvements in performance arising from the modified filter design.

Journal Article↗

PubMed2004

Reversal of antigen-dependent signaling by two mutations in antibody/receptor chimera: implication of inverse agonism in cytokine receptor superfamily.

Understanding the receptor activation mechanism is essential for the rational design of pharmacologically active ligand molecules. However, the activation mechanism of most cytokine receptors remains still unclear, and while agonism and antagonism have been described for ligand-mimetic peptides, there has been no report of inverse agonism that has been characterized for G protein-coupled receptors (GPCRs). To explore the activation mechanism of cytokine receptors, here we tried to investigate how agonism and antagonism could be altered by randomizing antibody variable region of an antibody/cytokine receptor chimera recognizing hen egg lysozyme (HEL) as an agonist. Based on our previous finding that the co-expression of V(H)-gp130 and V(L)-erythropoietin receptor (EpoR) chimeras transduced strict and efficient HEL-dependent cell growth signal, a V(H)-gp130 library encoding four randomized CDR2 residues was retrovirally infected to IL-3-dependent Ba/F3 cells already transfected with V(L)-EpoR. The selection without IL-3 resulted in a clonal expansion of the transduced cells, and interestingly some of which showed HEL dose-dependent growth suppression. Our results clearly indicate that agonism and antagonism of the antibody/cytokine receptor chimera can be readily switched by a subtle modification of the ligand binding domain as well as that of GPCRs, also implying the existence of inverse agonism in cytokine receptor superfamily.

Animals↗

PubMed2004

Exact half pulse synthesis via the inverse scattering transform.

In a paper of Nielson et al. it is shown, using the linear approximation, that it might be possible to create a pair of RF-pulses, which, after summation of the unrephased signals achieve a specified transverse magnetization. Such pulses, designed using the linear approximation, show rather poor slice selectivity. Using the inverse scattering transform formalism we give an algorithm to exactly achieve a specified "summed" transverse magnetization profile. Indeed for a constant phase transverse profile, our algorithm produces infinitely many solutions.

Journal Article↗

PubMed2005

Bayesian solutions and performance analysis in bioelectric inverse problems.

In bioelectric inverse problems, one seeks to recover bioelectric sources from remote measurements using a mathematical model that relates the sources to the measurements. Due to attenuation and spatial smoothing in the medium between the sources and the measurements, bioelectric inverse problems are generally ill-posed. Bayesian methodology has received increasing attention recently to combat this ill-posedness, since it offers a general formulation of regularization constraints and additionally provides statistical performance analysis tools. These tools include the estimation error covariance and the marginal probability density of the measurements (known as the "evidence") that allow one to predictively quantify and compare experimental designs. These performance analysis tools have been previously applied in inverse electroencephalography and magnetoencephalography, but only in relatively simple scenarios. The main motivation here was to extend the utility of Bayesian estimation techniques and performance analysis tools in bioelectric inverse problems, with a particular focus on electrocardiography. In a simulation study we first investigated whether Bayesian error covariance, computed without knowledge of the true sources and based on instead statistical assumptions, accurately predicted the actual reconstruction error. Our study showed that error variance was a reasonably reliable qualitative and quantitative predictor of estimation performance even when there was error in the prior model. We also examined whether the evidence statistic accurately predicted relative estimation performance when distinct priors were used. In a simple scenario our results support the hypothesis that the prior model that maximizes the evidence is a good choice for inverse reconstructions.

Algorithms↗

PubMed2006

The percentage of beds designated for medicaid in american nursing homes and nurse staffing ratios.

Previous analyses of the inverse relationship between a nursing home's Medicaid census and its quality of care have been based on samples limited to specific geographic regions, for-profit entities, or only skilled care facilities. The present study uses national-level data from the 1999 National Nursing Home Survey to examine the association between the proportion of beds designated for Medicaid residents and nurse staffing ratios. The results indicate that homes which designate a higher proportion of their beds for Medicaid recipients maintain lower ratios of registered nurses and nurse's aides to residents, even when key facility characteristics are controlled. It was also found that nursing homes with a higher proportion of Medicaid beds offer lower nursing ratios regardless of their profit status or the difference between private pay rates and Medicaid reimbursement rates. Since lower nursing ratios have been previously linked to negative outcomes, these findings suggest that homes which rely more heavily upon Medicaid recipients may be using cost-cutting strategies which have negative implications for quality.

