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Biomedical subjects

J Chen

Publications and source records attributed to J Chen.

At least 847 records · Page 47Linked to original sources

Acceleration of P/C-type inactivation in voltage-gated K(+) channels by methionine oxidation.

Oxidation of amino acid residues causes noticeable changes in gating of many ion channels. We found that P/C-type inactivation of Shaker potassium channels expressed in Xenopus oocytes is irreversibly accelerated by patch excision and that this effect was mimicked by application of the oxidant H(2)O(2), which is normally produced in cells by the dismutase action on the superoxide anion. The inactivation time course was also accelerated by high concentration of O(2). Substitution of a methionine residue located in the P-segment of the channel with a leucine largely eliminated the channel's sensitivity to patch excision, H(2)O(2), and high O(2). The results demonstrate that oxidation of methionine is an important regulator of P/C-type inactivation and that it may play a role in mediating the cellular responses to hypoxia/hyperoxia.

Animals↗

Decreased neural crest stem cell expansion is responsible for the conotruncal heart defects within the splotch (Sp(2H))/Pax3 mouse mutant.

OBJECTIVE: Several mouse models of cardiac neural crest cell (NCC)-associated conotruncal heart defects exist, but the specific cellular and molecular defects within cardiac NCC morphogenesis remain largely unknown. Our objective was to investigate the underlying mechanisms resulting in outflow tract defects and why insufficient cardiac NCC reach the heart of the Splotch (Sp(2H)) mouse mutant embryo. METHODS: For this study we used in vitro cell culture techniques, in vivo mouse-chick chimeras, BrdU cell proliferation labeling, TUNEL labeling to visualize apoptosis and the molecular markers AP-2, Wnt-1 and Wnt-3a to characterize NCC morphogenesis in vivo. RESULTS: Expression of the NCC marker AP-2 revealed an extensive reduction in migratory NCC, however the rates of cell proliferation and apoptosis were unaffected, and do not account for the Sp(2H) NCC-associated heart defects. Further expression analysis revealed that Wnt-1, but not Wnt-3a, is expressed at decreased levels within Sp(2H) and that the cardiac NCC fail to undergo normal NC stem cell proliferative expansion prior to migration while still in the neural folds. However, when placed into a wild-type matrix or a tissue culture environment, the Sp(2H) cardiac NCC could migrate normally. Additionally, this reduced population of Sp(2H) NC stem cells do migrate properly within the Sp(2H) environment, as observed by neurofilament expression and cardiac innervation. CONCLUSIONS: Taken together, all these data indicate that the Sp(2H) defect is intrinsic to the NC stem cells themselves and that there is a decrease in the number of pre-migratory cardiac NCC that form. It appears that this decrease in NCC number is the primary defect that ultimately leads to a lack of a cardiac NCC-derived Sp(2H) outflow tract septum.

Animals↗

Dynamics of wavelets and their role in atrial fibrillation in the isolated sheep heart.

BACKGROUND: The multiple wavelet hypothesis is the most commonly accepted mechanism underlying atrial fibrillation (AF). However, high frequency periodic activity has recently been suggested to underlie atrial fibrillation in the isolated sheep heart. We hypothesized that in this model, multiple wavelets during AF are generated by fibrillatory conduction away from periodic sources and by themselves may not be essential for AF maintenance. METHODS AND RESULTS: We have used a new method of phase mapping that enables identification of phase singularities (PSs), which flank individual wavelets during sustained AF. The approach enabled characterization of the initiation, termination, and lifespan of wavelets formed as a result of wavebreaks, which are created by the interaction of wave fronts with functional and anatomical obstacles in their path. AF was induced in six Langendorff-perfused sheep hearts in the presence of acetylcholine. High resolution video imaging was utilized in the presence of a voltage sensitive dye; two-dimensional phase maps were constructed from optical recordings. The major results were as follows: (1) the critical inter-PS/wavelet distance for the formation of rotors was 4 mm, (2) the spatial distribution of wavelets/PSs was non-random. (3) the lifespan of PSs/wavelets was short; 98% of PSs/wavelets existed for < 1 rotation, and (4) the mean number of waves that entered our mapping field (15.7 +/- 1.6) exceeded the mean number of waves that exited it (9.7 +/- 1.5; P < 0.001). CONCLUSIONS: Our results strongly suggest that multiple wavelets may result from breakup of high frequency organized waves in the isolated Langendorff-perfused sheep heart, and as such are not a robust mechanism for the maintenance of AF in our model.

