Biomedical subjects

A Hubbard

Publications and source records attributed to A Hubbard.

At least 19 recordsLinked to original sources

PubMed1999

Passive electrotonic properties of rat hippocampal CA3 interneurones.

1. The linear membrane responses of CA3 interneurones were determined with the use of whole-cell patch recording methods. The mean input resistance (RN) for all cells in this study was 526 +/- 16 MOmega and the slowest membrane time constant (tau0) was 73 +/- 3 ms. 2. The three-dimensional morphology of 63 biocytin-labelled neurones was used to construct compartmental models. Specific membrane resistivity (Rm) and specific membrane capacitance (Cm) were estimated by fitting the linear membrane response. Acceptable fits were obtained for 24 CA3 interneurones. The mean Rm was 61.9 +/- 34.2 Omega cm2 and the mean Cm was 0.9 +/- 0.3 microF cm-2. Intracellular resistance (Ri) could not be resolved in this study. 3. Examination of voltage attenuation revealed a significantly low synaptic efficiency from most dendritic synaptic input locations to the soma. 4. Simulations of excitatory postsynaptic potentials (EPSPs) were analysed at both the site of synaptic input and at the soma. There was little variability in the depolarization at the soma from synaptic inputs placed at different locations along the dendritic tree. The EPSP amplitude at the site of synaptic input was progressively larger with distance from the soma, consistent with a progressive increase in input impedance. 5. The 'iso-efficiency' of spatially different synaptic inputs arose from two opposing factors: an increase in EPSP amplitude at the synapse with distance from the soma was opposed by a nearly equivalent increase in voltage attenuation. These simulations suggest that, in these particular neurones, the amplitude of EPSPs measured at the soma will not be significantly affected by the location of synaptic inputs.

Analysis of Variance↗

PubMed1999

Caval contribution to flow in the branch pulmonary arteries of Fontan patients with a novel application of magnetic resonance presaturation pulse.

BACKGROUND: A complete understanding of fluid mechanics in Fontan physiology includes knowledge of the caval contributions to right (RPA) and left (LPA) pulmonary arterial blood flow, total systemic venous return, and relative blood flow to each lung. METHODS AND RESULTS: Ten Fontan patients underwent cine MRI. Three cine scans of the pulmonary arteries were performed: (1) no presaturation pulse, (2) a presaturation pulse labeling inferior vena cava (IVC) blood (signal void), and (3) a presaturation pulse labeling superior vena cava (SVC) blood. The relative signal decrease is proportional to the amount of blood originating from the labeled vena cava. This method was validated in a phantom. Whereas 60+/-6% of SVC blood flowed into the RPA, 67+/-12% of IVC blood flowed toward the LPA. Of the blood in the LPA and RPA, 48+/-14% and 31+/-17%, respectively, came from the IVC. IVC blood contributed 40+/-16% to total systemic venous return. The distributions of blood to each lung were nearly equal (RPA/LPA blood=0.94+/-11). CONCLUSIONS: In Fontan patients with total cavopulmonary connection, SVC blood is directed toward the RPA and IVC blood is directed toward the LPA. Although the right lung volume is larger than the left, an equal amount of blood flow went to both lungs. LPA blood is composed of equal amounts of IVC and SVC blood because IVC contribution to total systemic venous return is smaller than that of the SVC. This technique and these findings can help to evaluate design changes of the systemic venous pathway to improve Fontan hemodynamics.

Blood Flow Velocity↗

PubMed1999

Methods for assessing the public health impact of outflows from combined sewer systems.

