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Biomedical subjects

H W Kim

Publications and source records attributed to H W Kim.

At least 73 records · Page 4Linked to original sources

Increased expression of Galphaq protein in the heart of streptozotocin-induced diabetic rats.

Heart disease is one of the major cause of death in diabetic patients, but the pathogenesis of diabetic cardio-myopathy remains unclear. In this experiment, to assess the significance of G protein signaling pathways in the pathogenesis of diabetic cardiomyopathy, we analyzed the expression of G proteins and the activities of second messenger dependent protein kinases: cAMP-dependent protein kinase (PKA), DAG-mediated protein kinase C (PKC), and calmodulin dependent protein kinase II (CaM kinase II) in the streptozotocin induced diabetic rat heart. The expression of Galphaq was increased by slightly over 10% (P<0.05) in diabetic rat heart, while Galphas, Galphai, and Gbeta remained unchanged. The PKA activity in the heart did not change significantly but increased by 27% (P<0.01) in the liver. Insulin treatment did not restore the increased activity in the liver. Total PKC activity in the heart was increased by 56% (P<0.01), and insulin treatment did not restore such increase. The CaM kinase II activity in the heart remained at the same level but was slightly increased in the liver (14% increase, P<0.05). These findings of increased expression of Galphaq in the streptozotocin-diabetic rat heart that are reflected by the increased level of PKC activity and insensitivity to insulin demonstrate that alteration of Galphaq may underlie, at least partly, the cardiac dysfunction that is associated with diabetes.

Animals↗

Identification of a type 6 protein ser/thr phosphatase regulated by interleukin-2 stimulation.

We have identified a 36 kD phosphoprotein that forms a complex with spliceosomal small nuclear ribonucleoproteins in lymphocyte extracts. This 36 kD protein is differentially phosphorylated in transformed human lymphoid cell lines and is regulated by IL-2 in peripheral blood T cells. We purified the 36 kD protein from human lymphocytes by employing a combination of immuno-affinity chromatography and preparative two-dimensional gel electrophoresis. Internal amino acid sequence analysis of the purified protein yielded two peptides that had perfect matches with sequences in the human protein serine/threonine phosphatase 6 (PP6). Using degenerate primers corresponding to the peptides, we obtained from a human T lymphocyte cDNA library a DNA fragment whose sequence is homologous to an EST cDNA clone (R05547). The predicted amino acid sequence of this clone showed over 98% sequence identity to human PP6. The identification of an IL-2 regulated type 6 protein serine/threonine phosphatase in lymphocytes was further substantiated by immunoblotting with anti-peptide antibodies. These findings suggest that PP6 is a component of a signaling pathway regulating cell cycle progression in response to IL-2 receptor stimulation.

Amino Acid Sequence↗

Prospective follow-up and pulmonary functions from a placebo-controlled randomized trial of ribavirin therapy in respiratory syncytial virus bronchiolitis. Ribavirin Study Group.

OBJECTIVE: To determine any long-term differences in adverse effects and pulmonary function between infants with respiratory syncytial virus and lower respiratory tract infection who were treated with ribavirin and a control group. STUDY DESIGN: Long-term follow-up included enumeration of episodes of respiratory illness, wheezing, and pneumonia and, ultimately, administration of pulmonary function tests (PFTs). Pulse oximetry was done at each visit. During the first 3 years we conducted follow-up in the fall and spring. In years 4 and 5 we conducted 1 visit per year. During years 5 through 7 we conducted PFTs, and starting with year 7 a methacholine chloride challenge was done if forced expiratory volume in 1 second (FEV1) was greater than 70% of predicted value. RESULTS: We prospectively enrolled (December 1983 to February 1985) in a randomized trial of ribavirin vs placebo children who were previously healthy, were premature, or had chronic pulmonary disease. One pulmonologist (R.F.; blinded) scored and interpreted the results of the PFTs. We studied 42 patients aged 1 to 33 months; 2 patients died (1 receiving ribavirin and 1 receiving placebo) and 5 patients receiving placebo were lost to follow-up; 35 patients (24 taking ribavirin and 11 taking placebo) attended 212 visits. Four patients were premature (3 in the ribavirin and 1 in the placebo group), and 3 of these had bronchopulmonary dysplasia (2 in the ribavirin and 1 in the placebo group). From years 1 to 3, there was more reactive airway disease, wheezing, and pneumonia in the placebo than in the ribavirin group (mean score, 22.3 for 12 placebo-treated patients vs. 15.8 for 23 ribavirin-treated patients; P = .07 by Kruskal-Wallis test); for all years, it was 22.0 for 11 placebo-treated patients vs. 16.0 for 22 ribavirin-treated patients (P = .10). After informed consent was given, 19 patients completed PFTs (13 receiving ribavirin and 6 receiving placebo); 7 of 13 ribavirin-treated patients (53%) had normal or mild PFT results vs. 0 of 6 placebo-treated patients (P = .04 by Fisher exact test). On methacholine challenge (7 ribavirin-treated patients and 5 placebo-treated patients), there was more reactivity in the placebo vs. the ribavirin group (exact P = .07). Scoring done by weighting for severity for 19 patients (13 ribavirin-treated patients and 6 placebo-treated patients) (even after correcting for asthma) showed a significant difference in favor of previously ribavirin-treated patients (exact P = .02). CONCLUSIONS: No outward effects were identified from ribavirin exposure. We observed no increase in reactive airway disease, wheezing, and pneumonia in the ribavirin compared with the placebo group. Weighted severity scores suggest long-term beneficial effect of ribavirin therapy; however, larger numbers should be evaluated.

