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Biomedical subjects

Y Kim

Publications and source records attributed to Y Kim.

At least 559 records · Page 31Linked to original sources

Effects of platelet-activating factor (PAF) receptor blockage on mucous glycoprotein secretion in cultured chinchilla middle ear epithelium.

Platelet-activating factor (PAF) is a naturally occurring phospholipid that acts as a pleiotropic mediator of inflammation via specific membrane receptors. It has been demonstrated in recent years that PAF is a strong secretagogue of mucous glycoprotein (MGP) in airways and middle ear epithelium. MGP secretion accompanies otitis media with effusion (OME) and prolongs the course of this disease by increasing the viscoelasticity of the fluid. It is important, therefore, to inhibit the pathological secretion of MGP in the treatment of otitis media. In the current study, we investigated the effects of PAF receptor inhibitor WEB 2170 BS on in vitro MGP secretion. At concentrations of 100 mu M, PAF significantly stimulated MGP secretion. WEB 2170 BS significantly inhibited this PAF-simulated MGP secretion at concentrations of 2000 mu M. The action of WEB 2170 BS was concentration-dependent. However, it did not affect MGP secretion stimulated by IL-1beta, suggesting that WEB 2170 BS inhibits PAF-stimulated MGP secretion, specifically. It was noted that WEB 2170 BS did not completely eliminate MGP secretion induced by PAF even though a high concentration was used. The fact that WEB 2170 BS alone does not exhibit an inhibitory or stimulatory effect on the secretion of MGP suggests that WEB 2170 BS competitively binds to PAF receptors and possesses less affinity to PAF receptors than PAF.

Animals↗

Effect of matrix glycation on expression of type IV collagen, MMP-2, MMP-9 and TIMP-1 by human mesangial cells.

Human mesangial cells grown in either 5 or 25 mM glucose were cultured on type IV collagen which had been previously control-incubated or in vitro glycated. Northern blot analysis revealed that after 3-7 days in culture mesangial cells on glycated type IV collagen expressed approximately 25-200% more alpha 1 (IV), approximately 20-50% less matrix metalloproteinase 2 (MMP-2), and 65-75% more tissue inhibitor of metalloproteinase 1 (TIMP-1). Decreased immunoreactivity (approximately 30-40%) and collagenolytic activity (approximately 10-40%) corresponding to MMP-2 was also detected in media conditioned during the third day of culture on glycated type IV collagen. These effects on cell function were related to the extent of type IV collagen modification and were similar for cells cultured in 5 or 25mM glucose. Elevated glucose (25 vrs 5 mM) increased expression of alpha 1 (IV) mRNA (approximately 40-70%) and in conjunction with matrix glycation resulted in detectable levels of MMP-9 message by northern blot although collagenolytic activity corresponding to MMP-9 was not detectable by zymography. We conclude that glucose and matrix glycation may each alter mesangial cell function, perhaps leading to an imbalance in mesangial matrix synthesis and degradation which could contribute to mesangial expansion characteristic of diabetic renal disease.

Blotting, Northern↗

Hematopoietic and reproductive hazards of Korean electronic workers exposed to solvents containing 2-bromopropane.

OBJECTIVES: The purpose of this study was to describe hematopoietic and reproductive hazards of Korean electronic workers exposed to solvents containing 2-bromopropane. METHODS: Detailed medical and occupational histories were taken and thorough physical examinations with clinical laboratory tests were done for 33 workers (8 men and 25 women). Previous and present exposure was investigated in detail by industrial hygienists. RESULTS: Of the 25 female workers, 16 were shown to have secondary amenorrhea with high follicle-stimulating hormone levels, normal prolactin levels, and hot flashes. A total of eight workers with amenorrhea concurrently showed findings of pancytopenia. Among eight male workers, two showed azoospermia and another four showed some degree of oligospermia (normal > 20 million. ml-1) or reduced sperm motility (normal > 50%). The bone marrow effects and the testis or ovarian failure was shown to be the main health hazards in this workplace. Except for the cleaning solution containing 97.4% 2-bromopropane, no other known physical or chemical agents could be identified as responsible for the gonadal and bone marrow effects, including ionizing radiation, lead, ethylene glycol ether and its acetates, benzene, and dibromochloropropane. CONCLUSIONS: No previous studies have reported human toxicity for 2-bromopropane, but the results of this study lead to the tentative conclusion that the causal agent for the gonadal and bone marrow effects among the workers might be 2-bromopropane.