OBJECTIVES: Approximately 1,100 communities in the United States have combined sewer and stormwater systems whose capacity may be exceeded during moderate or heavy rainfall. Outflows may occur that can deposit water with varying concentrations of the components of sewage onto public areas, where contact with residents or workers is possible, potentially resulting in a range of adverse health effects. This study proposes and applies three analytic methods to evaluate the impact of such outflows on public health. METHODS: The work attendance records of 449 U.S Postal Service letter carriers in Sacramento, CA, were reviewed to determine the frequency of sick leave use (as a surrogate measure of illness) in relationship to rainfall and potential exposure to sewage-contaminated outflows in two distinct groups of letter carriers from October 1, 1992, through April 30, 1993. Rainfall was a surrogate measure of outflows from the combined sewer and stormwater system because no information existed about the extent of exposure of these (or any other) workers. One group of letter carriers delivered mail exclusively within an area served by the combined sewer and stormwater collection system; the second group delivered mail exclusively outside this area where sewage and stormwater collection are separated. The first approach to the assessment of the data was a description of the temporal relationship between rainfall patterns and absentee rates in the two groups of workers. The second approach used logistic regression modelling with varying lags between rainfall and sick leave usage. The third approach used Poisson regression analysis of the entire study period to examine the differential impact of rainfall on the two groups. RESULTS: The descriptive analyses detected no relationship between rainfall and sick leave use. The logistic regression analyses detected evidence (as measured by the interaction coefficient in logistic models) of an increased use of sick leave by the letter carriers within the Combined System area at lag periods of one, four, and five days after rainfall. These estimates were not, however, statistically significant (p > 0.05). The Poisson regression analysis showed no evidence of a differential impact of rainfall on the two groups (incidence rate ratio = 1.19 in both groups for periods of rain versus no rain). CONCLUSIONS: These three methods can be used to investigate the public health impact of combined system outflows. Ideally, however, these approaches would be applied to prospectively collected surveillance data that would rely upon direct measurements of exposure and illness, rather than surrogate variables.

Female↗

PubMed1998

Mechanics of the single left ventricle: a study in ventricular-ventricular interaction II.

BACKGROUND: Left ventricular (LV) effects on right ventricular (RV) function are well known. Less is understood about the effect of the RV on systemic LV mechanics. To determine this interaction, we compared systemic LVs with and without an RV mechanically coupled to them. METHODS AND RESULTS: MR myocardial tagging was used to examine 18 subjects with systemic LVs: 10 with functional single LVs (SLV) and 8 normal subjects (NL). Tracking the systolic motion of the intersecting stripes were used to determine regional twist and radial motion. Finite strain analysis was applied to derive principal strains at the atrioventricular valve (AVV) and apical short-axis levels and in 4 anatomic wall regions. Similar E1 (circumferential shortening) strain and heterogeneity of strain were noted between SLV and NL except in the septal wall. At the septal wall, NL displayed greater absolute strain (AVV=-0.16+/-0.02, apex=-0.17+/-0.02) and less heterogeneity of strain than SLV (AVV= -0.12+/-0.02, apex=-0.13+/-0.02). Similar E2 (wall thickening) strain and heterogeneity of strain were also noted between SLV and NL except again at the septal wall. At the septal wall, SLV displayed greater absolute E2 strain (AVV=0.17+/-0.08, apex=0.19+/-0.09) and less heterogeneity of strain than NL (AVV=0.07+/-0.07, apex=0.05+/-0.05). SLV twisted significantly less counterclockwise than NL in 6 of 8 wall regions and actually twisted clockwise at the AVV lateral wall. Although there was no significant difference between groups in radial wall motion, the septal and inferior walls of SLV demonstrated significantly less radial motion compared with other SLV walls. CONCLUSIONS: A major influence of the RV on systemic LV strain and radial motion occurs in the septal wall, whereas absence of the RV causes marked differences in LV twist. These findings may yield clues to the long-term functioning of the SLV and be useful in determining strategies for RV augmentation of LV function.

Adolescent↗

PubMed1998

Neuropathy target esterase: immunolocalization to neuronal cell bodies and axons.

Determination of the molecular mechanisms involved in organophosphate-induced axonopathy may help to elucidate those involved in normal axonal maintenance and in other neurodegenerative conditions. In this study we aimed to define the cellular distribution of neuropathy target esterase, the primary target protein for neuropathic organophosphates. A synthetic peptide corresponding to the sequence of a proteolytic fragment of neuropathy target esterase purified from chicken brain was used to raise a rabbit antiserum designated R28. The antiserum was shown by immunoprecipitation and western blotting of brain extracts to react with a polypeptide of the expected molecular size (155,000 mol. wt); this reaction was blocked by preincubating the antiserum with the immunizing peptide. Prominent intracellular immunostaining by R28 was seen in neuronal cell bodies and, in some cases, proximal axon segments in frozen sections of chicken brain cortex, optic tectum, cerebellum, spinal cord, and dorsal root ganglia. Cells with glial morphology were not immunostained, neither were normal sciatic nerve or motor end plates. However, 8-12 h following sciatic nerve ligation, immunoreactive material was seen to accumulate both proximal and, to a lesser extent, distal to the ligature, indicating that neuropathy target esterase undergoes fast axonal transport. No gross qualitative or quantitative changes in the above pattern of neuropathy target esterase immunoreactivity were detected in tissue obtained from chickens one or three days following treatment with a neuropathic organophosphate. The presence of neuropathy target esterase in essentially all neurons indicates that the selective vulnerability of long axons to neuropathic organophosphates is dependent on factors additional to the presence of the target protein.