Antiviral Agents↗

Spectral fitting of NMR spectra using an alternating optimization method with a priori knowledge.

As alternatives to the fast Fourier transform, advanced parametric methods based on the damped sinusoidal data model have been devised to better quantify the nuclear magnetic resonance (NMR) spectroscopy time-domain data. Previously, linear prediction (LP) fitting methods using Householder triangularization and singular value decomposition (SVD) techniques have been applied to the NMR spectroscopy data analysis. In this paper, we propose an alternating optimization method to quantify the time-domain NMR spectroscopy data. The proposed algorithm uses the a priori knowledge of the possible frequency intervals of the damped sinusoids to obtain more accurate parameter estimates when the NMR spectroscopy data are obtained under low signal-to-noise ratio conditions and the peaks are close together. None of the LP and SVD type of methods can use such approximate a priori knowledge. We have shown with measured NMR spectroscopy data that the proposed algorithm can be used to obtain accurate parameter estimates of frequencies, amplitudes, and damping ratios of the damped sinusoids and therefore the ultimate fit of the spectrum by using the a priori knowledge about the possible frequency intervals of the damped sinusoids.

Algorithms↗

Inhibitory effect of mast cell-mediated immediate-type allergic reactions by Cichorium intybus.

We investigated the effect of an aqueous extract of Cichorium intybus (CIAE) on mast cell-mediated immediate type allergic reactions. CIAE (0.1-1000 mg kg-1) dose-dependently inhibited systemic anaphylactic reaction induced by compound 48/80 in mice. Especially, CIAE inhibited compound 48/80-induced anaphylactic reaction 100% with the dose of 1000 mg kg-1. CIAE 1000 mg kg-1also significantly inhibited local anaphylactic reaction activated by anti-dinitrophenyl (DNP) IgE. When mice were pretreated with CIAE at a concentration ranging from 0.1 to 1000 mg kg-1, the plasma histamine levels were reduced in a dose-dependent manner. CIAE (1-1000 microg ml-1) dose-dependently inhibited histamine release from the rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cAMP in RPMC, when CIAE (1000 microg ml-1) was added, increased significantly compared with that of control cells. These results indicate that CIAE inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro.

Anaphylaxis↗

An efficient retrovirus-mediated transduction of human blood coagulation factor VIII cDNA in regenerating rat liver.

A retrovirus-mediated transduction of B-domain-deleted human blood coagulation factor VIII (FVIII-B) was attempted in partially hepatectomized rats. FVIII-B cDNA was inserted into a retroviral vector (pLNSX) and infective recombinant virus particles were produced in packaging cell lines (psi2 and PA317). Transfection of mouse NIH-3T3 cells with the FVIII-B cDNA inserted recombinant viruses, followed by G418 selection, gave a viral titer of 3.5 x 10(4) CFU/ml. FVIII-B protein, as well as FVIII-B mRNA, was detected in these cells. Transfusion of FVIII-B-expressing retrovirus particles into the tail vein of rats subjected to partial hepatectomy resulted in a relatively higher level of FVIII-B expression in liver and circulating plasma as compared with the sham-operated rats. These results indicate that the augmentation of FVIII activity in the blood of an animal by retroviral gene delivery can be enhanced by partial hepatectomy, and that the retrovirus-mediated FVIII-B cDNA delivery to regenerating liver may be an alternative method for the expression of FVIII-B cDNA in vivo.

