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Biomedical subjects

J Fung

Publications and source records attributed to J Fung.

At least 91 records · Page 5Linked to original sources
PubMed1999

Dose-dependent up-regulation of rat pulmonary, renal, and hepatic cytochrome P-450 (CYP) 1A expression by nicotine feeding.

In a previous study in which a single 2.5 mg/kg (15.4 micromol/kg) s. c. dose of nicotine effected a transient, lung-specific induction of cytochrome P-450 (CYP) 1A1 in the rat, a dose-response study and assessment of the lung specificity of the induction was limited by toxicity of the acute parenteral nicotine exposure. In the present study, we examined the dose-CYP1A1/2 induction response relationship and the tissue specificity of the induction by orally administered nicotine, which lacks the toxicity of the parenterally administered drug. Nicotine, administered in a nutritionally balanced liquid diet, at a level of 20 (low), 60 (medium), or 200 (high) mg/kg of diet, induced CYP1A1 in the lung and kidney in a dose-dependent manner and in the liver at the high nicotine dose only, whereas CYP1A2 was induced in the liver dose-dependently and in the kidney at the high nicotine dose only. The high nicotine dose up-regulated mRNA level in the three tissues examined, but with the lung being the most responsive to the up-regulation. Induction of the CYP1A1-preferential activity ethoxyresorufin O-deethylase by the low, medium, and high nicotine diets was 1.9-, 4.9-, and 21.6-fold, respectively, in the lung, 1.4-, 1.7-, and 15.9-fold, respectively, in the kidney, and 1.7-, 2.9-, and 5.1-fold, respectively, in the liver. Similarly, albeit to lower extents, the dietary alkaloid induced the CYP1A2-preferential activity methoxyresorufin O-demethylase in all three tissues dose-dependently. Plasma nicotine concentration correlated neither with the dietary nor intake dose of the alkaloid nor with tissue levels of CYP1A, especially with the high-dose diet. Plasma nicotine levels at which CYP1A induction was maximal were comparable to those reported in smokers, suggesting that nicotine may induce CYP1A1 in humans.

Animals↗
PubMed1998

Does neurorehabilitation play a role in the recovery of walking in neurological populations?

This review demonstrates that neurorehabilitation approaches, based on recent neuroscience findings, can enhance locomotor recovery after a spinal cord injury or stroke. Findings are presented from more than 20 clinical studies conducted by numerous research groups on the effect of locomotor training using either body weight support (BWS), functional electrical stimulation (FES), pharmacological approaches or a combination of them. Among the approaches, only BWS-assisted locomotor training has been demonstrated to have a greater effect than conventional or locomotor training alone. However, when study results were combined and weighted for the number of subjects, the results indicated that there is a gradient of effects from small changes with the immediate application of FES or BWS to larger changes when locomotor training is combined with FES or BWS or pharmacological approaches. The findings of these studies suggest that these neurorehabilitation approaches do play a role in the recovery of walking in subjects with spinal cord injury or stroke. Several factors contribute to the potential for recovery including the site, etiology, and chronicity of the injury, as well as the type, duration, and specificity of the intervention and whether interventions are combined. Furthermore, how these neurorehabilitation approaches may take advantage of the plasticity process following neurological lesion is also discussed.

Exercise Therapy↗
PubMed1998

Outcome of liver transplantation in critically ill patients with alcoholic cirrhosis: survival according to medical variables and sobriety.