Acetylcholine↗

Intestinal inflammation observed in IL-2R/IL-2 mutant mice is associated with impaired intestinal T lymphopoiesis.

BACKGROUND & AIMS: Although interleukin (IL)-2(-/-) and IL-2Ralpha(-/-) mice develop inflammatory bowel disease, IL-2Rbeta(-/-) animals are apparently free of gut pathology. Intraintestinal T lymphopoiesis is reported to be impaired in IL-2Rbeta(-/-) mice; we have determined whether this characteristic correlated with the apparent resistance of this mutant strain to intestinal inflammation. This led us to reassess intraintestinal T lymphopoiesis in these 3 mutant strains. METHODS: Intestinal histology and intraintestinal T lymphopoiesis were analyzed in unmanipulated mutant mice and in athymic and euthymic radiation chimeras reconstituted with bone marrow derived from IL-2(-/-), IL-2Ralpha(-/-), and IL-2Rbeta(-/-) donors. RESULTS: Intraintestinal T lymphopoiesis was ablated in the 3 mutant strains and was associated with cryptopatch abnormalities. The intestinal mucosa of mice reconstituted with lymphocytes from IL-2Rbeta(-/-) mice exhibited lesions of both the small and large bowel similar to those observed in the early stages of human gluten enteropathy and acute ulcerative colitis, respectively. Analysis of euthymic and athymic bone marrow radiation chimeras indicated that T cells located in the intestinal mucosa of unmanipulated IL-2(-/-), IL-2Ralpha(-/-), and IL-2Rbeta(-/-) mice are of thymic origin. CONCLUSIONS: Null mutations at IL-2/IL-2Ralpha and beta loci differentially affect intraintestinal and intrathymic T lymphopoiesis. These conditions are associated with lesions of intestinal inflammation that are mediated by thymus-derived T cells.

Animals↗

A biomechanical model of Peyronie's disease.

Peyronie's disease is a pathological condition of the penis which is characterized by localized ossification of the tunica albuginea. A common symptom of the chronic stage is penile deformity during erection, which is frequently associated with pain and erectile dysfunction. A two-dimensional biomechanical model of the penis was applied to study the development of Peyronie's disease by simulating the mechanical stress distribution which would result from the interaction of the ossified tunical tissue with other penile soft tissues. The model was solved by using commercial finite element software for a characteristic erectile pressure. The results demonstrate that Peyronie's plaques may induce intensified stresses around the penile nerves and blood vessels, up to double those in the normal penis. These elevated stresses may cause a painful sensation of neural origin or ischemia in regions of compressed vascular tissue. Severe penile deformities have been shown to develop if Peyronie's plaques develop only around one of the corpora cavernosa due to the non-homogeneous resistance of the tunica to expansion during erection. The present model can be clinically applied as an aid in the planning process of reconstructive surgery or insertion of a prosthesis.

Biomechanical Phenomena↗

Activation of group I metabotropic glutamate receptors induces long-term depression at sensory synapses in superficial spinal dorsal horn.