3T3 Cells↗

Anterior cervical spinal epidural abscess in an infant.

Spinal epidural abscess (SEA) is rare in children, especially in newborns and infants, groups in which only very few cases have been reported. Because of the nonspecificity of presenting symptoms in children the diagnosis may be delayed, resulting in major permanent neurological deficits. In this paper, we report a case of cervical SEA in a 6-week-old infant who initially presented with fever and developed quadriparesis 19 days prior to admission. After emergency anterior decompression of the abscess the neurological function was improved immediately. Five months after surgery the neurological status was normal, an MR study showing disappearance of the epidural abscess and spinal cord indentation, and progressive fusion of the C3, C4 and C5 vertebral bodies. Anterior decompression without bone graft can provide an excellent prognosis in case of an anterior cervical SEA in infants.

Abscess↗

The prediction of interferon-alpha therapeutic effect by sequence variation of the HCV hypervariable region 1.

Interferon-alpha (IFN-alpha) has been used to treat hepatitis C virus (HCV)-induced hepatitis, but it has been effective in only about half of the treated patients, with recurrence appearing in the other half. As a consequence of the possible complications associated with IFN-alpha and the high cost of treatment, it has become extremely important to select the proper patients for IFN-alpha treatment. In our previous study, we found that the quasispecies in the hypervariable region (HVR) 1 of HCV were various and that a new quasispecies can appear in non-responders and/or lead to deterioration in the patients' condition. The preliminary data we obtained in the process of our previous research led us to believe that the quasispecies of HVR 1 has something to do with the effect of IFN-alpha. Thus, in this investigation, we tried to determine the predictive factors of IFN-alpha therapy. Thirty patients with HCV infection were treated with IFN-alpha. Among them, 15 patients recovered after six months IFN-alpha treatment, but the remaining 15 patients showed no response after six months IFN-alpha treatment. We cloned HVR 1 DNA by reverse transcription-polymerase chain reaction (RT-PCR) and examined the quasispecies of HVR 1. As the quasispecies of HVR 1 in non-responders varied more than in the complete remission group, we concluded that the sequence variation in HVR 1 of HCV can be used to predict the effect of IFN-alpha.

Adult↗

Effect of intermittent administration of parathyroid hormone on fracture healing in ovariectomized rats.

To evaluate the potential use as a therapeutic agent for osteoporotic fractures, we examined the effects of intermittent administration of parathyroid hormone on fracture healing in ovariectomized rats. At three months post-ovariectomy, bilateral tibial shaft fractures were induced and stabilized by intramedullary nailing with Kirschnerwires. Saline, 17-estradiol, or recombinant human PTH(1-84) was given once a day for 30 consecutive days during fracture healing. Fracture healing was assessed by morphometric and mechanical analysis of fracture callus. Intermittent parathyroid hormone administration increased the morphometric and mechanical parameters in a dose-dependent manner. 17-estradiol, a bone-resorption inhibiting agent, did not offer advantage in terms of fracture healing in ovariectomized rats. Our findings suggest that intermittent parathyroid hormone administration may benefit osteoporosis and fracture.

Animals↗

Behavior of CHO cells on phosphated cellulose membranes.

Phosphate groups (negatively charged chemical groups) were grafted onto the surface of cellulose membranes by a reaction between hydroxyl groups of cellulose and phosphorus pentoxide to observe the effect of phosphate groups on cellular behavior. X-ray photoelectron spectroscopy (XPS) was used to determine phosphorylation. Captive bubble contact angle measurement was used to determine surface wettability. XPS was also used to analyze serum protein adsorption. Chinese hamster ovary (CHO) cells were maintained in Ham's F-12 nutrient mixture with and without fetal calf serum. Total cell area and shape factor were analyzed using image-analyzing software. Serum proteins showed higher adsorption on phosphated cellulose. Cell spreading on phosphated membranes was greater than on the cellulose membrane that served as control. The cell growth rate was faster compared to the control. Large cell aggregates were not found on the phosphated membranes, in contrast to the control membrane. The cells on the control were aggregated regardless of the existence of divalent cations in the medium.

Adsorption↗

Effects of steroid hormones and cyclosporine A on taurine-transporter activity in the RAW264.7 cell line.