Amino Acid Sequence↗

PubMed1997

Cellular relocalisation of protein kinase C-theta caused by staurosporine and some of its analogues.

The microbial product staurosporine is a protein kinase C (PKC) inhibitor with some phorbol ester-agonistic properties. It is known to cause the translocation of the PKC isoenzymes epsilon and delta from the cellular cytosol to the membrane and nucleus. We tested the hypothesis that it also affects the cellular localisation of the novel PKC isoenzyme theta, and that staurosporine analogues, some of which are currently under clinical evaluation as potential anticancer drugs, have a similar effect. Their ability to alter PKC-theta distribution was studied in human-derived A549 lung carcinoma cells. Western blot analysis and confocal microscopy after indirect immunofluorescence staining showed that staurosporine (100 nM), like the phorbol ester 12-O-tetradecanoylphorhol-13-acetate (25 nM) caused the translocation of PKC-theta from the cytosol to the membrane and the nucleus. The bisindolylmaleimide GF 109203X mimicked staurosporine, but had a weaker effect. Ro 31-8220 and UCN-01 decreased cytosolic PKC-theta only at 1 microM. CGP 41251 had no effect on PKC-theta in either experimental design. The results show that some, but not all, staurosporine analogues share the partial phorbol ester-agonistic PKC-translocatory activity of the parent molecule.

Alkaloids↗

PubMed1997

Repolarization of hepatocytes in culture.

We have evaluated the biochemical, morphological, and functional redevelopment of polarity in freshly isolated hepatocytes cultured using a double layer collagen gel sandwich technique. Western blot analysis showed increased cellular levels of the cell adhesion protein uvomorulin as cultured hepatocytes repolarized. Immunofluorescence studies using antibodies against domain-specific membrane proteins showed polarity as early as 48 hours, although the pattern of the polymeric Immunoglobulin-A receptor (pIgA-R) differed from in vivo liver. Electron microscopy showed developing bile canaliculi at 1 day. However, the functional presence of tight junctions was absent at 1 day, but present at 5 days. We further showed functional polarity to be present at 4 days by documenting the ability of cultured hepatocytes to metabolize and excrete fluorescein diacetate into visible bile canaliculi. We conclude that hepatocytes cultured appropriately develop morphological and functional polarity. Hepatocyte culture is therefore a useful tool for the study of mechanisms responsible for the development of polarized function.

Animals↗

PubMed1997

The nature of flow in the systemic venous pathway measured by magnetic resonance blood tagging in patients having the Fontan operation.

OBJECTIVES: Our objectives were twofold: (1) to determine cardiac and respiratory dependency of systemic venous pathway flow of patients having the Fontan operation with a total cavopulmonary connection and (2) to describe the velocity profile. Systemic venous pathway flow is hypothesized to be mostly respiratory dependent, to be laminar, and to have a smooth velocity profile. METHODS: Twenty-two patients having the Fontan operation (aged 8.6 +/- 4.7 years) underwent magnetic resonance blood tagging (bolus tagging). Systemic venous pathway spin-echo images parallel to the blood flow were used as a localizer. A saturation pulse labeled the blood, and a cine image was acquired at the inferior and superior venae cavae and midportion of the baffle in the systemic venous pathway, triggered to the electrocardiogram and gated to both end-expiration and end-inspiration. Repetition time was 50 msec. RESULTS: Flow in the systemic venous pathway was laminar throughout its course and was found to be phasic to both cardiac and respiratory cycles. Approximately 70% of flow was cardiac dependent, and the rest was respiratory. Highest flow occurred near end-systole and early diastole and in inspiration. Lowest flow occurred in diastasis. Velocity was highest and flow least "pluglike" in the mid-baffle area during cardiac or respiratory imaging (45 +/- 17 and 32 +/- 11 cm/sec, respectively). CONCLUSION: A substantial amount of pulmonary blood flow in patients who have undergone a total cavopulmonary connection type of Fontan operation has a cardiac component. Furthermore, we confirm that this flow is laminar but nonuniform across the systemic venous pathway. Highest flows occurred near end-systole and early diastole, as well as in inspiration, and the lowest flow occurred in diastasis. This information may help in designing the systemic venous pathway and optimizing medical management.

