Biomedical subjects

M Shin

Publications and source records attributed to M Shin.

At least 19 recordsLinked to original sources

PubMed2006

The genome of the obligately intracellular bacterium Ehrlichia canis reveals themes of complex membrane structure and immune evasion strategies.

Ehrlichia canis, a small obligately intracellular, tick-transmitted, gram-negative, alpha-proteobacterium, is the primary etiologic agent of globally distributed canine monocytic ehrlichiosis. Complete genome sequencing revealed that the E. canis genome consists of a single circular chromosome of 1,315,030 bp predicted to encode 925 proteins, 40 stable RNA species, 17 putative pseudogenes, and a substantial proportion of noncoding sequence (27%). Interesting genome features include a large set of proteins with transmembrane helices and/or signal sequences and a unique serine-threonine bias associated with the potential for O glycosylation that was prominent in proteins associated with pathogen-host interactions. Furthermore, two paralogous protein families associated with immune evasion were identified, one of which contains poly(G-C) tracts, suggesting that they may play a role in phase variation and facilitation of persistent infections. Genes associated with pathogen-host interactions were identified, including a small group encoding proteins (n = 12) with tandem repeats and another group encoding proteins with eukaryote-like ankyrin domains (n = 7).

Animals↗

PubMed2004

Contractile cardiac grafts using a novel nanofibrous mesh.

Cardiomyoctes are terminally differentiated cells and therefore unable to regenerate after infarction. The use of autologous bioengineered cardiac grafts has been suggested to replace infarcted myocardium and enhance cardiac function. Here we report the development of an in vitro system for engineered myocardium. Cardiac nanofibrous meshes (CNM) were developed by culturing cardiomyocytes from neonatal Lewis rats on electrospun, nanofibrous polycaprolactone (PCL) meshes. The mesh had an ECM-like topography and was suspended across a wire ring that acted as a passive load to contracting cardiomyocytes. The cardiomyocytes started beating after 3 days and were cultured in vitro for 14 days. The cardiomyocytes attached well on the PCL meshes and expressed cardiac-specific proteins such as alpha-myosin heavy chain, connexin43 and cardiac troponin I. The results demonstrate the formation of contractile cardiac grafts in vitro. Using this technique, cardiac grafts can be matured in vitro to obtain sufficient function prior to implantation. It is conjectured that cardiac grafts with clinically relevant dimensions can be obtained by stacking CNMs and inducing vascularization with angiogenic factors.

Animals↗

PubMed2004

Assessment of tissue-engineered stomach derived from isolated epithelium organoid units.

OBJECTIVE: Isolated stomach epithelial organoid units developed on biodegradable polymers were transplanted to assess the feasibility of a tissue-engineered stomach. BACKGROUND: Despite recent advances in reconstruction techniques, total gastrectomy is still accompanied by various complications. An alternative treatment would be a tissue-engineered stomach, which replaces the mechanical and metabolic functions of a normal stomach. METHODS: Stomach epithelial organoid units isolated from neonatal rats were seeded onto biodegradable polymers. The constructs implanted into the omenta of adult rats were harvested for examination at designated times. Nine rats underwent a second operation for anastomosis. RESULTS: The constructs resulted in cyst-like formations showing vascularized tissue with neomucosa lining the lumen. The surface morphology as assessed using scanning electron microscopy was similar to that of a native stomach. Immunohistochemical staining for alpha-actin smooth muscle and gastric mucin indicated the presence of a smooth muscle layer and a well-developed gastric epithelium, respectively. The luminal surface of the anastomosed tissue-engineered stomach was well-covered with epithelium. CONCLUSIONS: Epithelium-derived stomach organoid units seeded on biodegradable polymers and transplanted into donor rats were shown to vascularize, survive, and regenerate into complex tissue resembling native stomach. Anastomosis between the units and native small intestine may have the potential to stimulate epithelial growth. This research may provide insight into new approaches to alleviate complications following total gastrectomy.

Animals↗

PubMed2004

Serial follow-up study of serum testosterone and antisperm antibodies in patients with non-obstructive azoospermia after conventional or microdissection testicular sperm extraction.