Bed Occupancy↗

PubMed2003

Inverse relation between osteoporosis and spondylosis in postmenopausal women as evaluated by bone mineral density and semiquantitative scoring of spinal degeneration.

STUDY DESIGN: The relation between bone mineral density and severity of spondylosis was evaluated in postmenopausal women. OBJECTIVE: To examine the possible inverse relation between osteoporosis and spondylosis by evaluating the association between bone mineral density and osteophyte formation or intervertebral disc narrowing using a semiquantitative scoring system. SUMMARY OF BACKGROUND DATA: The literature contains studies demonstrating an inverse relation between osteoporosis and spondylosis as well as those documenting insufficient support for such a relation. However, in these studies, only limited-range grading systems (e.g., Grades 1-4) were used to evaluate the severity of spondylosis. METHODS: In this study, 104 postmenopausal women older than 60 years underwent bone mineral density measurement of the lumbar spine (anteroposterior, lateral, and midlateral) and proximal femur (femoral neck, trochanter, and Ward's triangle) using dual-energy x-ray absorptiometry. Raw data representing the semiquantitative osteophyte score and disc score as well as the number of vertebral fractures were obtained using spinal radiograph. Correlations between bone mineral density and the radiographic variable were then analyzed. RESULTS: Significant negative correlations were found between all bone mineral density data and the number of vertebral fractures (-0.524 < or r= r < or = -0.347; P < 0.05). Marginal/moderate positive correlations were observed between the osteophyte score and the bone mineral density data (0.263 < or = r < or = 0.580, P < 0.05), and between the disc score and the bone mineral density data (0.233 < or = r < or = 0.570, P < 0.05).CONCLUSIONS On the basis of the finding that spondylotic changes in postmenopausal women exhibit positive correlations not only with the lumbar bone mineral density, but also with the remote-site bone mineral density, this study supports the view that osteoporosis has an inverse relation with spondylosis.

Aged↗

PubMed2004

Power of test considerations for beef cattle experiments: a review.

The use of power tests in the planning and design of beef cattle experiments provides critical information on sample sizes necessary to detect treatment differences at a predetermined significance (alpha) level. Retrospective power analysis provides additional information about previous experiments that may be helpful in designing subsequent investigations. However, in retrospective power analyses, power is inversely related to observed significance level. Benefits of prospective and retrospective power analyses in beef cattle experiments are similar to those for other species; however, because of differences in the methods and conditions involved, considerations for the use of power test procedures are specific for beef cattle research. Retrospective power analyses were conducted on 78 published experiments and on two unpublished experiments. Experiments were compiled into categories that represented group (or pen) feeding, individual feeding, and metabolism studies. Estimated power in pen feeding experiments using randomized block designs (RBD, n = 30) was less than 0.80 for ADG and feed efficiency (FE), but not different from 0.80 for completely random designs (CRD, n = 4). Furthermore, estimated power was less for ADG than for FE in both design types. For individual feeding experiments using RBD (n = 4), power was not different from 0.80 for either ADG or FE; however, for CRD (n = 18), power was less than 0.80 for both ADG and FE. Power was similar for ADG and FE for both RBD and CRD in individual feeding experiments. In metabolism experiments, estimated power for nitrogen retention was less than 0.80 for Latin square designs (n = 20) but not for CRD (n = 4). Comparisons of power between experimental design types were likely influenced by the number of experiments involved. These results indicate that retrospective power in beef cattle experiments is affected by design type, and response variable measured.

Animal Nutritional Physiological Phenomena↗

PubMed2006

Human growth hormone-related iatrogenic Creutzfeldt-Jakob disease with abnormal imaging.

