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Biomedical subjects

G Holland

Publications and source records attributed to G Holland.

At least 19 recordsLinked to original sources
PubMed2005

Experimental benchmark for an improved simulation of absolute soft-x-ray emission from polystyrene targets irradiated with the Nike laser.

Absolutely calibrated, time-resolved spectral intensity measurements of soft-x-ray emission (hnu approximately 0.1-1.0 keV) from laser-irradiated polystyrene targets are compared to radiation-hydrodynamic simulations that include our new postprocessor, Virtual Spectro. This new capability allows a unified, detailed treatment of atomic physics and radiative transfer in nonlocal thermodynamic equilibrium conditions for simple spectra from low-Z materials as well as complex spectra from high-Z materials. The excellent agreement (within a factor of approximately 1.5) demonstrates the powerful predictive capability of the codes for the complex conditions in the ablating plasma. A comparison to data with high spectral resolution (E/deltaE approximately 1000) emphasizes the importance of including radiation coupling in the quantitative simulation of emission spectra.

Journal Article↗
PubMed2002

Extracorporeal liver support: porcine or human cell based systems?

Initial results of the clinical use of primary porcine liver cells for extracorporeal liver support are being reviewed as the cell source is controversial. According to Eurotransplant data 20-25% of explanted donor livers are not transplanted, due to factors such as steatosis or cirrhosis. This number corresponds to the number of patients with acute liver failure who require bridging therapy to transplantation. Primary human liver cells from transplant discards can be isolated, purified and maintained in bioreactors and provide an alternative for cell-based extracorporeal liver support therapy. A four-compartment bioreactor enables recovery from preservation and isolation injury in a three-dimensional network of interwoven capillary membranes with integrated oxygenation, rendering the liver cells from these discarded donor organs viable for clinical utilization. Patient contact with additional animal-derived biomatrix and fetal calf serum can be avoided. The initiation of an in vitro cultivation phase allows cell stabilization, quality control, and immediate availability of a characterized system without cryopreservation. The hypothesis of this paper is that with appropriate logistics and four-compartment bioreactor technology, cells from human liver transplant discards can serve the demand for cell-based therapy, including extracorporeal liver support.

Animals↗
PubMed2001

Validation of the functional fitness age (FFA) index in older Japanese women.

Functional fitness age (FFA), which we previously described, is a measure of functional age that reflects a person's overall physical ability to complete daily tasks such as preparing meals and performing various household chores. The purpose of this study was to validate FFA in two elderly populations: 1) older subjects from different communities, and 2) older subjects participating in an exercise intervention program. FFA was calculated from 4 performance tests: performing arm curls; moving beans with chopsticks; demonstrating functional reach; and sitting and walking around two cones. The first study group was selected from 4 different communities (N=127), and was subdivided into a less active group (N=87) and an active group (N=40). The results of the 4 tests for the less active group were not significantly different from those for the original validation group used in developing the FFA equation. The FFA of the less active group (71.1+/-7.7 yrs) was not different from their chronological age (70.4+/-6.6 yrs). In the active group, except for the arm curls, test scores were significantly higher than those of the original validation group. The FFA of the active group (66.2+/-5.1 yrs) was significantly younger than their chronological age (70.9+/-4.2 yrs). Another group of 14 older women (79.5+/-3.9 yrs) was recruited for pre- and post-training testing. After the 3-month exercise program, they showed significant improvements in sitting and walking around two cones and functional reach; their FFA decreased significantly from 81.5+/-5.0 yrs to 78.3+/-4.5 yrs. The control group selected from the same community (N=16, 79.8+/-5.3 yrs) showed no significant changes in the 4 performance tests, and their FFA remained unchanged. These results indicate that our FFA is highly cross-validated for different Japanese communities, and is sensitive to changes associated with participation in an exercise intervention program.

Activities of Daily Living↗
PubMed2000

A kinesin-related protein, KRP(180), positions prometaphase spindle poles during early sea urchin embryonic cell division.