BACKGROUND: At our center from August 1989 to December 1992, 834 adults underwent orthotopic liver transplantation (OLT) using tacrolimus as the primary immunosuppressive agent. A total of 183 adults (22%) had alcohol-related liver disease. Patients with alcoholic cirrhosis had a better though not statistically significant 5-year survival rate compared with all other patients. We were interested in specific predictors of survival, particularly for alcoholic cirrhotics who were gravely ill at the point of transplantation. METHODS: For the 78 patients with alcohol-related liver disease who were United Network for Organ Sharing status IIA (critically ill) at the point of transplantation, variables of length of sobriety, alcohol rehabilitation, and medical variables (ventilator support, dialysis, vasopressor support, degree of encephalopathy, and infection) were assessed for contribution to survival. RESULTS: Although there was a trend toward poorer survival in patients with the shortest length of sobriety (< or =1 month), pre-OLT length of sobriety or alcohol rehabilitation did not predict survival. However, these patients tended to be in multiorgan failure and encephalopathic. Nevertheless, pre-OLT dialysis requirement was the only variable that predicted poorer survival (P < 0.002). This study was not designed to evaluate recidivism. However, we know that 24% of these patients have used alcohol at some point after OLT. CONCLUSIONS: Short pre-OLT length of sobriety may not predict which patients are likely to resume alcohol consumption after OLT, but it may identify patients in whom there will exist a variety of poor outcome variables. In our study, in these patients, post-OLT survival was associated with medical rather than alcohol history variables.

Adult↗
PubMed1998

Preimplantation diagnosis of the aneuploidies most commonly found in spontaneous abortions and live births: XY, 13, 14, 15, 16, 18, 21, 22.

The present preimplantation diagnosis test is able to screen for the most common aneuploidies from single blastomeres in about five hours with a 15 per cent misdiagnosis. This means that the risk of spontaneous abortion and trisomic offspring for women of advanced maternal age could be reduced to the same level as younger women for whom prenatal diagnosis is usually not necessary. Better probes and more fluorochromes could improve the success rate of the test.

Abortion, Spontaneous↗
PubMed1998

Activity of thoracic and lumbar epaxial extensors during postural responses in the cat.

This study examined the role of trunk extensor muscles in the thoracic and lumbar regions during postural adjustments in the freely standing cat. The epaxial extensor muscles participate in the rapid postural responses evoked by horizontal translation of the support surface. The muscles segregate into two regional groups separated by a short transition zone, according to the spatial pattern of the electromyographic (EMG) responses. The upper thoracic muscles (T5-9) respond best to posteriorly directed translations, whereas the lumbar muscles (T13 to L7) respond best to anterior translations. The transition group muscles (T10-12) respond to almost all translations. Muscles group according to vertebral level rather than muscle species. The upper thoracic muscles change little in their response with changes in stance distance (fore-hindpaw separation) and may act to stabilize the intervertebral angles of the thoracic curvature. Activity in the lumbar muscles increases along with upward rotation of the pelvis (iliac crest) as stance distance decreases. Lumbar muscles appear to stabilize the pelvis with respect to the lumbar vertebrae (L7-sacral joint). The transition zone muscles display a change in spatial tuning with stance distance, responding to many directions of translation at short distances and focusing to respond best to contralateral translations at the long stance distance.

Animals↗
PubMed1998

Preimplantation genetic analysis of translocations: case-specific probes for interphase cell analysis.

Carriers of balanced translocations show an increased risk of infertility and spontaneous abortions, because of errors in gametogenesis, and constitute a significant fraction of patients seeking assisted reproduction. The objective of this study was to design approaches for preimplantation diagnosis of chromosome translocations and to apply such techniques to the selection of chromosomally normal or balanced embryos prior to their transfer to the mother's womb. Three slightly different approaches were assessed by means of chromosome-specific, non-isotopically labeled DNA probes and an assay based on fluorescence in situ hybridization- to score and characterize chromosomes in single blastomeres biopsied from embryos on their third day of development. The three approaches were used for preimplantation genetic diagnosis involving four couples who had enrolled in our IVF program and in which one of the partners was a carrier of one of the following translocations: 46,XX,t(12;20)(p 13.1 ;q 13.3), 46,XY,t(3;4) (p24;p15), 45,XY,der(14;15)(10q;10q), and 46,XY,t(6;11) (p22.1;p15.3). A total of 33 embryos were analyzed, of which 25 (75.8%) were found to be either unbalanced or otherwise chromosomally abnormal. Only a single embryo could be transferred to patients A and D, whereas three embryos were transferred to patient B in a total of two IVF cycles. Transfer of two embryos to patient C resulted in an ongoing pregnancy. Re-analysis of non-transferred embryos with additional probes confirmed the initial results in 95% (20/21) of the cases. In conclusion, case-specific translocation tests can be applied to any translocation carrier for the selection of normal or chromosomally balanced embryos prior to embryo transfer. This is expected significantly to increase the success rates in IVF cycles of translocation carriers, while preventing the spontaneous abortion or birth of abnormal offspring.