Low-frequency stimulation of primary afferent Adelta-fibers can induce long-term depression of synaptic transmission in rat superficial spinal dorsal horn. Here, we have identified another form of long-term depression in superficial spinal dorsal horn neurons that is induced by specific group I but not group II metabotropic glutamate receptor (mGluR) agonists. Synaptic strength between Adelta-fibers and dorsal horn neurons was examined by intracellular recordings in a spinal cord-dorsal root slice preparation from young rat. In the presence of bicuculline and strychnine, bath application of (1S,3R)-1-aminocyclopentane-1, 3-dicarboxylic acid ((1S,3R)-ACPD) or the specific group I mGluR agonist (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) but not the specific group II mGluR agonist (2S,2'R,3'R)-2-(2', 3'-dicarboxycyclopropyl)glycine (DCG-IV) for 20 min produced an acute and a long-term depression of synaptic strength. Bath application of the N-methyl-D-aspartate receptor antagonist D-2-amino-5-phosphonovaleric acid did not affect these depressions by (1S,3R)-ACPD. After pre-incubation of slices with pertussis toxin, a G-protein inhibitor, (1S,3R)-ACPD still induced acute and long-term depressions. The phospholipase C inhibitor U73122 stereoselectively blocked the induction of long-term depression without affecting acute synaptic inhibition. This study demonstrates that, in the spinal cord, direct activation of group I mGluRs that are coupled to phospholipase C through pertussis toxin-insensitive G-proteins induces a long-term depression of synaptic strength. This may be relevant to the processing of sensory information in the spinal cord, including nociception.

Animals↗

Behavioral evidence for brain-based ability factors in visuospatial information processing.

The present study examined possible parallels between the structure of human visuospatial abilities and the organization of the neural systems. Forty-eight participants were tested on seven speeded visuospatial tasks. Three of these tasks were constructed so as to rely primarily on known ventral stream functions and four were constructed so as to rely primarily on known dorsal stream functions. Both sets of tasks spanned approximately the same range of difficulty as indexed by both the speed and accuracy of decision making. Factor analysis of response times on the seven tasks revealed only two significant factors. The putative ventral stream tasks all loaded heavily on one factor (mean loading=0.843) but only weakly on the other factor (mean loading=0.222); the putative dorsal stream tasks showed the opposite pattern in that they all loaded heavily on the second factor (mean loading=0.828) but only weakly on the first factor (mean loading=0.229). These findings are consistent with the hypothesis that human visuospatial abilities can be classified using categories based on the specializations of underlying neural structures and systems.

Adult↗

Minor diarylheptanoid glycosides of Alnus rubra bark.

The diarylheptanoid (S)-1,7-bis-(4-hydroxyphenyl)-heptan-3-one-5-O-beta-D-xylopyranosi de, and two known compounds, 1,7-bis-(3,4-dihydroxyphenyl)-heptan-3-one-5-O-beta-D-glucopyranos ide and platyphylloside were isolated from Alnus rubra bark. Structures were established by application of spectrometric techniques.

Benzene Derivatives↗

Cellular mechanisms involved in rabbit carotid body excitation elicited by endothelin peptides.

The present study evaluated the effects of endothelin (ET) peptides on carotid sinus nerve (CSN) activity, catecholamine (CA) release, and second messenger signaling pathways in rabbit carotid bodies superfused in vitro, and in dissociated chemosensory type I cells. ET-1 (1.0 microM) and ET-3 (1.0 microM) did not alter basal CSN activity and CA release, but they potentiated nerve activity (P<0. 05) and CA release (P<0.05) evoked by hypoxia. Under basal conditions, ET-1 and ET-3 (1.0 microM each) elevated tissue cyclic AMP (cAMP) levels nearly 3-fold (P<0.001, ET-1; P<0.05, ET-3) and inositol phosphate (IP(n)) levels nearly 4-fold (P<0.01, ET-1). Hypoxia evoked an increase in carotid body cAMP, and this response was also potentiated in the presence of 1.0 microM ET-1 (P<0.01) or 1.0 microM ET-3 (P<0.001). Patch-clamp studies of isolated type I cells showed that 100 nM ET-1 elevated the peak amplitude of voltage-sensitive (L-type) Ca(2+)-currents by an average of 37.6% (P<0.001). Fluorescent Ca(2+)-imaging revealed that 100 nM ET-1 did not alter [Ca(2+)](i) under basal conditions, but that [Ca(2+)](i)-responses evoked by hypoxia were potentiated by 87% (P<0. 01). Our data indicate that ET augments chemoreceptor responses by activating second messenger signaling pathways which promote the phosphorylation of Ca(2+)-channel protein, thereby enhancing stimulus-evoked intracellular Ca(2+) levels.

