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Biomedical subjects

J S Han

Publications and source records attributed to J S Han.

At least 55 records · Page 3Linked to original sources

Diffuse alveolar hemorrhage in lupus nephritis.

AIM: Diffuse alveolar hemorrhage (DAH) is a rare and catastrophic event in systemic lupus erythematosus (SLE) with a high mortality rate, and little information is available about the degree of renal involvement in this condition. PATIENTS AND METHODS: To evaluate the effects of renal impairment on the course of DAH, the hospital records of 7 patients (9 episodes) with DAH and SLE between 1988 and 1998 at Seoul National University Hospital were reviewed. A diagnosis of DAH was established when the patient had an acute pulmonary syndrome including either hemoptysis, new alveolar infiltrates on the chest radiograph, the presence of a falling hematocrit or hemorrhagic BAL. All patients were women and their median age was 26 years ranging between 23 and 39. All patients had concurrent lupus nephritis and 4 of them were classified as WHO class IV with renal pathology. RESULTS: Their median serum creatinine level at the time of DAH was 4.6 mg/dl (0.8 - 13.6), and the median daily proteinuria amount was 778 mg (436 - 6200). All of the patients received corticosteroid therapy, and intravenous cyclophosphamide was given to 3 cases. Hemodialysis was done in 3 cases, and 4 of the 7 patients died during an acute event. We reviewed five series about the clinical parameters, including the serum creatinine level, treatment and hospital outcome. From the results of the analysis, it was determined that concomitant infection (RR 4.2) and the use of mechanical ventilation (RR 6.1) were associated with the increased risk of mortality, but azotemia (sCr > 3.0 mg/dl) (RR 1.5) or hemodialysis therapy (RR 1.3) was not shown to have a significant association. CONCLUSION: It could be suggested that even though renal failure is combined with DAH in SLE patients, the same aggressive treatment results in a comparable outcome as patients with normal renal function.

Acute Disease↗

Clinical significance of the fractional excretion of anions in metabolic acidosis.

The fractional excretion of anions has been proposed as a new index for the differential diagnosis of metabolic acidosis, identifying the properties of the conjugate base by examining the renal handling of the anion. Here, we investigated clinical significance of the fractional excretion of anions in pathophysiologic diagnosis of metabolic acidosis by measuring urine ammonium (NH4+) excretion, the ratio of A plasma anion gap/delta plasma HCO3- concentration (deltaAG/deltaHCO3-), and fractional excretion of anions in three different groups of metabolic acidosis: acid overproduction (8 patients with lactic acidosis, 8 with diabetic ketoacidosis, 3 with hippuric acidosis following glue sniffing), acid underexcretion (10 patients with chronic renal failure) and normal controls (10 normal volunteers who underwent 3-day NH4Cl loading). As expected, urine NH4+ excretion was higher in overproduction acidosis than in acid-loaded normal controls (88.1 +/- 12.3 vs. 54.0 +/- 3.7 mmol/day, p < 0.05), and it was lower in chronic renal failure than in acid-loaded normal controls (12.8 +/- 1.7 vs. 54.0 +/- 3.7 mmol/day, p < 0.05). The fractional excretion of anions had no difference between overproduction acidosis and chronic renal failure (41.2 +/- 42.8% vs. 41.0 +/- 8.1%). However, the fractional excretion of anions showed significant differences between the subgroups in acid overproduction (lactic acidosis, 4.7 +/- 0.3%; diabetic ketoacidosis, 45.8 +/- 3.1%; hippuric acidosis, 126.0 +/- 14.4%; p < 0.05). The ratio of plasma deltaAG/deltaHCO3- also exhibited significant differences between the subgroups in acid overproduction (lactic acidosis, 1.5 +/- 0.1; diabetic ketoacidosis, 1.0 +/- 0.1; hippuric acidosis, 0.3 +/- 0.1; p < 0.05). There was an inverse linear correlation between the fractional excretion of anions and the ratio of plasma deltaAG/deltaHCO3- (r2 =-0.89, p < 0.05). In conclusion, determination of the fractional excretion of anions may provide a useful clue to the differential diagnosis of metabolic acidosis caused by acid overproduction.