Adult↗

The interaction between pindolol and epinephrine contained in local anesthetic solution to the left ventricular diastolic filling velocity in normal subjects.

To evaluate the interaction between the nonselective beta-blocker, pindolol, and epinephrine contained in a local anesthetic solution, the left ventricular diastolic filling velocity was examined with pulsed Doppler echocardiography. Arterial blood pressure (BP), the R-R interval on the electrocardiogram (RR), and Doppler echo-cardiographic measurements were recorded in seven healthy volunteers after 45 micrograms of epinephrine contained in lidocaine (L-E) was injected in the maxilla after pretreatment with 5 mg of pindolol. The administration of L-E caused the elevation of BP and an increase in RR interval. Peak early (E) and peak atrial (A) filling velocities decreased, whereas isovolumic relaxation time (IVRT) and diastolic filling period (DFP) were prolonged. Although the ratio of E to A (E/A) remained unchanged, E/A/DFP was reduced. In contrast, when L-E was given without pindolol pretreatment, RR interval was shortened and BP was unchanged. The increase of both E and A velocities and the shortening of both IVRT and DFP were observed. E/A remained unchanged but E/A/DFP was increased. These results suggested that L-E caused opposite effects on the left ventricular filling velocity in the presence or absence of pindolol. We conclude that epinephrine activates the left ventricular relaxation rate but impairs it in the presence of pindolol.

Adrenergic beta-Antagonists↗

Anesthetic considerations of two sisters with Beckwith-Wiedemann syndrome.

Anesthetic considerations of 21-mo-old and 4-yr-old sisters with Beckwith-Wiedemann syndrome during surgical repair of cleft palate and reduction of macroglossia are presented and discussed. This syndrome is characterized by exomphalos, macroglossia, gigantism, hypoglycemia in infancy, and many other clinical features. This syndrome is also known as exomphalos, macroglossia, and gigantism (EMG) syndrome. Principal problems associated with anesthetic management in this syndrome are hypoglycemia and macroglossia. Careful intraoperative plasma glucose monitoring is particularly important to prevent the neurologic sequelae of unrecognized hypoglycemia. It is expected that airway management would be complicated by the macroglossia, which might cause difficult bag/mask ventilation and endotracheal intubation following the induction of anesthesia and muscle paralysis, so preparations for airway difficulty (e.g., awake vocal cord inspection) should be considered before induction. A nasopharyngeal airway is useful in relieving postoperative airway obstruction.

Airway Obstruction↗

Integrin-mediated interactions between primary/T-sv40 immortalized human glomerular epithelial cells and type IV collagen.

The use of human glomerular epithelial cells (HGEC) in research has been severely restricted by several obstacles, which have been circumvented by the generation of T-SV40 immortalized human visceral glomerular epithelial cells (Delarue et al, 1991). In this work, we compared the primary and immortalized HGEC for expression of integrin and some nonintegrin surface receptors. We also studied the adhesion of both types of HGEC to glomerular basement membrane (GBM), type IV collagen (tIV), and its major noncollagenous NC1 domain. The integrins mediating adhesion of HGEC to tIV were also examined. Expression of integrin and some nonintegrin cell surface receptors was analyzed by flow cytometry. Adhesion to GBM, tIV, and its major noncollagenous NC1 domain was studied by direct solid phase cell adhesion assays. Identification of integrins mediating adhesion of HGEC to tIV was achieved by inhibition of cell adhesion using monoclonal antibodies to integrin subunits. The primary and immortalized HGEC share phenotypic characteristics, and alpha3beta1 appeared to be the major integrin present on both HGEC types. The kinetics of binding to GBM, tIV, and its noncollagenous NCI domain were similar in both the primary and immortalized HGEC, although the latter displayed a somewhat weaker binding. Both the primary and immortalized HGEC displayed significantly better adhesion to NC1-alpha3 compared with NC1-alpha1, alpha3beta1 appears to be the major integrin mediating the adhesion of HGEC to tIV. Our studies suggest that alpha3beta1 is the major integrin present on HGEC. This has been confirmed by flow cytometric analysis. In addition, we demonstrated a functional role for this integrin in mediating attachment of HGEC to tIV. Our data also demonstrate a preference in binding of HGEC to alpha3 chains of NC1 compared with alpha1 chains of NC1. These findings were seen in both the primary and immortalized HGEC. The T-SV40 immortalized HGEC can therefore serve as a very useful tool to study glomerular visceral cell biology.

