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Biomedical subjects

J Kong

Publications and source records attributed to J Kong.

At least 55 records · Page 3Linked to original sources

Spectroelectrochemical investigation of direct electron transfer between resting horseradish peroxidase and its oxidation states promoted by DNA.

Direct electron transfer between resting horseradish peroxidase (HRP) and its oxidation states was observed at a gold mesh electrode in a spectroelectrochemical cell in the presence of DNA. The conversion between HRP and the oxidized species induced electrochemically was found to be reversible and parallel to that initiated chemically. DNA played an important role as electron carrier and promoted the electron transfer between HRP and the electrodes. Voltammetric results and CD spectra indicated an interaction between HRP and DNA. Moreover, the secondary structure of HRP was slightly disturbed upon mixing with DNA. The direct spectroelectrochemistry of HRP at a gold mesh electrode presented new information on its bioelectrochemical characteristics.

Circular Dichroism↗

Early-latency somatosensory evoked potentials elicited by electrical acupuncture after needling acupoint LI-4.

The stimulating methods of prior studies on somatosensory evoked potentials (SEPs) elicited by acupoint stimulus had involved surface electrodes, while the clinical practice of acupuncture is mostly performed by inserting the acupuncture needle inside the body. Clinical observations show that there are often some special sensations when LI-4 is needled. To observe if the SEPs produced by acupoint acupuncture had a distinguishing property, we studied the SEPs elicited by electrical acupuncture after the acupuncture needle was inserted into LI-4 and its control point, and then mapped them with the 128-channel Electric Brain Signal Image system. We also compared this to SEPs by median nerve stimuli. Results showed that the most interesting finding was the marked differences of N1-P1 and N2-P2 amplitude between SEPs at LI-4 (SEP-LI) and its control point (SEP-CP), which were in the opposite direction. Marked differences were also found between latencies and amplitudes of the SEPs elicited by acupuncture and by median nerve stimulus (SEP-M). The differences between SEP-LI and SEP-CP might be due to the additional effects of the activation of nerve endings and muscle spindles in LI-4 to the SEPs formed by the activation of superficial and deep radial nerves during electrical acupuncture. The differences between SEPs to acupoint and median nerve stimuli might be mainly due to the different distances from the stimulated regions to the cerebral cortex, the diversity and the number of activated fibers.

Acupuncture Points↗

Early lesions of cerebral atherosclerosis from induced hypertension in Watanabe heritable hyperlipidemic rabbits.

Watanabe heritable hyperlipidemic (WHHL) rabbits are well known to develop severe atherosclerotic lesions in extracranial arteries but not in cerebral arteries. In the present work we produced and investigated atherosclerotic lesions in cerebral arteries of WHHL rabbits by inducing hypertension. Hypertension was induced by right nephrectomy and surgically induced stenosis of the left renal artery. Six months after surgery the rabbits were killed for morphologic, immunohistochemical and transmission electron microscopic studies of extracranial and cerebral atherosclerosis. A significant rise in systolic blood pressure was evident 3 months after surgery in the hypertensive group (p < .001). Atherosclerotic lesions had developed areas near the vertebral-basilar arterial confluence and the circle of Willis in the hypertensive Watanabe rabbits by 6 months after surgery (p < .001). Atherosclerotic lesions in cerebral arteries remained less severe than in the aorta and coronary arteries, and showed qualitative morphologic differences. This is the first report of production by hypertension of experimental cerebral atherosclerosis in the WHHL rabbits, indicating that hypertension as well as hyperlipidemia was required for development of lesions in cerebral arteries. This model should be useful for studying development of cerebral atherosclerosis and may contribute to improved prevention and treatment of the human disease.

Animals↗

Gate-Controlled Superconducting Proximity Effect in Carbon Nanotubes.