Adult↗
PubMed1998

Will xenotransplantation ever be feasible?

In several recent conferences, the principal questions have been whether xenotransplantation technology should be encouraged and, if so, how it should be regulated. Because the prospect of successful transplantation of animal organs into humans is still remote, the rush to achieve consensus about clinical application would be inexplicable were it not for two ostensibly unrelated issues. The first is the small but undeniable theoretical hazard of causing new human infections with the intermingling of tissues from different species. The second, advanced by animal-rights advocates, concerns the spiritual and ethical relationship of humans to animals.

Animals↗
PubMed1998

Spectral imaging in preconception/preimplantation genetic diagnosis of aneuploidy: multicolor, multichromosome screening of single cells.

PURPOSE: Our purpose was to evaluate the utility of spectral imaging for multicolor, multichromosome enumeration in human interphase cell nuclei. METHODS: Chromosome-specific probes labeled with different fluorochromes or nonfluorescent haptens were obtained commercially or prepared in-house. Metaphase spreads, interphase lymphocytes, or blastomeres cells were hybridized with either 7 or 11 distinctly different probes. Following 46 hr of hybridization, slides were washed and detected using either a filter-based quantitative image processing system (QUIPS) developed in-house or a commercial spectral imaging system. RESULTS: The filter-based fluorescence microscope system is preferred for simultaneous detection of up to seven chromosome targets because of its high sensitivity and speed. However, this approach may not be applicable to interphase cells when 11 or more targets need to be discriminated. Interferometer-based spectral imaging with a spectral resolution of approximately 10 nm allows labeling of chromosome-specific DNA probes with fluorochromes having greatly overlapping emission spectra. This leads to increases in the number of fluorochromes or fluorochrome combinations available to score unambiguously chromosomes in interphase nuclei. CONCLUSIONS: Spectral imaging provides a significant improvement over conventional filter-based microscope systems for enumeration of multiple chromosomes in interphase nuclei, although further technical development is necessary in its application to embryonic blastomeres. When applied to preconception/preimplantation genetic diagnosis, presently available probes for spectral imaging are expected to detect abnormalities responsible for 70-80% of spontaneous abortions caused by chromosomal trisomies.

Aneuploidy↗
PubMed1998

Spontaneous abortions are reduced after preconception diagnosis of translocations.

PURPOSE: Preimplantation genetic diagnosis of translocations has seldom been attempted. Recently, a genetic test based on analyzing polar bodies at the methaphase stage, following fluorescent in situ hybridization with commercially available whole-chromosome painting DNA probes has been presented. Here we report the use of this method in seven couples in whom the female was a carrier of one of these balanced translocations: 45,XX,der (13q;14q)(q10;q10) (two cases), 46,XX,t(4;14)(p15.3;q24), 45,XX,der(14q;21q) (q10;q10), 46,XX,t(7;20)(q22;q11.2), 46,XX,t(9,11)(p24;q12), 46,XX,t(14;18)(q22;q11), and 46,XX,t(3;8)(q11;q11). METHODS: The original method was improved in two ways. First, centromeric probes for one or both chromosomes involved in the translocation were added to avoid misdiagnosis caused by possible confusion of first polar body monovalent chromosomes (with two chromatids each) with single chromatids. Second, for cases with terminal translocations where commercially available probes do not cover telomere sequences, a telomere probe labeling the translocated fragment was added. RESULTS: A total of 26 abnormal, 18 balanced, and 22 normal eggs was detected. Nine normal and seven balanced embryos were transferred, resulting in eight (50%) implanting, of which one spontaneously aborted. To date, the remainder have produced karyotypically normal or balanced babies and ongoing pregnancies. The rate of spontaneous abortions after preimplantation genetic diagnosis (12.5%) was significantly reduced (P < 0.001) compared to natural cycles in the same patients (95%). CONCLUSIONS: With the above improvements, the test can characterize any translocation of maternal origin and produce a high pregnancy rate and an apparently low frequency of spontaneous abortion.