Acidosis↗

[Frequency-specific responses of human brain to peripheral transcutaneous electric nerve stimulation: a functional magnetic resonance imaging study].

The purpose of the present investigation was to determine the responses of human brain to transcutaneous electric nerve stimulation (TENS) at different frequencies by functional magnetic resonance imaging (fMRI) examinations covering the whole brain of eleven healthy volunteers. Each subject received TENS at acupoints ST36 and SP6 of the left leg at the frequencies of 2 and 100 Hz. Frequency-specific responses were found in motor-related areas, thalamus, limbic system and associated cortex to stimulation of the two frequencies, while the primary somatosensory areas were activated by both. Therefore, it appears that 2 and 100 Hz TENS act through different neuro-pathways in the central nervous system.

Acupuncture↗

[Progress in the study of pain by brain imaging].

This review deals with the recent functional brain imaging studies of pain. In summary, the sensory-discriminative component of pain is related with the lateral thalamus, primary and secondary somatosensory area and insular cortices, while the posterior parietal and prefrontal cortices seem to play a role in the cognitive-attentional process of nociceptive information. Different parts of anterior cingulate gyrus are correlated with cognitive and emotional aspects of pain. Brain imaging data obtained from clinical patients suffering from various kinds of pain especially neuropathic pain, were discussed at the end of this article.

Animals↗

Role of hippocalcin in Ca2+ -induced activation of phospholipase D.

The role of hippocalcin as a novel mediator in the PKC-independent Ca2+ -induced phospholipase D (PLD) activation pathway was investigated. Hippocalcin was expressed in the Sf9 insect cell expression system because the myristoylation of this protein is essential for its function. PLD and Cdc42 proteins were prepared from a rat brain cell membrane and cytosol, respectively. The recombinant hippocalcin was expressed in the Sf9 cell using expression vector pVL1393. The hippocalcin expressed was purified as a single band on PAGE following the hydrophobic phenyl HPLC and TSKgel G3000SW gel filtration HPLC. The molecular size of the rat brain hippocalcin expressed in this system was estimated to be 22 kDa. Myristoylated hippocalcin migrated faster than the non-myristoylated form on SDS-PAGE. Less than 10% of the total hippocalcin expressed was myristoylated in this baculovirus expression system. PLD was extracted from rat brain membranes and chromatographically enriched 70-fold. From the rat brain cytosol, Cdc42 was purified to near homogeneity. While hippocalcin alone did not activate PLD, it increased PLD activity activated with Cdc42 1.8-fold in the presence of calcium (300 nM free calcium). In the absence of calcium in the reaction mixture, the effect of hippocalcin to facilitate Cdc42-activated PLD activity was abolished. This result suggests that hippocalcin might be one of the regulatory proteins in the PKC-independent Ca2+ -mediated PLD activation pathway in conjunction with the Cdc42 protein.

Animals↗

Analysis of trimethylsilyl derivatization products of phosphatidylethanol by gas chromatography-mass spectrometry.

For the detection of rare phospholipid, phosphatidylethanol (PEt), GC-MS analysis method was adopted for the detection of derivatization products of PEt by N,O-bis (trimethylsilyl) trifluroacetamide (BSTFA). A re-structured molecule derived from PEt, ethyl bis (trimethylsilyl)-phosphate was found from search of Wiley database. This molecule can be used as a marker for PEt analysis. The molecular formula was C8H23O4PSi2 and weight of the formula was 270.09.

Gas Chromatography-Mass Spectrometry↗

The arc two-component signal transduction system inhibits in vitro Escherichia coli chromosomal initiation.