BACKGROUND: Although more than 160 cases of iatrogenic Creutzfeldt-Jakob disease (iCJD) from human growth hormone (hGH) treatment have been documented, to our knowledge abnormal cerebellar findings on magnetic resonance imaging (MRI) have not been reported. OBJECTIVE: To report a case of hGH-related iCJD with abnormal cerebellar MRI findings on fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted MRI (DWI). DESIGN: Case report. SETTING: Outpatient neurology clinic at a university medical center. PATIENT: A 33-year old man who had subacute gait ataxia and blurred vision. RESULTS: Beginning 19 years prior, this patient had received cadaveric pituitary-derived hGH treatment for at least 5 years. Magnetic resonance imaging revealed FLAIR and DWI abnormalities, particularly in the cerebellum. He died 7 months after disease onset of autopsy-confirmed iCJD. Pathological changes corresponded largely to MRI findings. CONCLUSIONS: To our knowledge, this is the first case of hGH-related iCJD with FLAIR and DWI abnormalities within the cerebellum. As symptoms referable to the cerebellum occur early in iCJD, it suggests that these MRI sequences may allow earlier diagnosis of this form of prion disease.

Adult↗

PubMed1998

Application of chromosome painting to clastogenicity testing in vitro.

To maximise sensitivity, protocols for testing chemicals in chromosomal aberration assays in vitro are designed so that cells are sampled when the peak frequency of aberrations might be expected to occur. They are not designed to measure the frequency of aberrations in cells which survive. Only chromosomal aberrations which are heritable, however, can have any relevance to human health, but the detection of those aberrations most likely to be tolerated (inversions, reciprocal translocations) is notoriously difficult with conventional light microscopy. Current protocol design is justified by arguing that the presence of structural aberrations of any type at early times after treatment indicates a risk that a proportion of aberrations will persist and be maintained in the population. Chromosome painting allows reciprocal exchanges to be relatively easily measured and permits the validity of these assumptions to be tested. To date, the kinetics of induction and dose-response relationships of reciprocal translocations induced by chemicals have been little investigated. We compared the frequency of chromosome-type aberrations in human lymphocytes following treatment with two powerful clastogens, streptonigrin and Trenimon, using conventional staining techniques and chromosome painting. The results show that although reciprocal translocations can be shown to arise and persist in treated populations of human lymphocytes for several days following treatment, their frequency is very low, even at concentrations where large amounts of chromosomal damage are induced, indicating that, at present, the value of using chromosome painting as an adjunct to traditional clastogenicity testing is limited.

Chromosome Aberrations↗

PubMed2000

Design of improved spectral-spatial pulses for routine clinical use.

Spectral-spatial pulses (spsp pulses) selectively excite spins at spatial location z and spectral frequency (due to chemical shift and/or field inhomogeneity) v. In this work we discuss the design of improved spsp pulses for fat signal suppression. Optimal pulses are designed as optimal constant ripple FIR filters using the inverse SLR transform. Spsp pulses with thin slices are obtained by modifying the phases between subpulses, thereby eliminating unwanted magnetization lobes. Robust spsp pulses at off-center slices are obtained with a prescan calibration. These pulses are used either for selective fat saturation or for selective water excitation. It is shown that spsp pulses suppress fat signal better than conventional fat saturation pulses. Using the techniques presented in this article, we replaced all the fat saturation pulses on our systems with spsp pulses and obtained a significant improvement in image quality.

Adipose Tissue↗

PubMed1991

Boundaries in gravitational and magnetic activation of cells for sorting.

Standard deviations in the distribution of radii of cells and particles are considered to arrive at realistic limits in the use of gravitational and magnetic activation of cells for sorting. Using a specific fractionation design, it is shown that the radius of particles (or cells) may be fractionated down to a precision of +/- 0.76%. Although higher precisions could be obtained with other designs, the number of particles available per fraction is inversely proportional to the precision desired. Thus, one would prefer to keep the precision as moderate as permissible by the experiments.

Animals↗

PubMed1989

Computer-controlled discontinuous rotating gel electrophoresis for separation of very large DNA molecules.

The newly designed equipment for alternating field gel electrophoresis which permits the separation of very large DNA molecules and the simultaneous analysis of up to 35 samples is described. The field alternation is effected by intermittently rotating the submerged agarose gel by optitional angles. The time intervals between changes of position are controlled by a computer program driving a simple switching device which was designed to suit any technique using periodic switching or inversion of the electrical field. Because the electrophoresis unit provides an absolutely homogeneous electrical field, no distortion of migration lanes occurs and the resolution is very good. Moreover, by using a switching time interval gradient an almost perfect linear relationship between migration distances and molecule sizes in the range of about 100-1250 kilobase pairs is observed. In two-dimensional separations, different switching time programs for the first and second dimension allow maximum resolution of selected size ranges. Field inversion gel electrophoresis is possible as well. The performance of the method is demonstrated by comparing the chromosome sizes of different yeast strains.