We have investigated the intracellular roles of an Xklp2-related kinesin motor, KRP(180), in positioning spindle poles during early sea urchin embryonic cell division using quantitative, real-time analysis. Immunolocalization reveals that KRP(180) concentrates on microtubules in the central spindle, but is absent from centrosomes. Microinjection of inhibitory antibodies and dominant negative constructs suggest that KRP(180) is not required for the initial separation of spindle poles, but instead functions to transiently position spindle poles specifically during prometaphase.

Amino Acid Sequence↗
PubMed2000

Kinetic Comparison of Trifluoroacetic Acid Cleavage Reactions of Resin-Bound Carbamates, Ureas, Secondary Amides, and Sulfonamides from Benzyl-, Benzhydryl-, and Indole-Based Linkers.

The kinetics of cleavage reactions of 16 resin-bound carbamates, ureas, secondary amides, and sulfonamides from four different acid labile linkers including benzyl, benzhydryl, and indole linkers has been investigated. The optimized cleavage conditions are generally milder than those commonly used and reported (e.g., 0.5% TFA as opposed to 5%). Among various linkers studied in this work, the indole linker has been found to be the most acid labile followed by the Rink linker. The rate of cleavage of compounds linked to the resin via various functional groups can be summarized as follows: sulfonamide >carbamate approximately urea > amide. This study shows that cleavages of 16 compounds from four different acid labile linkers have been optimized to much milder conditions in terms of TFA concentration and the reaction time. It also demonstrates that single bead FTIR is an effective tool for optimizing cleavage conditions.

Journal Article↗
PubMed2000

Functional coordination of three mitotic motors in Drosophila embryos.

It is well established that multiple microtubule-based motors contribute to the formation and function of the mitotic spindle, but how the activities of these motors interrelate remains unclear. Here we visualize spindle formation in living Drosophila embryos to show that spindle pole movements are directed by a temporally coordinated balance of forces generated by three mitotic motors, cytoplasmic dynein, KLP61F, and Ncd. Specifically, our findings suggest that dynein acts to move the poles apart throughout mitosis and that this activity is augmented by KLP61F after the fenestration of the nuclear envelope, a process analogous to nuclear envelope breakdown, which occurs at the onset of prometaphase. Conversely, we find that Ncd generates forces that pull the poles together between interphase and metaphase, antagonizing the activity of both dynein and KLP61F and serving as a brake for spindle assembly. During anaphase, however, Ncd appears to have no effect on spindle pole movements, suggesting that its activity is down-regulated at this time, allowing dynein and KLP61F to drive spindle elongation during anaphase B.

Anaphase↗
PubMed2000

[Liver cell culture in bioreactors for in vitro drug studies as an alternative to animal testing].

An important consideration for the utilisation of in vitro culture models for studies on drug metabolism as an alternative to animal testing is the maintenance of a defined degree of cell differentiation. Thus, in vitro conditions reflecting as near as possible the in vivo situation of the cells within the whole organ are required. A bioreactor was developed for the cultivation of liver cells which allows the reorganisation of hepatocytes and non-parenchymal cells of the liver in coculture to form three-dimensional, tissue-like structures including extracellular matrix components produced by the cells. In this study, the vitality and metabolic activity of isolated rat hepatocytes was investigated over a two week culture period in bioreactors. The results show that after a reorganisation phase, the cells preserve specific functions, such as protein and urea synthesis capacity and specific cytochrome P450 activities during the culture period, with maximal values during the first week. Possible applications of the model in pharmaceutical industry are studies on metabolite patterns, enzyme induction, drug-drug-interactions, first pass effects and long-term toxicity of drugs.

Animal Testing Alternatives↗
PubMed1999

Residual delay maps unveil global patterns of atmospheric nonlinearity and produce improved local forecasts.