The activity of the taurine transporter is affected by various extracellular stimuli, such as ions, hormones and stress. To assess the effects of steroid hormones and cyclosporine A (CsA) on taurine-transporter activity, the murine monocytic cell line, RAW264.7, was stimulated with dexamethasone (DM), triamcinolone (TA), cortisone (CS), hydrocortisone (HCS), prednisone (PSN), prednisolone (PSL) and methylprednisolone (MPSL) in the presence of 12-O-tetradecanoylphorbol 13-acetate (TPA). Treatment of the cell with TPA led to a significant reduction in taurine-transporter activity. However, in the case of the stimulation of the cells with steroid hormones in the presence of TPA, all of the hormones reversed the TPA-induced reduction in the taurine-transporter activity. Treatment of the cells with CsA led to a significant reduction in taurine-transporter activity, but ionomycin (IM) alone did not affect taurine-transporter activity. However, IM reversed the TPA- and CsA-induced reduction in taurine-transporter activity. These results showed that both IM and the glucocorticoid hormones reversed TPA-induced reductions in taurine-transporter activity but only IM reversed the CsA-induced reduction of transporter activity in the RAW264.7 cell line.

Animals↗

Prediction of facial nerve displacement in extra large vestibular schwannoma.

The primary objective in the surgery of extra large vestibular schwannoma is the total removal of the tumour mass while preserving the facial nerve. Preservation of the facial nerve in extra large tumours is reported as being notoriously difficult in the majority of cases. This study was undertaken to evaluate the accuracy in predicting displacement of the facial nerve by preoperative radiological imaging studies in 19 cases of extra large vestibular schwannoma. The direction of displacement of the facial nerve was predicted with preoperative axial and coronal MRI scans and verified intraoperatively. We achieved total removal of tumours in 84.2%, facial nerve displacement was predicted in 80% and we accomplished anatomical preservation in 80%. Prediction of displacement was difficult in tumours with little or no intracanalicular components or with severe bony destruction of the internal acoustic meatus. The preoperative prediction of facial nerve displacement in extra large tumours allows safe internal decompression of the tumour and careful dissection near the predicted area of the facial nerve during the operation. Consequently, a high rate of anatomical preservation of the facial nerve can be achieved.

Decompression, Surgical↗

Effects of nitrogenous components of urine on sperm motility: an in vitro study.

The effects of the major nitrogenous components of urine (ammonia, creatinine, urea and uric acid) on sperm motility were investigated. Semen samples were obtained by masturbation from a young volunteer with a normal spermiogram and fertility. Sperm motility was measured using a Sperm Quality Analyzer and Makler Chamber. When semen was mixed with a urine sample for which acidity and osmolality were adjusted to pH 7.5 and 340 mOsm/kg, the higher the concentration of the urine, the poorer the sperm motility. When solutions of various concentrations of the nitrogenous compounds which are excreted in urine were mixed with semen, sperm motility decreased in proportion to ammonia levels and was markedly decreased after 30 min. However, in the case of creatinine, urea and uric acid, good motility was maintained for 30 min regardless of their amounts. In conclusion, urine ammonia content is detrimental to sperm motility and may be an important factor in retrograde ejaculation.

Adult↗

Inhibitory effect of calyculin A, a Ser/Thr protein phosphatase type I inhibitor, on renin secretion.

We have recently shown that several putative selective inhibitors of Ca2+-calmodulin-dependent myosin light chain kinase (MLCK), such as ML-9 [1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine], reversibly stimulate renin secretion [C. S. Park, S.-H. Chang, H. S. Lee, S.-H. Kim, J. W. Chang, and C. D. Hong. Am. J. Physiol. 271 (Cell Physiol. 40): C242-C247, 1996]. We hypothesized that Ca2+ inhibits renin secretion, via phosphorylation of 20-kDa myosin light chain (MLC20), by activating MLCK. In the present studies, we have investigated the types of protein phosphatase (PP) involved in the control of renin secretion through inhibition of MLC dephosphorylation using inhibitors of various types of serine/threonine-specific protein phosphatases. Cyclosporin A, a putative inhibitor of PP type 2 (calcineurin), was without effect. Calyculin A and okadaic acid, putative selective inhibitors of both PP type 1 (PP1) and type 2A (PP2A), significantly inhibited renin secretion under control conditions. Calyculin A had inhibitory effects at least 10-fold more potent than okadaic acid, suggesting that PP1, rather than PP2A, is involved in the control of renin secretion. Furthermore, calyculin A blocked the reversal of renin secretion preinhibited by raised intracellular Ca2+ concentrations in a concentration-dependent manner. Calyculin A (10(-6) M) significantly inhibited renin secretion stimulated by lowering intracellular Ca2+ concentrations and blocked the stimulatory effect of ML-9 on renin secretion. Taking all of these results into consideration, we hypothesize that dephosphorylation of MLC20 by Ca2+-independent PP1 stimulates renin secretion, whereas phosphorylation of MLC20 by Ca2+-calmodulin-dependent MLCK inhibits it. This hypothesized regulatory model of renin secretion predicts that the rate of renin secretion at a given time is determined by the ratio of phosphorylated to dephosphorylated MLC20, which is, in turn, determined by the dynamic balance between activity of MLCK and MLC phosphatase.