Under anaerobic growth conditions, Escherichia coli operates a two-component signal transduction system, termed Arc, that consists of ArcB protein, a transmembrane sensor kinase and ArcA protein, the cognate response regulator. In response to low oxygen levels, autophosphorylated ArcB phosphorylates ArcA, and the resulting phosphorylated ArcA (ArcA-P) functions as a transcriptional regulator of the genes necessary to maintain anaerobic growth. Under anaerobic conditions, cells maintain a slow growth rate, suggesting that the initiation of chromosomal replication is regulated to reduce the initiation frequency. DNase I footprinting experiments revealed that ArcA-P binds to the left region of the chromosomal origin, oriC. ArcA-P did not affect the in vitro replication of plasmid DNA containing the ColE1 origin nor the in vitro replication of viral DNAs; however, ArcA-P specifically inhibited in vitro E. coli chromosomal replication. This inhibition was caused by the prevention of open complex formation, a necessary step in the initiation of chromosomal replication. Our in vitro results suggest that the Arc two-component system participates in regulating chromosomal initiation under anaerobic growth conditions.

Bacterial Outer Membrane Proteins↗

Overexpression of phospholipase D1 in human breast cancer tissues.

Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine (PC) to produce phosphatidic acid (PA) and choline. PLD is a major enzyme implicated in important cellular processes, such as cell proliferation. We designed this study to investigate the expression of PLD in human breast carcinomas and non-malignant tissues using RT-PCR, Western blot analysis, immunohistochemistry and an Arf-dependent PLD activity assay. We examined about 550 bp of PCR product and 120 kDa of PLD protein. Our results showed that PLD protein and mRNA levels were overexpressed in 14 of 17 breast cancer tissues. We also observed increased expression by immunohistochemistry and Arf-dependent PLD activity in microsomes of human breast tumors, which correlated well with PLD expression. PLD expression was elevated in human breast tumors compared with normal breast tissues. These results implicate a possible role of PLD in human breast tumorigenesis and suggest that PLD may be useful as a marker for malignant disease in the breast.

ADP-Ribosylation Factors↗

Spinal kappa-opioid system plays an important role in suppressing morphine withdrawal syndrome in the rat.

To explore the possible involvement of spinal kappa-opioid receptor in modulating morphine withdrawal syndrome, rats were made dependent on morphine by multiple injections of morphine HCl for 5 days. They were then given intrathecal administration (i.t.) of a kappa-opioid receptor agonist trans-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzenacetamide hydrochloride (U-50,488H, 2.5-10 microg) or its antagonist nor-binaltorphimine (nor-BNI, 1.25-5 microg), followed by intraperitoneal administration (i.p.) of naloxone (0.5 mg/kg), and the withdrawal syndrome was scored for 60 min. U-50,488H produced a dose-dependent suppression, whereas nor-BNI a dose-dependent potentiation in withdrawal syndrome. The latter result implies that an endogenous kappa receptor agonist, most probably dynorphin, exerts a tonic suppressive effect on morphine syndrome at spinal level.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Endomorphin and mu-opioid receptors in mouse brain mediate the analgesic effect induced by 2 Hz but not 100 Hz electroacupuncture stimulation.

This work was designed to examine whether brain endomorphins (EM1 and EM2), the endogenous mu-opioid ligands, are involved in electroacupuncture (EA)-induced analgesia in the mice. C57BL/6J mice were given EA for 30 min and the effect of EA-induced analgesia was assessed by radiant heat tail flick latency (TFL). Intracerebroventricular (i.c.v.) injection of mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Tyr-Orn-Thr-Pen-Thr-NH(2) (CTOP), or antiserum against EM1 or EM2 was performed to see whether EA analgesia could be blocked. The results showed that: (1) i.c.v. injection of CTOP at 25-100 ng dose-dependently antagonized the analgesia induced by EA of 2 Hz, but not 100 Hz. (2) Intracerebroventricular injection of EM1 antiserum (5 ml, 1:1 or 1:10 dilution) dose-dependently antagonized 2 Hz, but not 100 Hz EA analgesia. (3) EM2 antiserum showed similar effect at 1:1 dilution. The results are interpreted to mean that endogenously released EM1 and EM2 and the cerebral mu-receptors are involved in mediating 2 Hz but not 100 Hz EA analgesia in the mice.

Animals↗

Molecular cloning and sequencing of rat Cdc42 GTPase cDNA.