Abortion, Spontaneous↗
PubMed1998

Induction of pulmonary CYP1A1 by nicotine.

1. We have examined the catalytic activities (7-ethoxyresorufin O-deethylase [EROD] and 7-methoxyresorufin O-demethylase [MROD]), protein levels (Western blot analysis) and mRNA levels (Northern blot analysis) of cytochrome P4501A (CYP1A1 and CYP1A2) in the lung, liver and kidney following a single 2.5 mg/kg (15.4 micromol/kg) subcutaneous dose of nicotine to the female Sprague-Dawley rat. 2. Only in lung microsomes was EROD activity significantly induced by nicotine treatment. The activity increased 4.4-fold at 6 h after treatment relative to controls, peaked at 12 h at 14.7-fold the control activity and returned to near control level at 24 h. 3. In parallel with EROD activity, CYP1A1 immunoreactive protein abundance was altered significantly by nicotine treatment only in the lung, peaking at 12 h and decreasing towards control levels thereafter. 4. Following subcutaneous nicotine treatment, CYP1A1 mRNA was detectable in the lung at 6 and 12 h but not at 24 h, was slightly elevated in the kidney at 12 h and was detectable in the liver only at the 12-h point. CYP1A2 immunoreactive protein and its mRNA were detectable only in the liver, and their levels were not affected significantly by nicotine pretreatment. 5. Nicotine affected the binding of Hepa 1c1c7 cytosolic protein to a CYP1A1 xenobiotic response element in a gel mobility shift assay, suggesting involvement of the aryl hydrocarbon receptor and transcriptional activation in CYP1A1 induction by the chemical. 6. Inhaled nicotine also induced pulmonary EROD activity, and the induction by either inhaled or injected nicotine was more pronounced in the male than in the female rat. 7. The findings show that nicotine is a potent, rapid but transient inducer of CYP1A1 in the rat lung and suggest that the alkaloid is a likely contributor to CYP1A1 induction by cigarette smoke.

Administration, Inhalation↗
PubMed1998

Control of stance during lateral and anterior/posterior surface translations.

The purpose of this study was to compare and contrast postural responses to lateral and A/P surface translations by quantifying joint positions, bilateral three-dimensional (3-D) ground reaction forces, and lower limb and trunk muscle electromyographic (EMG) activity. Subjects stood on a movable platform which was randomly translated in four different directions. The kinematic patterns in response to lateral and anterior/posterior (A/P) surface translations were similar in that there was a sequential displacement and reversal of the shank/thigh and then trunk segments. While the body center of mass (CoM) was displaced equally in response to lateral and A/P translations, equilibrium was maintained by redistributing the vertical forces and changing the shear forces exerted against the support surface. These force responses were bilaterally symmetrical for A/P translations but not for lateral translations. With respect to EMG activity, the first muscle activated was the proximal tensor fascia latae for lateral translations whereas the distal muscles were recruited first for A/P translations. Results from this study suggest that control of postural equilibrium may be similar for A/P and lateral translations, although specific differences in patterns may reflect various biomechanical constraints of the trunk and the lower extremities associated with the two planes of movement.

Adult↗
PubMed1998

EMG responses to maintain stance during multidirectional surface translations.