Animals↗

Atypical congenital kyphosis. Report of two cases with long-term follow-up.

We describe two patients with an atypical congenital kyphosis in which a hypoplastic lumbar vertebral body lay in the spinal canal because of short pedicles. There were no defects in the posterior elements, or any apparent instability of the facet joints. Both patients were treated successfully by anterior fusion to the levels immediately above and below the affected vertebra, and posterior fusion which extended one level more both proximally and distally. This gave progressive correction of the kyphotic deformity by allowing some continued anterior growth at the levels which had been fused posteriorly.

Humans↗

Regulation of renin secretion through reversible phosphorylation of myosin by myosin light chain kinase and protein phosphatase type 1.

Possible involvement of reversible phosphorylation and dephosphorylation of myosin light chain (MLC) by myosin light chain kinase (MLCK) and protein phosphatases (PPases), respectively, in the Ca++-calmodulin-dependent inhibition of renin secretion was investigated with the use of putative MLCK inhibitor ML-7 [1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine] and PPase type1 (PPase-1) and type 2A (PPase-2A) inhibitor calyculin A. ML-7 (1 x 10(-)6 to 3 x 10(-)5 M) increased renin secretion in vitro from rat renal cortical slices under "resting" conditions in a concentration-dependent manner with maximal 2.5-fold stimulation. Furthermore, Ca++-induced inhibition of renin secretion in depolarizing K+-rich Krebs-Ringer bicarbonate not only was prevented completely but also reversed by ML-7 in a concentration-dependent and reversible manner. On the other hand, calyculin A (3 x 10(-)6 M) blocked both effects of ML-7 on stimulation and reversal of renin secretion independently of intracellular Ca++ concentrations. Such antagonistic effects of ML-7 and calyculin A on renin secretion most likely resulted from their respective effects on the level of MLC phosphorylation: ML-7 stimulates renin secretion by decreasing phosphorylation of MLC through its inhibition of MLCK, whereas calyculin A inhibits secretion by increasing phosphorylation of MLC through its inhibition of PPase-1. By inference from these results, MLC may be the target protein involved in regulation of the renin secretory process by Ca++: Ca++-calmodulin phosphorylates MLC via activating MLCK and thereby inhibits renin secretion, whereas dephosphorylation of phosphorylated MLC by PPase-1 reverses the inhibited secretion. We therefore conclude that reversible phosphorylation of MLC may be an important biochemical step determining the rate of renin secretion from the juxtaglomerular cell.

Animals↗

Spine update. The management of scoliosis in neurofibromatosis.

When evaluating patients with neurofibromatosis and scoliosis, a careful search for the evidence of dystrophic changes should done, because prognosis and management depend highly on the presence of these changes. Preoperative imaging studies including computed tomography or magnetic resonance imaging are recommended, especially in cases of dystrophic scoliosis, to detect unrecognized intraspinal lesions. The radiographic findings and the response to treatment in patients with nondystrophic scoliosis are similar to those in patients with idiopathic scoliosis, and the same decision-making process for idiopathic scoliosis is applicable. Careful follow-up evaluation is mandatory, however, because of the tendency for extraordinary progression to occur with growth. Brace treatment of the short, angulated, dystrophic curves is ineffective; early and aggressive surgical intervention is strongly recommended. In most cases, dystrophic curvatures are best treated with combined anterior and posterior spinal arthrodesis. The fusion area should be generous, and the entire structural area of the deformity both anteriorly and posteriorly should be fused.

Adolescent↗