Bacteriophage lambda↗

PubMed1998

A feasibility study of automated inverse treatment planning for cancer of the prostate.

PURPOSE: The development of automated "inverse planning," utilizing intensity-modulated radiation therapy (IMRT) raises the question of whether this new technique can provide a practical and efficient means of dose escalation in conformal treatment of cancer of the prostate. The purpose of this feasibility study was to determine a single set of inverse-planning parameters that can be used for a variety of different prostate patient geometries to automatically generate escalated dose (> or = 81 Gy) IMRT plans that satisfy normal tissue constraints for rectal and bladder walls. METHODS: We studied a subset of the 46 patients who were previously treated at Memorial Sloan Kettering Cancer Center (MSKCC) to a total dose of 81 Gy using a 3D conformal approach. Six patients were selected for our study and replanned using an analytical inverse-planning algorithm (referred to as OPT3D) applied to 8 intensity modulated, co-axial radiation beams. A set of more than a dozen inverse planning parameters were adjusted by trial and error until the resulting dose distributions satisfied the critical organ dose-volume constraints imposed by our study rules (D30 < or = 75.6 Gy and D10 < or = 80 Gy for the rectal wall; D15 < or = 80 Gy for the bladder wall) for the sample of patients selected. The OPT3D-generated plans were compared to hand-generated BEV plans using cumulative DVH analysis. RESULTS: A single set of inverse-planning parameters was found that was able to automatically generate IMRT plans meeting all critical organ dose-volume constraints for all but one of the patients in our study. [The exception failed to meet bladder dose constraints for both IMRT and BEV methods, due to extensive overlap between the planning target volume (PTV) and bladder contours]. Based upon analysis of the cumulative dose-volume histogram (DVH) for the prostate PTV, the D95 (DX is defined such that x% of the volume receives a dose > or = DX), averaged over all patients, was approximately 81 Gy. The average D90 and mean dose values were 85 Gy and 93 Gy, respectively. Although a similar D95 was achieved using the BEV-generated plans, the D90 and mean dose values were substantially higher for the inverse planning (OPT3D) method. CONCLUSION: This limited "paper study" shows IMRT with inverse planning to be a promising technique for the treatment of prostate cancer to high doses. We determined a small set of inverse-planning parameter values that was able to automatically design intensity-modulated radiotherapy (IMRT) plans for a subset of 6 patients previously treated at MSKCC to 81 Gy using BEV planning techniques. With one minor exception, the resulting plans succeeded in meeting predetermined dose-volume constraints while at the same time allowing an increase in the mean dose and D90 to the prostate PTV. These 8 field plans also resulted in reduced dosage to the femoral heads. This automated technique is efficient in terms of planning effort and, with proper software for computer-controlled MLC, may be appropriate for clinical use. The clinical feasibility of this approach for a larger group of patients is currently under study.

Feasibility Studies↗

PubMed1999

Selection and sequencing of interchromosomal rearrangements from gamma-irradiated normal human fibroblasts.

PURPOSE: To determine the sequences that flank sites of interchromosomal DNA rearrangements and to determine the relative frequency of inter- and intrachromosomal rearrangements induced by 30 Gy gamma-irradiation in a region 5' from exon I of the c-myc gene in normal human fibroblasts (IMR-90). MATERIALS AND METHODS: A modification of an inverse polymerase chain reaction (PCR) procedure, developed previously to detect rearrangements, was used. Inverse PCR products were re-amplified using primers designed to determine whether the product was a result of an inter- or intrachromosomal rearrangement. Possible interchromosomal rearrangements were then sequenced. RESULTS AND CONCLUSIONS: Four of 12 different products analyzed were potentially derived from interchromosomal rearrangements, while the remainder derived from intrachromosomal rearrangements. For three of the potential interchromosomal rearrangements, the sequence recombining with c-myc was unidentified, while in the other case the sequence was homologous to an L1 element. The frequencies of inter- and intrachromosomal rearrangements induced by 30 Gy gamma-irradiation in a 2 kbp region flanking the c-myc gene of IMR-90 cells were calculated to be at least 1.6x10(-4) and 3.3x10(-4) respectively. No clear association between sequence context and sites of radiation-induced rearrangement was found; however, two of the four sequenced rearrangements involved breakpoints in the 5'-flanking region of c-myc that occurred immediately after the sequence AAAGG.