We use residual-delay maps of observational field data for barometric pressure to demonstrate the structure of latitudinal gradients in nonlinearity in the atmosphere. Nonlinearity is weak and largely lacking in tropical and subtropical sites and increases rapidly into the temperate regions where the time series also appear to be much noisier. The degree of nonlinearity closely follows the meridional variation of midlatitude storm track frequency. We extract the specific functional form of this nonlinearity, a V shape in the lagged residuals that appears to be a basic feature of midlatitude synoptic weather systems associated with frontal passages. We present evidence that this form arises from the relative time scales of high-pressure versus low-pressure events. Finally, we show that this nonlinear feature is weaker in a well regarded numerical forecast model (European Centre for Medium-Range Forecasts) because small-scale temporal and spatial variation is smoothed out in the grided inputs. This is significant, in that it allows us to demonstrate how application of statistical corrections based on the residual-delay map may provide marked increases in local forecast accuracy, especially for severe weather systems.

Atmosphere↗
PubMed1996

Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses.

We have characterized the progressive stages of chronic intestinal inflammation that develops spontaneously in specific pathogen-free (SPF) mice with a targeted disruption in the IL-10 gene (IL-10-/-). Our longitudinal studies showed that inflammatory changes first appear in the cecum, ascending and transverse colon of 3-wk-old mutants. As the disease progressed, lesions appeared in the remainder of the colon and in the rectum. Some aged IL-10-/- mice also developed inflammation in the small intestine. Prolonged disease with transmural lesions and a high incidence of colorectal adenocarcinomas (60%) was observed in 6-mo-old mutants. Mechanistic studies have associated uncontrolled cytokine production by activated macrophages and CD4+ Th1-like T cells with the enterocolitis exhibited by IL-10-/- mice. A major role for a pathogenic Th1 response was further suggested by showing that anti-IFNgamma antibody (Ab) treatment significantly attenuated intestinal inflammation in young IL-10-/- mice. When weanlings were treated with IL-10, they failed to develop any signs of intestinal inflammation. Interestingly, IL-10 treatment of adults was not curative but did ameliorate disease progression. Our studies have also shown that inheritable factors strongly influence the disease susceptibility of IL-10-/- mice. In 3-mo-old mutants, intestinal lesions were most severe in IL-10-/- 129/SvEv and IL-10-/- BALB/c strains, of intermediate severity in the IL-10-/- 129 x C57BL/6J outbreds, and least severe in the IL-10-/- C57BL/6J strain.

Aging↗
PubMed1996

Magnetic resonance venography versus contrast venography to diagnose thrombosis after joint surgery.

Magnetic resonance venography is a recently developed, noninvasive means of visualizing the proximal veins of the lower extremity and pelvis. Magnetic resonance venography is compared with standard contrast venography in the diagnosis of proximal deep vein thrombosis after total joint arthroplasty. Two hundred seven extremities were evaluated in a blinded study 5 to 7 days after surgery. Standard contrast venography identified 11 proximal deep vein thromboses. Initial interpretations of the magnetic resonance venographies by staff radiologists identified 5 of the proximal vein thromboses (sensitivity 45%). Two patients with negative standard contrast venographies were identified as positive (specificity 99%). A retrospective review of all magnetic resonance venographies by a dedicated magnetic resonance angiographer identified 10 of 11 deep vein thromboses seen on standard contrast venography (sensitivity 91%). Both false negatives were identified as positives. Standard contrast venography remains the gold standard for identifying proximal vein thromboses. Emerging magnetic resonance imaging techniques have created a potential alternative modality by which to identify deep vein thrombosis. The present study suggests that standard contrast venography continues to be the most accurate modality currently available. Although magnetic resonance venography seems to be accurate, its interpretation requires experience. As costs diminish and experience increases, magnetic resonance venography will have increased importance in the clinical recognition of deep vein thrombosis.

Adult↗
PubMed1995

Cofactors are essential for stem cell factor-dependent growth and maturation of mast cell progenitors: comparative effects of interleukin-3 (IL-3), IL-4, IL-10, and fibroblasts.