Blood Flow Velocity↗

PubMed1997

Estimation with interval censored data and covariates.

In biostatistical applications interest often focuses on the estimation of the distribution of time T between two consecutive events. If the initial event time is observed and the subsequent event time is only known to be larger or smaller than an observed monitoring time C, then the data conforms to the well understood singly-censored current status model, also known as interval censored data, case I. Additional covariates can be used to allow for dependent censoring and to improve estimation of the marginal distribution of T. Assuming a wrong model for the conditional distribution of T, given the covariates, will lead to an inconsistent estimator of the marginal distribution. On the other hand, the nonparametric maximum likelihood estimator of FT requires splitting up the sample in several subsamples corresponding with a particular value of the covariates, computing the NPMLE for every subsample and then taking an average. With a few continuous covariates the performance of the resulting estimator is typically miserable. In van der Laan, Robins (1996) a locally efficient one-step estimator is proposed for smooth functionals of the distribution of T, assuming nothing about the conditional distribution of T, given the covariates, but assuming a model for censoring, given the covariates. The estimators are asymptotically linear if the censoring mechanism is estimated correctly. The estimator also uses an estimator of the conditional distribution of T, given the covariates. If this estimate is consistent, then the estimator is efficient and if it is inconsistent, then the estimator is still consistent and asymptotically normal. In this paper we show that the estimators can also be used to estimate the distribution function in a locally optimal way. Moreover, we show that the proposed estimator can be used to estimate the distribution based on interval censored data (T is now known to lie between two observed points) in the presence of covariates. The resulting estimator also has a known influence curve so that asymptotic confidence intervals are directly available. In particular, one can apply our proposal to the interval censored data without covariates. In Geskus (1992) the information bound for interval censored data with two uniformly distributed monitoring times at the uniform distribution (for T) has been computed. We show that the relative efficiency of our proposal w.r.t. this optimal bound equals 0.994, which is also reflected in finite sample simulations. Finally, the good practical performance of the estimator is shown in a simulation study.

Analysis of Variance↗

PubMed1996

Leucocyte and endothelial cell adhesion molecule expression in porcine histiocytic leiomyofibrosarcoma.

A histiocytic sarcoma was present at birth in a pig. On the basis of ultra-structure and structural-protein composition (presence of alpha-smooth-muscle actin but not keratin), the sarcoma component was identified as a leiomyofibrosarcoma. Lipid-laden macrophages (histiocytes), which permeated the tumour in an apparently random fashion, were somewhat atypical in that they were negative for some macrophage markers; they gave a reaction, however, for CDw14. Despite its aggressive metastatic capacity, this tumour occurred almost exclusively in the subcutis, dermis and skeletal muscle. The tumour was extensively vascularized with many small capillaries which did not express E-selectin (CD69E), MHC class II or the L-selectin (CD69L) ligand, markers characteristic of inflamed (activated) endothelial cells in pig skin. Significant numbers of the histiocytes were positive for the integrins CD18 and VLA-4 (CD49d), indicating involvement of integrin pathways in the spread or growth, or both, of the leiomyofibrosarcoma. Most of the fibrous sarcoma cells also had extensive reactivity with an antibody to the standard variant form of CD44 (CD44s).

Animals↗

PubMed1996

Pharmacokinetic in vivo comparison using 1-stage and chromogenic substrate assays with two formulations of Hemofil-M.