The superconducting proximity effect in single-walled carbon nanotubes connected to niobium electrodes was controlled with the use of nearby gates that tune the niobium-nanotube transparency. At 4.2 kelvin, when the transparency was tuned to be high, a dip in the low-bias differential resistance was observed, indicating a proximity effect mediated by Andreev reflection. When the transparency was tuned to be low, signatures of Andreev reflection disappeared and only tunneling conduction was observed. Below approximately 4 kelvin, a narrow peak in differential resistance around zero bias appeared superimposed on the Andreev dip, probably as a result of electron-electron interaction competing with the proximity effect.

Journal Article↗

Peripheral axotomy slows motoneuron degeneration in a transgenic mouse line expressing mutant SOD1 G93A.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that involves motoneuron degeneration, paralysis, and death. Mutations in Cu, Zn superoxide dismutase (SOD1) are one cause of this disease. It has been a puzzle as to why mutations in SOD1, an enzyme expressed in many neuronal types, selectively kill motoneurons. To begin to explore the factors that determine this selectivity, we carried out peripheral axotomy in mice expressing a mutant SOD1 (G93A mice) and controls (nontransgenic mice and mice expressing wild-type human SOD1). Axotomy in controls induced a predicted axonal atrophy and a small degree of axon loss. The axonal atrophy led to an increase in the number of small axons and a decrease in the number of large axons. In contrast to the controls, axotomy in G93A mice reduced the extent of axon degeneration at the end stage of the disease, leading to an increase in the number of surviving motor axons. Interestingly, all of the increased surviving axons were in the axon group with diameters smaller than 4.5 microm. This result suggests an apparent threshold of vulnerability that is correlated with axon size.

Amino Acid Substitution↗

Dystrophin is required for organizing large acetylcholine receptor aggregates.

Dystrophin is a cytoplasmic protein underlying the plasma membrane in normal skeletal muscle. Its absence leads to muscle degeneration as seen in Duchenne muscular dystrophy (DMD) and in mdx mice. One puzzling question in the study of dystrophinopathies is that in mdx muscles the neuromuscular junctions (NMJs) show little, if any, developmental defect, but morphological and functional abnormalities of NMJs are obvious after muscle damage and regeneration begin. This phenomenon leads us to hypothesize that dystrophin may be required for endplate maintenance and/or endplate remodeling in regenerating fibers. Here we show that the absence of dystrophin causes NMJ fragmentation in adult muscle fibers, and greatly reduces both spontaneous and agrin-induced acetylcholine receptor (AChR) clustering activities on cultured myotubes derived from satellite cells. The lower AChR clustering in mdx myotubes originates in the smaller size of each cluster and from a 72% reduction in the occurrence of large (> 10 micron 2) AChR clusters. Our results suggest dystrophin is involved in organizing small AChR clusters into large AChR aggregates during muscle regeneration, although it is not required for initiating the original AChR clustering activity.

Age Factors↗

Electrochemical generation of ferrylmyoglobin during oxidation of styrene with films of DNA and a poly (ester sulfonic acid) ionomer.

The chemistry of electrochemically-driven myoglobin-catalyzed oxidation of styrene was investigated in films of DNA or Eastman AQ ionomer on optically transparent electrodes. Conversion of styrene to styrene oxide proceeded via a ferrylmyoglobin radical intermediate. Ferrylmyoglobins were clearly detected by spectroelectrochemistry in films of 1-4 mm thick. The ferrylmyoglobin radical is produced by reaction of metmyoglobin (Mb) in the films with hydrogen peroxide formed by electrochemical catalytic reduction of oxygen catalyzed by Mb. Thus, electrochemically-driven styrene oxidation with these films proceeds by a 'doubly catalytic' electrode-driven reduction-oxidation pathway. Ferrylmyoglobin formation during electrolysis of Mb-DNA films in aerobic solutions was much faster, and styrene oxidation occurred with less Mb decomposition compared to the Mb-AQ films. The better performance of Mb-DNA films is correlated with a larger fraction of electroactive Mb and better stability than for the Mb-AQ films.