Stem cell factor (SCF) possesses many mast cell-stimulating activities, including the ability to support the growth of mucosal-like mast cells (MMCs) and connective tissue mast cells (CTMCs). However, this study shows that, in the absence of accessory cells, SCF does not stimulate the clonal growth of primitive mast cell progenitors. Nevertheless, SCF exhibited potent growth-promoting effects when combined with the cytokines interleukin-3 (IL-3), interleukin-4 (IL-4), and interleukin-10 (IL-10). Our comparative studies have shown that optimal mast cell colony formation occurs when both IL-4 and IL-10 are combined with SCF. However, in the presence of SCF, these two cofactors appear to mediate different effects. IL-4 was more efficient than IL-10 in costimulating the initiation of SCF-dependent colony formation by mast cell progenitors and in sustaining the proliferation of newly generated progeny. On the other hand, IL-4 was less efficient than IL-10 in supporting mast cell differentiation, as evidenced by morphology, cell enlargement, and granule production. Although the actions of IL-4 and IL-10 were not equivalent, additional experiments indicated that their ability to serve as early- and late-acting factors, respectively, were complimentary. We have also found that the mast cells generated in colonies stimulated by IL-4, IL-10, and SCF produced high levels of histamine (6-8 pg per cell). None of the mast cells generated in our cultures synthesized heparin. A phenotypic change from safranin-negative to safranin-positive cells associated with heparin-producing CTMCs was accomplished after coculture of the mast cells with fibroblast cell lines derived from normal mice or from SI/SId mice plus soluble factors. Collectively, our observations demonstrate that SCF acts as a competence factor for mast cell progenitor growth. In addition, the ability of SCF to support certain stages of mast cell differentiation is profoundly influenced by interactions with specific cofactors.

Animals↗
PubMed1994

Combination of ganciclovir and granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients. The ACTG 073 Team.

The efficacy and safety of a combination of ganciclovir plus GM-CSF was evaluated in AIDS patients with cytomegalovirus retinitis. In phase A, patients were randomized to receive ganciclovir, 5 mg/kg every 12 h for 14 days followed by 5 mg/kg daily, with (n = 24) or without (n = 29) GM-CSF (1-8 micrograms/kg daily subcutaneously) to maintain absolute neutrophil counts between 2500 and 5000 cells/microliters. In phase B, after 16 weeks zidovudine was added to the regimen of 16 patients receiving ganciclovir plus GM-CSF and 20 receiving ganciclovir alone. At this stage, GM-CSF was added to the treatment protocol of any patient receiving ganciclovir plus zidovudine who became neutropenic. In phase A, patients in the ganciclovir plus GM-CSF group had significantly higher neutrophil counts than ganciclovir-alone patients (p = 0.0001). Overall, 12.5% of patients treated with GM-CSF developed neutropenia (absolute neutrophil counts < 500/microliters phase A and < 750/microliters phase B) compared with 45% of patients treated without GM-CSF. GM-CSF patients missed 10 of a possible 4705 scheduled doses of ganciclovir compared with 34 missed doses of a possible 6584 in the ganciclovir-alone group (p = 0.011). There was a trend, although not statistically significant, for patients in the GM-CSF group to experience delayed progression of their retinitis.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1993

Recurrent bleeding from anorectal varices: successful treatment with a transjugular intrahepatic portosystemic shunt.

Anorectal varices are portal-systemic collaterals commonly found in patients with portal hypertension. Although these varices rarely bleed, when bleeding does occur it may be massive and life threatening. Anorectal varices may be mistaken for hemorrhoids and there is no agreed upon method for their definitive diagnosis. Additionally, there is no standard therapy for bleeding anorectal varices, and when techniques designed for the control of hemorrhoidal bleeding are employed the results can be disastrous. We report here the first use of a transjugular intrahepatic portosystemic shunt (TIPS) for the permanent control of bleeding anorectal varices. Magnetic resonance imaging/magnetic resonance venography (MRI/V) was used as a non-invasive method for the identification of anorectal varices and to confirm the successful decompression of these varices with TIPS placement. MRI/V and TIPS may provide significant advances in the diagnosis and treatment of rectal variceal bleeding.