In a study to demonstrate the safety and pharmacokinetics (half-life and recovery) of two different method M purified AHF (Hemofil-M) concentrates processed in the USA and Spain, two different methods of factor VIII assay (one-stage clotting and chromogenic) have been compared in vivo. The study was a single centre blinded, randomised, crossover study. Twelve patients with severe haemophilia A (VIII:C < 2 u/dl) were divided into two subgroups of six. None had received factor VIII concentrate within 48 h preceding the study. Twenty-four pharmacokinetic studies were performed in the 12 patients. Each subgroup received two different lots of study material (US and Spanish) at a dose of 50 u/kg seven days apart. A second randomisation was nominal potency, high: 1000 u or mid: 500 u per vial. The potency label was a one-stage clotting assay using the mega I standard. A standard pharmacokinetic study was performed over 24 h and each blinded sample was analysed in duplicate by a one-stage clotting (aPTT) and a chromogenic (Chromogenix AB; CS) assay at the Royal Free and NIBSC. Pharmacokinetic modelling was performed. The mean label for Hemofil-M using the chromogenic substrate assay was 79% that using the one stage assay (Mega I standard). The recovery was 17-28% higher measured by chromogenic compared to the clotting assay. Since most clinicians use the clotting assay, potency labelling using the chromogenic assay, will overestimate predicted Hemofil-M recovery by as much as 25%.

Biological Assay↗

PubMed1994

A custom-chip-based functional electrical stimulation system.

The Functional Electrical Stimulation System consists of a host computer and up to 32 chips connected serially. Up to 256 different monophasic constant voltage (0 V-2.5 V), variable frequency (0 Hz-100 Hz in 2 Hz steps; 100 Hz-1700 Hz in 100 Hz steps), and adjustable duration (50 microseconds-200 ms in 50 microseconds steps) pulse trains can be continuously generated.

Computer Systems↗

PubMed1993

Micro-trabeculae, macro-plaques or mini-basement membranes in human term fetal membranes?

Immunocytochemical confocal laser scanning microscopy and ultrastructural analysis, including immunoelectron microscopy, reveals the distribution of structures in human term amniochorion similar in some respects to basement membranes but with unusually restricted dimensions. On the basis of their immunoreactivity, these trabecular structures, found on the fibroblast layer side of the spongy layer of human term amniochorion and adjacent reticular layer, have been shown to contain type IV collagen, laminin, and nidogen. The origin of these components may be from primitive epithelial structures which pumped fluid into the lakes that eventually coalesced to form the extraembryonic coelom separating the extraembryonic somatic mesoderm from the extraembryonic splanchnic mesoderm. Such a theory of their origin might link them with the mysterious 'cellular layer', a single-cell-thick layer of cells which is usually no longer present in fetal membranes at term. The similarity in composition but not in size of these structures to anchoring plaques for type VII collagen is possible support for the view that these structures are integrators of extracellular matrix polymeric proteins. The 'pseudobasement' membrane associated with the trophoblast layer, on investigation, appears to be typical by six criteria. 'Coiled' fibrous structures in the extracellular matrix of the spongy layer may aid adjustments under tension at this shear surface by a detachable 'Velcro' or 'two spring' fastening system. The coils are rich in fibronectin. The suggestion is made that the compact layer is a giant lamina reticularis associated with the amniotic epithelial basement membrane.

Basement Membrane↗

PubMed1993

A traveling-wave amplifier model of the cochlea.

A two-mode model of the cochlea that uses active intermode feedback has been developed that quantitatively accounts for the motion of the basilar membrane in response to single tones and qualitatively accounts for cochlear emission phenomena. In contrast to existing single-mode models, this model amplifies the mechanical traveling wave in spatially localized cochlear regions where an approximate match occurs between the traveling-wave velocities of each of the two traveling-wave lines or modes.

Acoustic Stimulation↗

PubMed1993

Confocal and conventional immunofluorescence and ultrastructural localisation of intracellular strength-giving components of human amniochorion.