Animals↗

Brain potentials during mental arithmetic-effects of problem difficulty on event-related brain potentials.

One addend '+' symbol and another addend were presented in sequence to subjects in a monitor, and event-related brain potentials (ERPs) were recorded at the same time to examine the effect of problem difficulty (with or without carrying in solution) on ERPs. After the presentation of the second addend, N1, P1, N2, late positive complex and slow waves were recorded. The P2 amplitude at F3 site for the difficult arithmetic problems between 168 and 184 ms is larger (more positive) than that for easy problems (P < 0.05). The mean latency of P2 at F7 and P3b at F3 and F4 is significantly longer for difficult problems than that for easy ones (P < 0.05). It is suggested that prefrontal activity may be involved in the arithmetic data retrieval process. ERPs is modified to different degrees by changing the difficulty of mental arithmetic.

Adult↗

Rhodobacter capsulatus DNA topoisomerase I purification and characterization.

A 30-kDa DNA topoisomerase has been purified to near homogeneity from the purple nonsulfur photosynthetic bacterium Rhodobacter capsulatus. The enzyme is recognized by an antibody against a 16-mer peptide sequence from human DNA topoisomerase I. The purified enzyme is a type I topoisomerase. Consistent with the properties of other prokaryotic type I DNA topoisomerases, the isolated enzyme is unable to relax positively supercoiled DNA and absolutely requires divalent cations for its relaxation activity. However, regardless of the Mg+2 concentrations, ATP concentrations above 5 mM completely inhibit the relaxing activity. The enzyme is sensitive to high salt concentrations and the optimal activity occurs at salt concentrations between 3 and 30 mM for monovalent cations. Single-stranded M13 DNA is a strong inhibitor of this relaxing activity. The enzyme is inhibited by ethidium bromide, confirming that this DNA topoisomerase is incapable of relaxing positive supercoils. Topoisomerase I-specific inhibitors like Hoechst 32258 and actinomycin D inhibit the enzymatic activity while the enzyme is resistant to type II topoisomerase inhibitors such as norfloxacin, nalidixic acid, and novobiocin. From these enzymatic characteristics, we conclude that the R. capsulatus DNA topoisomerase is a prokaryotic type I DNA topoisomerase.

Bacterial Proteins↗

Fast reversible electron transfer for photosynthetic reaction center from wild type Rhodobacter sphaeroides re-constituted in polycation sandwiched monolayer film.

Direct reversible electron transfer for photosynthetic reaction center from wild type Rhodobacter sphaeroides re-constituted in polycation sandwiched monolayer film was observed in this work. The redox potential E0' = 0.46 V vs. NHE for first primary donor redox couple P/P+ was accurately measured from reversible CV or SWV peaks, which were quite close to those obtained from optic redox titration method. Reaction center (RC) in film was found re-constituted in such an ordered way that the orientation of RC favored the electron transfer in film. Thus, the protein electroactivity seems to be turned on in this artificial biomimic thin film. Furthermore, RC in the film features a photo-induced redox-peak fluctuation, suggesting an intact and functional state for RC in such film. Redox peaks were also found dependent of pH, implying a proton-coupled electron transfer occurring in film. Charge recombination was observed accompanied with change of electrochemical driving force. Electrochemical model assuming several classes of electroactive sites in the films on the electrode with a dispersion of standard potentials successfully fits SWV experimental data at different pulse height and frequency.

Electrochemistry↗

Assembly of the alpha-globin mRNA stability complex reflects binary interaction between the pyrimidine-rich 3' untranslated region determinant and poly(C) binding protein alphaCP.