Animals↗

Lovastatin inhibits lipopolysaccharide-induced NF-kappaB activation in human mesangial cells.

BACKGROUND: HMG-CoA reductase inhibitors have been shown to reduce glomerular injury in different models of progressive renal damage. The transcription factor NF-kappaB plays a major role in the induced expression of genes involved in cellular proliferation and inflammatory responses that could be important in the pathogenesis of glomerular injury. We therefore examined the effects of the HMG-CoA reductase inhibitor lovastatin on NFkappaB activation in human mesangial cells. METHODS: Cultured human mesangial cells were stimulated with bacterial lipopolysaccharide (LPS) in the presence or absence of lovastatin. NF-kappaB activity was measured by electrophoretic mobility shift assay (EMSA). RESULTS: LPS-stimulated mesangial cells exhibited an NF-kappaB-like activity as assessed by EMSA competition assays, and supershift assays with antibodies against the p50 and p65 subunits of NF-kappaB. Treatment of mesangial cells with lovstatin in the presence of exogenous cholesterol resulted in a significant reduction of the LPS-induced NF-kappaB activity. In the presence of either mevalonate or the mevalonate metabolite farnesyl pyrophosphate, the lovastatin inhibition of NF-kappaB activation was substantially reversed, supporting a role for mevalonate metabolites in LPS-induced mesangial cell NF-kappaB activation. CONCLUSIONS: These data suggest an additional mechanism by which HMG-CoA reductase inhibitors may reduce glomerular injury, namely, by inhibiting NF-kappaB activation and the subsequent proliferative and inflammatory responses.

Base Sequence↗

[Complex partial status epilepticus in a patient with a frontal cavernous angiomas].

We described a 34-year-old woman with a right frontal cavernous angioma who presented with complex partial status epilepticus (CPSE). In the first CPSE, complex partial seizure with complete unresponsiveness and tonic motor manifestation on her left arm occurred repeatedly at short intervals. Her consciousness was mildly disturbed between the seizures. An hour after the intra-venous administration of diazepam, her consciousness returned to normal. In the second CPSE, no motor manifestation was found, but complete unresponsiveness of short duration accompanied with stare and moderately impaired consciousness continued to occur. We emphasize the importance of not missing this rare non-convulsive epileptic status, especially when it does not present motor manifestations.

Adult↗

Severe perennial allergic rhinitis treated with Nd:YAG laser.

Allergic rhinitis is conventionally treated with anti-histamine or immunotherapy, although in many cases the results are unsatisfactory. Using a contact type Nd:YAG laser we have succeeded in relieving the symptoms of rhinitis by thermocoagulating only the inferior turbinate, making this a quick and effective form of treatment. The subjects were 60 patients with severe house-dust induced allergic rhinitis presented to the out-patient clinic of the ENT department of Nagoya City University Hospital. There were 25 men and 35 women ranging in age from 17 to 53 years. Patients were irradiated at an output of 10 W for 0.5 s for a total of about 386 joules for both nasal cavities. Prior to the procedure, surface anesthesia was applied using 10% cocaine. The irradiation was completed in only one out-patients session. The effects of this therapy were evaluated using 4 points to express the degree of subjective symptoms and intranasal findings. From one week before surgery the patient was asked to record symptoms (sneezing, blowing, blockage) every day, and to continue this recording until 4 weeks after surgery. After surgery no drugs were used. The effects were evaluated by adding up the total scores for sneezing, blowing, and blockage at one week intervals, and comparing the total scores between one week pre-operatively and those 1, 2, 3, and 4 weeks post-operatively. Full effect, including disappearance of symptoms, was obtained in 80%, good effect in 10%, fair effect in 5%, and no effect in 5%.