To characterize muscle synergy organization underlying multidirectional control of stance posture, electromyographic activity was recorded from 11 lower limb and trunk muscles of 7 healthy subjects while they were subjected to horizontal surface translations in 12 different, randomly presented directions. The latency and amplitude of muscle responses were quantified for each perturbation direction. Tuning curves for each muscle were examined to relate the amplitude of the muscle response to the direction of surface translation. The latencies of responses for the shank and thigh muscles were constant, regardless of perturbation direction. In contrast, the latencies for another thigh [tensor fascia latae (TFL)] and two trunk muscles [rectus abdominis (RAB) and erector spinae (ESP)] were either early or late, depending on the perturbation direction. These three muscles with direction-specific latencies may play different roles in postural control as prime movers or as stabilizers for different translation directions, depending on the timing of recruitment. Most muscle tuning curves were within one quadrant, having one direction of maximal activity, generally in response to diagonal surface translations. Two trunk muscles (RAB and ESP) and two lower limb muscles (semimembranosus and peroneus longus) had bipolar tuning curves, with two different directions of maximal activity, suggesting that these muscle can play different roles as part of different synergies, depending on translation direction. Muscle tuning curves tended to group into one of three regions in response to 12 different directions of perturbations. Two muscles [rectus femoris (RFM) and TFL] were maximally active in response to lateral surface translations. The remaining muscles clustered into one of two diagonal regions. The diagonal regions corresponded to the two primary directions of active horizontal force vector responses. Two muscles (RFM and adductor longus) were maximally active orthogonal to their predicted direction of maximal activity based on anatomic orientation. Some of the muscles in each of the synergic regions were not anatomic synergists, suggesting a complex central organization for recruitment of muscles. The results suggest that neither a simple reflex mechanism nor a fixed muscle synergy organization is adequate to explain the muscle activation patterns observed in this postural control task. Our results are consistent with a centrally mediated pattern of muscle latencies combined with peripheral influence on muscle magnitude. We suggest that a flexible continuum of muscle synergies that are modifiable in a task-dependent manner be used for equilibrium control in stance.

Adult↗
PubMed1998

Comparison of tacrolimus absorption in transplant patients receiving continuous versus interrupted enteral nutritional feeding.

OBJECTIVE: To determine the effect of enteral nutritional feeding on the absorption of tacrolimus administered through a nasoduodenal tube to organ transplant patients. METHODS: A nonrandomized, prospective study of tacrolimus absorption was performed in 10 liver or lung transplant patients who received Osmolite enteral nutrition through a nasoduodenal feeding tube. Multiple blood samples were collected just prior to and at 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 12 hours after nasoduodenal administration of tacrolimus on 2 consecutive days, once when tacrolimus was administered along with the continuous enteral feeding and the other time when the enteral feeding was withheld 1 hour prior to and 8 hours after tacrolimus administration, to assess tacrolimus absorption. The whole blood tacrolimus concentrations were measured by the microparticulate enzyme immunoassay method. Pharmacokinetic parameters between the two time periods were compared by using a paired t-test at a significance level of a p value of 0.05 or less. RESULTS: The time to reach peak blood concentrations (p = 0.055), dose-normalized trough concentrations (p = 0.617), maximum blood concentrations (p = 0.197), and dose-normalized AUC (p = 0.755) were not significantly different between two study periods. CONCLUSIONS: This study demonstrated that simultaneous administration of Osmolite enteral feedings with tacrolimus did not interfere with tacrolimus absorption in transplant patients.

Absorption↗
PubMed1998

Causes of death in autopsied liver transplantation patients.

Liver transplantation is an established treatment for multiple end-stage liver diseases, yet little information is available on the autopsy-determined causes of death in liver transplant recipients. We undertook a retrospective study of the immediate causes of death in all liver transplant recipients who underwent autopsy at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, from January 1982 to January 1997. Infections were the most frequent cause of death, present in 64% of a total of 321 cases. Overall, the infections were bacterial in 48% of the cases, fungal in 22%, and viral in 12%. The ratio of infectious to noninfectious causes of death did not change significantly during the 15-year study period, and the relative percentages of bacterial, fungal, and viral infections showed relatively little variation on a year-to-year basis. Two-thirds of all infections occurred during the first 100 days post transplantation. A precipitous drop in the number of infections (and the number of deaths) occurred by Day 90. Other major causes of death included liver failure (12%), pulmonary failure (10%), multiple organ system (8%), and cardiovascular causes (6%). Infections were the most frequent cause of death in this study population, suggesting that improvement in the prevention and treatment of infections is an important way to improve survival of liver transplant recipients.

Adolescent↗