Key cytoskeletal polypeptides of human fetal membranes have been localised at subcellular level using confocal and conventional indirect immunofluorescence microscopy. Correlation with electron microscope data has allowed us to examine how cellular compartments of this multilaminar tissue maintain their mechanical integrity until the time of membrane rupture at parturition. Evidence is presented for myofibroblastic characteristics of cells in both the fibroblast and reticular layers which may therefore have tension-generating, position-adjustment and wound-healing roles in the amniochorion. Desmin and vimentin are coexpressed in these cells, but a small localised population of cells in the fibroblast layer contains vimentin alone. An interaction of cytokeratin filaments with nuclei and desmosomes of amniotic epithelium in vivo is demonstrated, indicating that nuclei of cells of ectodermal origin are integrated into a mechanical structure extending throughout the tissue as a whole. Cells of the basal 1 or 2 layers of trophoblast have been shown to have a more extensive and better integrated cytoskeletal organisation than those overlying and forming the boundary with decidua. Structures within the trophoblast, identified previously as degenerate villi, contain cells with intermediate filaments with similar immunofluorescence properties to those of the neighbouring reticular layer and thus may represent papillae that prevent shearing at this interface.

Amnion↗

PubMed1992

Vanadium and copper in clinical solutions of albumin and their potential to damage protein structure.

Solutions of albumin, for injectable use in humans, are shown to contain the transition metals vanadium, copper, and iron. Variation in the concentration of these metal ions among products from six different manufacturers suggests that problems of metal contamination arise through manufacturing processes. Vanadium concentrations correlated with the loss of tryptophan residues in albumin, whereas copper concentrations correlated with loss of thiol groups and tryptophan residues. Incubation of vanadate and cupric salts with the thiol group-containing molecules cysteine and glutathione resulted in reduction of the metal ions to lower oxidation states. Reduced forms of vanadium and copper were able to transfer electrons to molecular oxygen and produce highly reactive and damaging intermediates of oxygen, such as the hydroxyl radical.

Albumins↗

PubMed1991

Normal splenic size in infants and children: sonographic measurements.

The purpose of this study was to establish guidelines for normal splenic size at different ages by using a simple and reproducible sonographic method. Two hundred thirty patients, from neonate to 20-year-old, had sonography because of abdominal and/or pelvic problems unrelated to the spleen. Findings on sonograms of the liver and kidneys were normal in all cases. Splenic size was measured by obtaining a coronal view that included the hilum, while the patient was breathing quietly. The greatest longitudinal distance between the dome of the spleen and the tip (splenic length) was measured and correlated with age, height, and weight. The following guidelines are proposed for the upper limit of normal splenic length based on this simple, easy to use, one-measurement technique: splenic length no greater than 6.0 cm at 3 months, 6.5 cm at 6 months, and 7.0 cm at 12 months, 8.0 cm at 2 years, 9.0 at 4 years, 9.5 cm at 6 years, 10.0 cm at 8 years, 11.0 cm at 10 years, 11.5 cm at 12 years, 12.0 cm at 15 years or older for girls, and 13.0 cm at 15 years or older for boys. Twenty-two patients with known abnormalities of the spleen were randomly selected and their splenic lengths compared with the proposed guidelines; in each case, the length of the spleen exceeded the upper limit of normal for that age. Normal values of a single measurement of the greatest longitudinal diameter of the spleen, from the dome to the tip measured at the hilum in the coronal plane, were obtained in patients from newborn to 20 years old.

Adolescent↗

PubMed1990

Knowledge, attitudes, treatment practices, and health behaviors of nurses regarding blood cholesterol and cardiovascular disease.

Knowledge, attitudes, and practice patterns concerning cholesterol and heart disease were evaluated in a stratified, random sample of 206 registered nurses at a major academic medical center in New York City. Virtually all nurses were convinced of the importance of diet in reducing heart disease risk, and most (78%) agreed that nutrition counseling should be their responsibility. Although only 19% reported that they were currently counseling, many more felt prepared to counsel about diet or drug therapy (43%). Nurses who were likely to counsel were those working in general medicine, those who were certified nurse practitioners, those who knew their own blood cholesterol level, and those with higher knowledge scores. Level of overall knowledge was associated with the practice of counseling, an attitude that counseling should be a nurse's responsibility, and personal health behavior (knew own level), regardless of age or occupational or degree status. Despite their enthusiasm for heart disease prevention through diet modification, many nurses had substantial knowledge gaps, suggesting that nurses are currently not adequately prepared to counsel about diet and/or drug treatment for high blood cholesterol. Educational strategies and considerations in integrating an expanded role for nurses with those of physicians and dietitians are discussed.

Academic Medical Centers↗