Adolescent↗

Clinical review of nasal allergy due to fungus.

In our clinic we have encountered nasal allergy due to fungi such as Candida, Aspergillus, and Alternaria. We therefore conducted a retrospective study of patients who consulted our Department between 1984 and 1991. A clinical review of patients who showed a positive skin test for Candida, Aspergillus, or Alternaria was performed. Our study revealed that Alternaria showed the highest ratio of strong positivity upon both RAST and skin test among the three fungi examined. These results led us to reconsider Alternaria as an important fungal antigen.

Adult↗

Adenine nucleotide metabolism of canine pancreas graft preserved by the two-layer (euro-collins' solution/perfluorochemical) method after reperfusion.

We have demonstrated that oxygenation of a pancreas during preservation by the two-layer method leads continued ATP production to maintain cellular integrity and produces an extended period of preserved pancreatic viability. In this study, we examined whether the pancreas grafts preserved by the two-layer method maintained adenine nucleotides pool as substrates for ATP synthesis before reperfusion and had the ability to synthesize ATP promptly and to recover energy charge potential (ECP) of the pancreas graft on reperfusion. After preservation by the two-layer cold storage method using EC for 48 hrs (group 1, n = 5), or simple cold storage in EC for 48 hrs (group 2, n = 5), canine pancreas grafts were autotransplanted. In control (group 3, n = 5), canine pancreas grafts were autotransplanted without preservation. Tissue adenine nucleotides concentrations were measured using high performance liquid chromatography (HPLC) before and after preservation, before reperfusion and after 1 hr- and 2 hr-reperfusion. Graft survival rates were 5/5, 0/5, and 5/5, in groups 1, 2 and 3, respectively. Total adenine nucleotides before reperfusion in group 1 was almost same levels as group 2 (7.41 +/- 1.47 vs 6.64 +/- 2.23 mumol/g dry weight, N.S.). Furthermore, ATP tissue levels in group 1 before reperfusion was 2.90 +/- 0.51 mumol/g dry weight and almost same levels as group 2 (2.03 +/- 0.68 mumol/g dry weight, N.S.). However, tissue ATP levels in group 1 after 2 hrs of reperfusion (6.71 +/- 1.19 mumol/g dry weight) were significantly higher than group 2 (4.51 +/- 0.51 mumol/g dry weight, P < 0.05), and almost same levels as control (group 3) (6.32 +/- 1.62 mumol/g dry weight, N.S.). In addition, ECP in group 1 and 3 (0.90 +/- 0.03 and 0.83 +/- 0.09, respectively) after 2 hr-reperfusion, were significantly higher than the value in group 2 (0.73 +/- 0.09, P < 0.01 and P < 0.05, respectively). It was clear that recovery of ATP on reperfusion was not depend on the residual nucleotides pool before reperfusion but the ability of the pancreas graft to recover tissue ATP levels and energy charge potential after reperfusion. We conclude that oxygenation of the pancreas graft during preservation by the two-layer method allows for ATP synthesis which is essential in maintaining cellular integrity and leads to maintain the graft's ability to recover ATP levels and energy charge potential promptly after reperfusion. Consequently the pancreas graft survives.

Adenine Nucleotides↗

Effects of C-1-substituted glucose analogue on the activation states of glycogen synthase and glycogen phosphorylase in rat hepatocytes.