Cdc42 is a member of the Rho family of small GTP-ase and plays an important role in intracellular signaling pathways regulating cell morphology, motility and stimulation of DNA synthesis. We have isolated cDNA encoding Cdc42 from a rat brain cDNA library using PCR-cloning strategy. The sequence of isolated gene revealed an open reading frame of 576 nucleotides with the potential to encode a protein of 191 amino acids with a predicted molecular weight of 21 kD. The resulting sequence was incorporated into the GenBank with accession number, AF205635. Sequence analysis revealed that overall cDNA sequence identity is 96% with human G25K and 52% with rat Chp, a homologue of the GTPase human Cdc42Hs, and having one nucleotide difference from the mouse Cdc42. However, putative protein sequence was identical to the mouse and human brain Cdc42Hs. On expression of the cDNA in COS-7 cells, a protein molecular weight of 21 kD was detected in immunoblotting using anti-human Cdc42 antibodies. Therefore, these results suggest that the cDNA we are reporting is most likely the rat homologue of the GTPase human Cdc42.

Amino Acid Sequence↗

Lesions of the amygdala central nucleus alter performance on a selective attention task.

Previous studies showed a role for the amygdala central nucleus (CN) in attentional processing during the acquisition of Pavlovian associations. Both the acquisition of conditioned orienting responses and the surprise-induced enhancement in the ability of conditioned stimuli to enter into new associations depend on the integrity of CN. In this experiment, the role of CN in the performance of a well-learned selective attention task was examined. Rats with ibotenic acid lesions of CN and control rats first learned a discrete-trial, multiple-choice reaction time task. On each trial, after a constant-duration ready signal, the rats were required to poke their noses into one of three ports, guided by the brief illumination of one of those ports. Rats with CN lesions were slower to acquire the task than control rats but showed equivalent asymptotic sustained performance. Subsequent attentional challenges, which included reducing the duration of the port illumination and varying the duration of the ready signal, had greater impact on the performance of lesioned than control rats. These data resemble those reported from similar tasks after damage to the basal forebrain (BF) system. Together with earlier findings, these data support a role for CN in modulating visuospatial attention in action as well as in the acquisition of associations, perhaps by way of its projections to BF cholinergic systems.

Amygdala↗

Stress or drug priming induces reinstatement of extinguished conditioned place preference.

To construct a model for the relapse of drug use, we investigated the reinstatement of morphine-induced conditioned place preference (CPP) in rats. After the morphine CPP paradigm was established, rats were left extinguishing for 9 days, then exposed to 15 min of random foot shock or s.c. drug priming with different doses of morphine or amphetamine, respectively. Foot shock or a higher dose (0.25 mg/kg) of both drugs could reinstate the CPP induced by 4 mg/kg of morphine after a 9-day extinction, while a lower dose (0.125 mg/kg) of both drugs had no effect. It is concluded that the CPP extinction-reinstatement paradigm might be used as a model to investigate the mechanism of relapse in addicts.

Amphetamine↗

Pattern of deposition of stainless steel welding fume particles inhaled into the respiratory systems of Sprague-Dawley rats exposed to a novel welding fume generating system.

In order to investigate occupational diseases related to welding fume exposure, such as nasal septum perforation, pneumoconiosis and manganese intoxication, we built a welding fume exposure system that included a welding fume generator, exposure chamber and fume collector. The fume concentrations in the exposure chamber were monitored every 15 min during a 2-h exposure. Fume (mg/m(3)) concentrations of major metals, including Fe, Mn, Cr, and Ni were found to be consistently maintained. An acute inhalation toxicity study was conducted by exposing male Sprague-Dawley rats to the welding fumes generated in this apparatus by stainless steel arc welding. The rats were exposed in the inhalation chamber to a welding fume with a concentration of 62 mg/m(3) total suspended particulates for 4 h. Animals were sacrificed at 4 h and at 1, 3, 7, 10, and 14 days after exposure. Histopathological examinations were conducted on the animals' upper respiratory tracts, including the nasal pathway and the conducting airway, and on the gas exchange region including the alveolar ducts, alveolar sacs, and alveoli. Diameters of fume particles varied from 0.02 to 0.81 microm and were distributed log normally, with a mean diameter of 0.1 microm and geometric standard deviation of 1.42. Rats exposed to the welding fume for 4 h did not show any significant respiratory system toxicity. The mean particle diameter of 0.1 microm resulted in little adsorption of the welding fume particles in the upper respiratory tract. Particle adsorption took place principally in the lower respiratory tracts, including bronchioles, alveolar ducts, alveolar sacs, and alveoli.