Globin mRNAs accumulate to 95% of total cellular mRNA during terminal erythroid differentiation, reflecting their extraordinary stability. The stability of human alpha-globin mRNA is paralleled by formation of a sequence-specific RNA-protein (RNP) complex at a pyrimidine-rich site within its 3' untranslated region (3'UTR), the alpha-complex. The proteins of the alpha-complex are widely expressed. The alpha-complex or a closely related complex also assembles at pyrimidine-rich 3'UTR segments of other stable mRNAs. These data suggest that the alpha-complex may constitute a general determinant of mRNA stability. One or more alphaCPs, members of a family of hnRNP K-homology domain poly(C) binding proteins, are essential constituents of the alpha-complex. The ability of alphaCPs to homodimerize and their reported association with additional RNA binding proteins such as AU-rich binding factor 1 (AUF1) and hnRNP K have suggested that the alpha-complex is a multisubunit structure. In the present study, we have addressed the composition of the alpha-complex. An RNA titration recruitment assay revealed that alphaCPs were quantitatively incorporated into the alpha-complex in the absence of associated AUF1 and hnRNP K. A high-affinity direct interaction between each of the three major alphaCP isoforms and the alpha-globin 3'UTR was detected, suggesting that each of these proteins might be sufficient for alpha-complex assembly. This sufficiency was further supported by the sequence-specific binding of recombinant alphaCPs to a spectrum of RNA targets. Finally, density sedimentation analysis demonstrated that the alpha-complex could accommodate only a single alphaCP. These data established that a single alphaCP molecule binds directly to the alpha-globin 3'UTR, resulting in a simple binary structure for the alpha-complex.

3' Untranslated Regions↗

Expression of membrane-associated macrophage colony-stimulating factor (M-CSF) in Hodgkin's disease and other hematologic malignancies.

We have identified a membrane-bound form of M-CSF (m-M-CSF) from an established human leukemic J6-1 cell line. To further understand its biological significance, we studied the expression of this membrane-associated growth factor in the lymph nodes of lymphoma patients and bone marrow smears from patients with hematologic diseases by immunohistochemical staining using anti-M-CSF MAb. We detected a high incidence of m-M-CSF expression in 75% (9/12) of the lymph node sections from patients with Hodgkin's Disease (HD). The antigens were detected primarily in large clusters of mononuclear Hodgkin's cells and the extracellular matrix (EM) surrounding them. In one HD patient with abundant multinucleated Reed-Sternberg (R-S) cells, all of them were intensely stained with anti-M-CSF MAb. In non-Hodgkin's lymphomas (NHL), the incidence (17.6 %) of m-M-CSF expression was lower (3/17). Yet, no m-M-CSF antigens were detected in the lymph nodes from six cases of non-hematologic malignancies and other diseases. A high response also was detected in bone marrow smears obtained from patients with hematologic malignancies, which include myeloid leukemias (32.5%), lymphomas with bone marrow metastasis (50%) and myelodysplastic syndromes (MDS) (37.5 %). By comparison, only 6.8 % of bone marrow smears from non-malignant hematologic diseases and 2.7% of lymphoid leukemias showed positive staining with anti-M-CSF MAb. Our results showed that high expression of m-M-CSF antigens is linked to some types of lymphomas, especially HD. and myeloid leukemias, and may play a role in the development of these hematologic malignancies.

Adult↗

A claims data approach to defining an episode of care.

OBJECTIVE: To utilize health services research techniques in developing an episode of care using an administrative data set. This method is demonstrated for an episodic clinical condition, migraine. DATA SOURCES: Medicaid administrative data set of 3,372 patients with a diagnosis of migraine (ICD-9-CM 346.0, 346.1) in the state of Pennsylvania between May 1990 and March 1992. STUDY DESIGN: The duration of a migraine episode was measured by assessing the magnitude of resource utilization and the proportion of patients with charges in the period after the index migraine as compared to the period before the index migraine. A confidence interval (CI) was developed around each measure using bootstrap techniques. DATA COLLECTION METHODS: All charge data were extracted daily for a 113-day observation period surrounding each index migraine in order to observe the duration of impact of a migraine diagnosis on resource utilization. PRINCIPAL FINDINGS: The lower limits of both the 95% and 99% CIs for the difference in charges are greater than 0 for three weeks. The lower limits of both CIs for the difference in the proportion of patients with charges are above 0 for six weeks. CONCLUSIONS: Our analysis demonstrates that a health services research framework can be used to define an episode of care for a chronic disease category such as migraine. This method can be used to evaluate episodes of care for clinical studies of limited or episodic conditions and to complement clinical expertise in developing time horizons for clinical trials.