A series of glucose-analogue inhibitors of glycogen phosphorylase b (GPb) has been designed, synthesized and investigated in crystallographic binding and kinetic studies. The aim is to produce a compound that may exert more effective control over glycogen metabolism than the parent glucose molecule and which could alleviate hyperglycaemia in Type-II diabetes. N-Acetyl-beta-D-glucopyranosylamine (1-GlcNAc) has a Ki for muscle GPb in crude extracts of 30 microM, 367-fold lower than that of beta-D-glucose [Board, Hadwen and Johnson (1995) Eur. J. Biochem. 228, 753-761]. In the current work, the effects of 1-GlcNAc on the activation states of GP and glycogen synthase (GS) in cell-free preparations and in isolated hepatocytes are reported. In gel-filtered extracts of liver, which lack ATP for kinase activity, 1-GlcNAc produced a rapid and time-dependent inactivation of GP with a subsequent activation of GS. Effects of 1-GlcNAc on both enzymes were stronger than those of glucose, with 0.8 mM 1-GlcNAc being equipotent with 50 mM glucose. At 1 mM, 1-GlcNAc enhanced the dephosphorylation of exogenous GPa by liver extracts (600%) and by muscle extracts (75%). This represents an approximately 500-fold improvement on glucose for the liver activity and 40-fold for the muscle activity. In whole hepatocytes, 1-GlcNAc showed an approximately 5-fold enhancement of glucose effects for GP inactivation but failed to elicit activation of GS. Glucose-induced activation of GS in whole hepatocytes was reversed by subsequent addition of 1-GlcNAc. However, when GS activation was achieved via the adenosine analogue and kinase inhibitor, 5'-iodotubercidin (ITU), subsequent addition of 1-GlcNAc allowed continued activation of GS. Phosphorylation of 1-GlcNAc in rat hepatocytes was established using radiolabelled material. The rate of phosphorylation was 1.60 nmol/min per 10(6) cells at 20 mM 1-GlcNAc but was reduced by the presence of 50 microM ITU (0.775 nmol/min per 10(6) cells). It is suggested that the phosphorylated derivative of 1-GlcNAc formed in hepatocytes is 1-GlcNAc 6-phosphate and that the presence of this species is responsible for the failure of 1-GlcNAc to activate GS. The relative importance of the reduction in concentration of GPa versus increased glucose 6-phosphate levels for activation of GS is discussed.

Acetylglucosamine↗

Crystallization and preliminary X-ray crystallographic analysis of DNA polymerase from Thermus aquaticus.

Two crystal forms of DNA polymerase from Thermus aquaticus have been grown at room temperature. Rhombohedral crystals (form I) grown from ammonium sulfate solution diffracted poorly to 10 A only and thus are not suitable for X-ray structure determination. Trigonal crystals (form II) grown from polyethylene glycol solution are more suitable for structure determination since their diffraction pattern extends to 2.5 A at cryogenic temperature upon exposure to synchrotron X-rays. They belong to space group P3(1)21 (or its enantiomorph P3(2)21) and their unit-cell dimensions are a = 106.7 and c = 169.7 A, for flash-frozen crystals. The presence of one molecule per asymmetric unit gives a crystal volume per protein mass (V(M)) of 3.0 A(3) Da(-l) and a solvent content of 58% by volume. X-ray data have been collected to 2.7 A Bragg spacing from native crystals.

Journal Article↗

Removal of phosphate from phosphohistidine in proteins.

Kinetic constants of KM = 0.8 microM, 3 microM and 1.6 microM, and kcat = 9 s-1, 7 s-1 or 9 s-1 were determined for histidine dephosphorylation by protein phosphatases 1, 2A and 2C respectively. IC50 values were determined for the inhibition of protein phosphatase 1 by inhibitor 1 (IC50 = 1 nM), inhibitor-2 (IC50 = 3 nM) and okadaic acid (IC50 = 30 nM) and for the inhibition of protein phosphatase 2A by okadaic acid (IC50 = 0.02 nM) and microcystin-LR (IC50 = 1 nM). Inhibitor-1 (Ki = 0.7 nM) and okadaic acid (Ki = 32 nM) are noncompetitive with protein phosphatase 1. Some of the IC50 values were low enough to violate the assumptions of the usual inhibition equations and a more general approach to the analysis of the data was used. On the basis of these kinetic parameters and the presence of phosphohistidine, the major cellular protein serine/threonine phosphatases are likely to act as protein histidine phosphatases in the cell.

Animals↗