Animals↗

The use of PLS algorithms and quantum chemical parameters derived from PM3 hamiltonian in QSPR studies on direct photolysis quantum yields of substituted aromatic halides.

The Partial Least-Squares (PLS) method was used to further study Quantitative Structure-Property Relationship (QSPR) for photohydrolysis quantum yields of selected aromatic halides. The cluster of substituted bromobenzenes and iodobenzenes was further grouped into two clusters, substituted bromobenzenes and substituted iodobenzenes, for which QSPRs were obtained, respectively. The QSPRs obtained by PLS are more significant than those obtained in previous studies. The studies showed that only when the compounds belonging to different groups are studies separately, inherent relationships between molecular properties and their structure characteristics can be revealed. It can be generally concluded that the photohydrolysis quantum yields of the substituted aromatic halides are dependent on the overall characters of the molecules, the characters of the carbon-halogen bonds to be broken in the photolysis, and the character of the halogen atoms to be replaced in the photolysis. Electronegativity has great relevance to the photohydrolysis processes of the compounds. Substituted aromatic halides with large average molecular polarizability and molecular weight values tend to have low photolysis quantum yields.

Algorithms↗

Teflon granuloma after microvascular decompression for trigeminal neuralgia.

BACKGROUND: Our purpose was to research the factors that may induce Teflon granuloma in trigeminal neuralgia patients who have undergone microvascular decompression (MVD) procedures, to propose methods for the early diagnosis of Teflon granuloma, and provide suggestions for reducing this complication. METHODS: From 1985 to 1996, 89 trigeminal neuralgia patients underwent MVD with Teflon felt to separate the offending vessels and the trigeminal nerve. Ten patients had secondary explorations for recurrent symptoms. Five patients developed recurrent facial pain associated with facial numbness within a certain period after the first operation. We reviewed the onset and site of the initial symptoms, the duration of the symptoms, the operative findings and methods, and the results of the operations. In the reoperative patients, we analyzed the initial and secondary symptoms after the first operation, and the time to relapse. We compared the operative findings and methods in these operations. RESULTS: The operative findings in the 10 patients with recurrence were Teflon granuloma in five patients, arterial loop compression in three patients, venous compression in one patient, and negative exploration in one patient. The Teflon granuloma patients all complained of facial numbness after the first MVD operation. The incidence of Teflon granuloma after MVD was 5.6% (5/89). CONCLUSION: The Teflon felt used in the MVD procedure can produce complications. It is not absolutely inert when used in MVD procedures. When it contacts the tentorium and/or dura, an inflammatory giant-cell foreign body reaction can be induced. In the future, we should search for other implants to replace the Teflon felt. However, until new materials are found, we suggest that the Teflon felt be kept away from the tentorium and dura and placed completely within the CSF cisterna. We can diagnose Teflon granuloma early with enhanced CT and/or MRI, especially in patients with new facial numbness symptoms after Teflon MVD procedures. The results of reexploration of Teflon granulomas are more satisfactory than a negative exploration or venous compression. We may be able to decrease the incidence of Teflon granuloma. We should be more aggressive in performing reexploration in these recurrent patients.

Adult↗

Circulating adhesion molecules and neutral endopeptidase enzymuria in patients with urolithiasis and hydronephrosis.