Base Sequence↗

PubMed1999

A spline-regularized minimal residual algorithm for iterative attenuation correction in SPECT.

In SPECT, regularization is necessary to avoid divergence of the iterative algorithms used for non uniform attenuation compensation. In this paper, we propose a spline-based regularization method for the minimal residual algorithm. First, the acquisition noise is filtered using a statistical model involving spline smoothing so that the filtered projections belong to a Sobolev space with specific continuity and derivability properties. Then, during the iterative reconstruction procedure, the continuity of the inverse Radon transform between Sobolev spaces is used to design a spline-regularized filtered backprojection method, by which the known regularity properties of the projections determine those of the corresponding reconstructed slices. This ensures that the activity distributions estimated at each iteration present regularity properties, which avoids computational noise amplification, thus stabilizing the iterative process. Analytical and Monte Carlo simulations are used to show that the proposed spline-regularized minimal residual algorithm converges to a satisfactory stable solution in terms of restored activity and homogeneity, using at most 25 iterations, whereas the non regularized version of the algorithm diverges. Choosing the number of iterations is therefore no longer a critical issue for this reconstruction procedure.

Algorithms↗

PubMed1994

Characteristics of magnetic resonance sequences used for imaging silicone gel, saline, and gel-saline implants at low field strengths.

RATIONALE AND OBJECTIVES: Low-field magnetic resonance imaging (MRI) evaluation of breast implants is described, with emphasis on the capabilities provided by different imaging sequences. METHODS: Open architecture MR images using a .064-T permanent magnet and three-dimensional Fourier transform and inversion recovery sequences were obtained. A breast coil was designed and built for this project. Symptomatic and asymptomatic patients with silicone, saline-silicone and saline implants, and phantoms were part of this study. Phase images were used to differentiate protons in silicone, water, and fat. RESULTS AND CONCLUSIONS: Low-field MRI permitted differentiation of silicone, water, and fat. Implant anatomy and surrounding pathology could be imaged and identified.

Adult↗

PubMed2004

Inflammatory response of human tendon fibroblasts to cyclic mechanical stretching.

BACKGROUND: The cellular and molecular mechanisms for the development of tendinopathy are not clear, but inflammatory mediators produced by tendon fibroblasts in response to repetitive mechanical loading may be an important factor. HYPOTHESES: (1) Cyclic stretching of tendon fibroblasts affects the production of leukotriene B(4) and the expression of 5-lipoxygenase; and (2) the production level of leukotriene B(4) is inversely related to that of prostaglandin E(2). STUDY DESIGN: Controlled laboratory study. METHODS: Human patellar tendon fibroblasts were uniaxially stretched in the presence of indomethacin (25 micro M) or MK-886 (10 micro M). After stretching for 4 hours, followed by 4 hours rest, levels of prostaglandin E(2), leukotriene B(4), and expression of 5-lipoxygenase were measured. RESULTS: Stretched tendon fibroblasts increased the levels of leukotriene B(4) but did not appreciably change the expression of 5-lipoxygenase. Indomethacin decreased the cellular production of prostaglandin E(2) but caused increased leukotriene B(4) levels. MK-886 caused decreased production of leukotriene B(4) but increased production of prostaglandin E(2). CONCLUSIONS: Cyclic stretching of human tendon fibroblasts increases the production of prostaglandin E(2) and leukotriene B(4). Blocking prostaglandin E(2) production leads to increased leukotriene B(4) levels and vice versa. CLINICAL RELEVANCE: The use of nonsteroidal anti-inflammatory drugs for the treatment of tendon inflammation might increase the levels of leukotriene B(4) within the tendon, potentially contributing to the development of tendinopathy.

Adult↗