Adult↗

Astrocytes interact intimately with degenerating motor neurons in mouse amyotrophic lateral sclerosis (ALS).

Astrocytic proliferation and hypertrophy (astrogliosis) are associated with neuronal injury. However, neither the temporal nor the spatial relationship between astrocytes and injured neurons is clear, especially in neurodegenerative diseases. We investigated these questions in a mouse amyotrophic lateral sclerosis (ALS) model. The initial increase in astrogliosis coincided with the onset of clinical disease and massive mitochondrial vacuolation in motor neurons. After disease onset, astrogliosis increased further in parallel with the number of degenerating motor neurons. Examination of individual astrocytes by three-dimensional reconstruction revealed that astrocytes extended their processes toward, wrapped around, and sometimes penetrated vacuoles derived from neuronal mitochondria. These results show a close temporal correlation between the onset of neuronal degeneration and the beginning of astrogliosis in this neurodegenerative disease and reveal a novel spatial relationship that is consistent with the view that astrocytes play an active role in the neuronal degeneration process.

Amyotrophic Lateral Sclerosis↗

Different systems in human brain are involved in presemantic discrimination of pictures as revealed by event-related potentials.

It is uncertain if the several brain areas in response to presemantic picture processing are functionally homogeneous. Subjects were asked to discriminate visual stimulus pairs and event-related potentials (ERPs) were recorded from the scalp. A line-drawing picture (S1) was followed by another stimulus (S2) 600 ms later. S2 was the same as S1 in condition 1, a reversed picture of S1 in condition 2, the corresponding Chinese word in condition 3 and the syllabic alphabet of S1 in condition 4. Amplitudes of ERPs over right posterior scalp with time window from 102-180 ms after the onset of S2 in condition 1 and 2 were significantly larger than condition 3 and 4. The N2 component on the right anterolateral scalp with time window from 182-240 ms was significantly larger in condition 1 than other conditions, whereas the N2 on the left anterolateral scalp with time window from 262-350 ms in condition 2, 3 and 4 was significantly larger than condition 1. It is suggested that pictures and words are processed in different systems at the presemantic stage: repetitive and physically deviant stimuli evoke different responses in different brain regions.

Adult↗

Massive mitochondrial degeneration in motor neurons triggers the onset of amyotrophic lateral sclerosis in mice expressing a mutant SOD1.

Amyotrophic lateral sclerosis (ALS) involves motor neuron degeneration, skeletal muscle atrophy, paralysis, and death. Mutations in Cu,Zn superoxide dismutase (SOD1) are one cause of the disease. Mice transgenic for mutated SOD1 develop symptoms and pathology similar to those in human ALS. To understand the disease mechanism, we developed a simple behavioral assay for disease progression in mice. Using this assay, we defined four stages of the disease in mice expressing G93A mutant SOD1. By studying mice with defined disease stages, we tied several pathological features into a coherent sequence of events leading to motor neuron death. We show that onset of the disease involves a sharp decline of muscle strength and a transient explosive increase in vacuoles derived from degenerating mitochondria, but little motor neuron death. Most motor neurons do not die until the terminal stage, approximately 9 weeks after disease onset. These results indicate that mutant SOD1 toxicity is mediated by damage to mitochondria in motor neurons, and this damage triggers the functional decline of motor neurons and the clinical onset of ALS. The absence of massive motor neuron death at the early stages of the disease indicates that the majority of motor neurons could be rescued after clinical diagnosis.

Amyotrophic Lateral Sclerosis↗