OBJECTIVES: To measure the concentrations of adhesion molecules (intercellular adhesion molecule-1 ¿ICAM-1, E-selectin, and L-selectin) in the serum of patients with renal stones and patients with hydronephrosis caused by obstructive ureteral stones. Renal tubular enzymes were examined from their urine samples to evaluate whether neutral endopeptidase (NEP) behaved as traditional tubular enzyme markers (N-acetyl-beta-glucosaminidase ¿NAG and beta-galactosidase ¿beta-GAL) in their disease state. METHODS: Three groups were studied. Group 1 included 15 normal volunteers, group 2 included 12 patients with ureteral stones and ipsilateral hydronephrosis, and group 3 included 17 patients with renal stones in one kidney without hydronephrosis or hydrocalycosis. A single, overnight fasting blood and urine sample was collected from each subject. Serum levels of ICAM-1, E-selectin, and L-selectin were measured by enzyme-linked immunosorbent assay. NEP, NAG, and beta-GAL were measured from urine samples, and the enzyme activities were expressed per gram of creatinine. RESULTS: Serum levels of ICAM-1 were higher in groups 2 and 3 (522 +/- 95 and 329 +/- 42 ng/mL, respectively), but the differences were only significant between group 2 and group 1 (263 +/- 32 ng/mL) and group 2 and group 3 (P <0.05). Serum levels of L-selectin were lower in group 3 and were significantly different when compared with groups 1 and 2 (P <0. 05). The serum levels of E-selectin were not significantly different among these three groups. Urinary levels of NEP were lower in group 2, although the levels of NAG and beta-GAL were more elevated than in group 1. CONCLUSIONS: Serum levels of ICAM-1 were elevated in patients with unilateral hydronephrosis caused by a ureteral stone, and E-selectin and L-selectin levels did not change significantly. These findings suggest that ICAM-1 may play a role in renal immune injury to ureteral obstruction. The urinary NEP values were lower in patients with hydronephrosis caused by ureteral stones, and the traditional lysosomal enzymes were increased. The lower urinary NEP values might suggest impairment of ipsilateral renal function. Renal stones per se resulted in no significant changes in serum adhesion molecule levels, although the levels of L-selectin were significantly decreased.

Cell Adhesion Molecules↗

Is a second injection of vasoactive medication necessary during color duplex doppler evaluation of young patients with veno-occlusive erectile dysfunction?

OBJECTIVES: To assess the contribution of a second injection of vasoactive medication into the corpus cavernosum during the duplex Doppler study for evaluation of young patients with vasculogenic erectile dysfunction (ED). METHODS: Thirty-five patients, 23 to 50 years old (median age 43), clinically diagnosed as having veno-occlusive ED underwent a color duplex Doppler study. The peak systolic velocity, end-diastolic velocity, resistance index, and arterial diameter measurements were obtained from both cavernosal arteries before and 2, 5, 10, and 20 minutes after an intracavernous injection of a vasoactive drug. All patients were reinjected with similar doses of the same medication, and all measurements were repeated. The erection quality was estimated 20 minutes after each injection. RESULTS: The peak systolic velocity after the second injection was significantly higher statistically than after the first injection (P <0.02). No differences in end-diastolic velocity, resistance index, arterial diameter, or the evaluated side between the first and second injections were found. CONCLUSIONS: A single injection of vasoactive drugs can provide sufficient information on the arterial and veno-occlusive mechanism during color duplex Doppler evaluation of young patients with vasculogenic ED without compromising the quality of the evaluation. Limiting the number of injections to only one may prevent adverse reactions caused by the second injection and reduce the cost and duration of this test.

Adult↗

Chemical gradient in plasma-sprayed HA coatings.

The microstructure and inhomogeneous features of plasma-sprayed hydroxyapatite coatings on titanium substrates have been examined using the time-of-flight secondary ion mass spectroscopy (ToF-SIMS), micro-Raman spectroscopy and nano-indentation techniques. The crystalline and amorphous areas in coatings can be identified by the elastic modulus difference. The concentration gradient of O and OH ions was detected in the through-thickness direction of coatings. Lack of O and OH ions near the titanium interface implies the existence of phases other than HA, and might result in excessive adsorption of the coatings near the interface in HA-coated Ti implants.

Alloys↗

Genetic regulation of primitive hematopoietic stem cell senescence.