Female↗
PubMed1993

Magnetic resonance arteriography of the pelvis and lower extremities.

Reconstructive vascular surgery is the last resort for limb salvage in patients with vascular insufficiency. Planning the sites of arterial bypass grafts depends on an exact knowledge of the angiographic anatomy. Currently, conventional contrast angiography is the primary preoperative study for surgical planning. Recently, magnetic resonance (MR) arteriography has been shown to be an accurate technique for the evaluation of slow arterial flow in the lower extremities. The purpose of this review will be to show how MR arteriography can be used as both an adjunct to and in some cases instead of conventional angiography for the preoperative assessment of lower-extremity vascular reconstruction. The derivation of common artifacts, the many pitfalls of interpretation, and the evaluation of peripheral arterial occlusion and percentage stenosis will be discussed. MR arteriography of the lower extremities is an important advance for the noninvasive evaluation of disease of the peripheral vasculature.

Algorithms↗
PubMed1992

Interleukin 10: an overview.

Since the original description of interleukin-10, a wealth of information concerning its biological properties has been gathered. Studies in vitro have rapidly identified both immunostimulatory and immunosuppressive activities for IL-10. Based on these findings, in vivo studies were initiated in a variety of animal disease models to assess the importance of these activities. This review will summarize the pleiotropic properties of IL-10 and will survey current research regarding the potential of IL-10 to regulate acute and chronic inflammatory reactions.

Animals↗
PubMed1992

Magnetic resonance angiography of the pelvis and lower extremities. Works in progress.

Two-dimensional time-of-flight (TOF) magnetic resonance angiography (MRA) of the lower extremities has recently been rediscovered as a technique that can be used to find small vessels in the foot and leg for surgical revascularization in patients with severe peripheral vascular disease. The purpose of this article is to acquaint the reader with some of the common problems that may be encountered in this imaging technique and to show their derivations and solutions were applicable. In addition, the authors show receiver operator curve analysis of one radiologist's ability to determine the location and patency of arteries using this technique to be outstanding (AZ, 0.9737). This represents a promising new technique for imaging the arterial system in patients with severe peripheral vascular disease.

Blood Vessels↗
PubMed1989

Abrogation of factor-dependence in two IL-3-dependent cell lines can occur by two distinct mechanisms.

We have investigated the mechanisms of abrogation of factor-dependence of lymphoid (FL5.12) and myeloid (FDC-P1) interleukin-3 (IL-3)-dependent cell lines following infection of the cells with retroviruses that encode different oncogenes and immediate selection of IL-3-independent growth. As previously reported by others, Abelson-MuLV (Ab-MuLV) transforms both cell lines to factor-independence, and the transformed cells express the viral oncogene, do not produce IL-3, and are tumorigenic. In contrast, IL-3-independent lymphoid and myeloid cell lines recovered after infection with retroviruses that encode v-src or v-fms oncogenes lacked the v-src or v-fms provirus. Three of seven IL-3-independent transformants were rearranged at the IL-3 locus, produced IL-3-specific mRNA, secreted IL-3 into the culture medium, and grew better in the presence of IL-3. These IL-3-independent transformants produced tumors upon inoculation into nude mice, albeit with longer latent periods than Ab-MuLV transformants. The expression of hematopoietic cell markers was compared in parental and IL-3-independent transformants by immunofluorescence and analysis of mRNA levels. Significant elevation of LFA-1 and MHC class I molecules and loss of expression of IL-2-receptor molecules was detected in most IL-3-independent transformants. These differences in antigen expression indicate that additional phenotypic changes accompany transformation to factor-independence.

Animals↗