Administration, Inhalation↗

Temperature and salt effects on proteolytic function of turnip mosaic potyvirus nuclear inclusion protein a exhibiting a low-temperature optimum activity.

The nuclear inclusion protein a (NIa) of turnip mosaic potyvirus is a protease responsible for processing the viral polyprotein into functional proteins. The NIa protease exhibits an unusual optimum proteolytic activity at about 16 degrees C. In order to understand the origin of the low-temperature optimum activity, the effects of temperature and salt ions on the catalytic activity and the structure of the NIa protease have been investigated. The analysis of the temperature dependence of k(cat) and K(m) revealed that K(m) decreases more drastically than k(cat) as temperature decreases. The thermodynamic analysis showed that the decrease of K(m) is driven entropically, suggesting a possibility that the substrate binding might need a large entropy cost. The secondary structure of the NIa protease was significantly perturbed at temperatures between 20 and 40 degrees C and the protease was unfolded at very low concentrations of guanidine hydrochloride with a transition midpoint of 0.8 M. These results suggest that the NIa protease is highly flexible in structure. Interestingly, salt ions including NaCl, KCl, CaCl(2) and MgCl(2) stimulated the proteolytic activity by 2-6-fold and increased the optimum temperature to 20-25 degrees C. This stimulatory effect of the salt ions was due to the lowering of K(m). The salt ions promoted the structural rigidity as evidenced in the higher resistance to the heat-induced unfolding in the presence of the salt ions. The increase in rigidity may lead to the lowering of K(m) possibly by reducing the entropic cost for substrate binding. Taken together, these results suggest that the NIa protease is highly flexible in structure and the low-temperature optimum activity might possibly be attributed to lowered entropy cost for substrate binding at lower temperatures.

Catalysis↗

Major house dust mite allergen, Der p I, activates phospholipase D in human peripheral blood mononuclear cells from allergic patients: involvement of protein kinase C.

The major house-dust-mite allergen, Der p I, stimulates the phospholipase D (PLD) in peripheral blood mononuclear cells (PBMC) from allergic patients with maximal responses after 30 min exposure. At 30 min, Der p I stimulated PLD activity by 1.4-fold in mild, 1.6-fold in moderate and 2-fold in severe allergic patients over control values (p < 0.05). When the cells were pretreated for 24 h with phorbol myristate acetate to down-regulate protein kinase C (PKC), PLD stimulation by Der p I was largely abolished. These results indicate that in PBMC from allergic patients, Der p I can stimulate PLD activity, and that PKC activation is involved in this stimulation.

Adult↗

Repeated administration of low dose ketamine for the treatment of monoarthritic pain in the rat.

The aim of the present study was to observe the effect of repeated subcutaneous (sc) injections of low doses of ketamine for the treatment of acute inflammatory pain in a complete Freund's adjuvant-induced monoarthritic pain model in rats. The results show: (1) sc injection of ketamine at a dose of 2 mg x kg(-1) or 10 mg x kg(-1) produced significant analgesia (P<0.01) in arthritic rats starting from the 2nd week and 3rd week, respectively. (2) Repeated administration of ketamine produced a significant reduction of the circumference of the arthritic ankle (P<0.05 and P<0.01 with different doses). (3) The body weight of the rats was not affected by continuous administration of ketamine for 4 weeks. No abnormal locomotor behavior was observed (It was concerned but not systemically evaluated in this study). The results suggest that repeated sc injection of ketamine for 4 weeks significantly reduce inflammatory pain in monoarthritis without notable aversive side effects.

Analgesics↗