OBJECTIVE: To define effects of strain on PHSC (primitive hematopoietic stem cells) senescence (decline in function with age) in vivo, and to map a locus that regulates PHSC senescence. MATERIALS AND METHODS: Long-term function and self-renewal were compared in bone marrow cells (BMC) from old and young mice of three strains: BALB/cBy (BALB), DBA/2 (D2) and C57BL/6 (B6), using competitive repopulation and serial transplantation in vivo. BMC from each old or young donor were mixed with standard doses of congenic, genetically marked BMC and transplanted into lethally recipients. Percentages of donor-type erythrocytes and lymphocytes in the recipients determined the functional ability of donor PHSC relative to the standard, where one repopulating unit (RU) of donor BMC equals the repopulating ability of 100,000 standard competitor BMC. Using similar techniques, repopulating abilities of old and young recombinant inbred (RI) donors of 12 strains derived from BALB and B6 were compared in NK-depleted BALBxB6 Fl recipients to map a locus that appears to have a major role in PHSC senescence. RESULTS: PHSC function declined about 2 fold with age in BALB and D2 BMC, and increased more than 2-fold with age in B6 BMC, with all old/young strain differences significant, p<.01. Ten months after serial transplantation, young B6, BALB, and D2 PHSC had self-renewed 1.6-, 4.2-, and 3.2-fold better than old, with BALB and D2 old/young differences p<.01. Young B6 PHSC self-renewed 1.9- and 2.9-fold better than young BALB and D2 PHSC. The PHSC senescence phenotypes (old/young RU ratios) for 12 CXB RI strains suggested a genetic linkage to D12Nyul7 on Chromosome 12. CONCLUSION: PHSC senescence is genetically regulated, and is much delayed in the B6 strain compared to the BALB and D2 strains. A locus on Chromosome 12 may regulate PHSC senescence.

Aging↗

An experimental study on systemic inflammatory response syndrome induced by subeschar tissue fluid.

OBJECTIVE: To investigate the biological activity of subeschar tissue fluid (STF) and its probable mechanism in the genesis of systemic inflammatory response syndrome(SIRS). METHODS: The changes of heart rate (HR), respiratory rate (RR), white blood cell count (WBCC) as well as the major organ function were observed in the animals injected with STF. The inflammatory mediators TNF-alpha and IL-1 in the supernatants of macrophages cultured with STF were assayed. RESULTS: The HR, RR and WBCC were elevated in animals after injection with STF. STF showed a deleterious effect on function and structure of the major visceral organs. Macrophages were activated to produce excessive TNF-alpha and IL-1. CONCLUSION: The findings suggest that STF may be one of the inducing factors involved in the genesis of SIRS and the development of MODS in the early postburn stage.

Animals↗

Induction of homosynaptic long-term depression at spinal synapses of sensory a delta-fibers requires activation of metabotropic glutamate receptors.

The synaptic strength between primary afferent Adelta-fibers, many of which convey pain-related information, and second order neurons in the spinal dorsal horn can be depressed for prolonged periods of time in a use- and N-methyl-D-aspartate receptor-dependent fashion. Here, we have used a transverse spinal cord slice-dorsal root preparation of young rat to characterize the nature of this form of long-term depression and the role of metabotropic glutamate receptors. Dorsal roots were bisected and intracellular recordings were made from lamina II neurons with independent excitatory synaptic inputs from both dorsal root halves. Conditioning stimulation of one dorsal root half (1 Hz, 900 pulses) induced long-term depression that was specific for the stimulated pathway, i. e. homosynaptic in nature. The induction of long-term depression was prevented by non-selective group I and group II mGluR antagonist (S)-alpha-methyl-4-carboxyphenylglycine, by selective group I receptor antagonist (S)-4-carboxyphenylglycine and by selective group II mGluR antagonist (RS)-alpha-methylserine-O-phosphate monophenyl ester. Group III mGluR antagonist (RS)-alpha-methylserine-O-phosphate was ineffective. Short-term depression was not affected by any of these antagonists.Thus, a homosynaptic form of long-term depression exists at putative nociceptive synapses in the spinal dorsal horn and its induction requires the activation of both group I and II metabotropic glutamate receptors.

Animals↗