Testicular sperm extraction (TESE) combined with intracytoplasmic sperm injection is becoming a first-line treatment even for non-obstructive azoospermia. The current focus of TESE is the identification of seminiferous tubules that contain spermatozoa and minimization of testicular damage. Although microdissection TESE has been introduced as a preferred procedure for sperm retrieval, no serial follow-up studies of testicular damage have been reported. In the present study, we assayed serum testosterone concentrations and for the presence of antisperm antibodies (ASA) for 1 year after conventional multiple TESE or microdissection TESE and compared postoperative testicular damage between procedures. Thirteen patients who underwent conventional multiple TESE and 12 patients who underwent microdissection TESE were included in this study. Serum total and free testosterone concentrations were evaluated before operation and 1, 6 and 12 months after TESE. Serum ASA was also evaluated before and 12 months after TESE. Serum total and free testosterone concentrations in all patients in both groups showed no significant postoperative decrease. A comparison between the two groups of serum total and free testosterone concentrations showed no significant difference (total testosterone, p = 0.2477; free testosterone, p = 0.3098). No incidence of new ASA formation was identified in the present study. In conclusion, TESE procedures cause neither a decrease of serum testosterone nor formation of ASA. Serum testosterone concentration are similar between patients in the conventional multiple TESE and microdissection groups. Therefore, microdissection TESE is safe with respect to testicular damage, particularly for patients with hypogonadism.

Adult↗

PubMed2002

Two-dimensional thick-slice MR digital subtraction angiography in the assessment of small to medium-size intracranial arteriovenous malformations.

Assessment of intracranial arteriovenous malformations (AVMs) by conventional catheter angiography carries risks; moreover, this invasive procedure is often repeated for follow-up. We investigated the clinical applicability of two-dimensional thick-slice, contrast-enhanced magnetic resonance digital subtraction angiography (2D MRDSA) with high temporal resolution in the assessment of AVMs. We performed 78 2D MRDSA studies of treated or untreated small to medium-size AVMs on a 1.5 tesla imager. Two observers independently evaluated demonstration of nidus flow void on T2-weighted images and each component of the AVM on 2D MRDSA employing a three-point grading scale. In 55 patients with AVMs, the mean ratings of nidus flow voids, feeding vessels, nidi, draining vessels and early venous filling on MRI were 2.8, 2.4, 2.6, 2.8 and 2.8, respectively. sensitivity, specificity, positive and negative predictive values for an AVM using 2D MRDSA were 87, 100, 100 and 78%, respectively and for nidus flow voids on T2-weighted images 80, 91, 96 and 66%, respectively. 2D MRDSA can thus demonstrate haemodynamic features of AVMs. It can be employed as a less invasive, dynamic angiographic tool for follow-up of AVMs previously delineated by catheter angiography.

Adult↗

PubMed2002

Evaluation of support materials for the surface immobilization and decoloration of amaranth by Trametes versicolor.

The ability of Trametes versicolor ATCC 20869 to colonize several natural and synthetic materials (wheat straw, jute, hemp, maple woodchips, and nylon and polyethylene teraphthalate fibers) and to subsequently decolorize amaranth was evaluated. Jute was found to be the best support material as T. versicolor grew well on it without color leaching from the support and without loss of the jute's integrity over a 4 week period. The fungus immobilized on jute, straw and hemp decolorized amaranth (50 mg l(-1)) at a rate of about 5 mg l(-1) h(-1) without glucose being added. When 1 g l(-1) glucose was added, the dye was degraded more quickly (about 8 mg l(-1) h(-1)). Decoloration did not occur in a suspension culture without glucose. As the number of decoloration cycles increased, the rate of decoloration decreased. This rate was restored to its original level after the biomass was incubated in fresh growth medium for 5 days. With all immobilization supports, the toxicity of the medium before and after decoloration was the same or lower.

Amaranth Dye↗

PubMed2002

An inhibitor of c-jun aminoterminal kinase (SP600125) represses c-Jun activation, DNA-binding and PMA-inducible 92-kDa type IV collagenase expression.

The 92-kDa type IV collagenase (MMP-9) contributes to tumor invasion and metastases and strategies to down-regulate its expression could ultimately be of clinical utility. Although the expression of this collagenase is regulated by numerous growth factors, the signaling pathways that transduce these signals are fewer in number and therefore represent pharmacological targets. In this regard, we previously reported that MMP-9 expression was regulated by the c-jun amino terminal kinase (JNK) signaling cascade. Therefore, we undertook a study to determine the efficacy of a novel compound (SP600125), which binds to the ATP binding site of all known JNKs, in repressing MMP-9 expression. In OVCAR-3 cells, SP600125 inhibited the PMA-dependent secretion of MMP-9 in a time-dependent manner and over a dose range that blocked c-Jun phosphorylation and AP-1 binding. SP600125 repressed the activity of a PMA-stimulated MMP-9 promoter-driven luciferase reporter, suggesting that diminished secretion of this collagenase reflected reduced transcription. Further, the activity of a GAL4-driven reporter in PMA-treated cells, co-transfected with an expression construct encoding the trans-activation domain of c-Jun fused to the DNA binding domain of GAL4, was repressed by SP600125. These findings indicate the efficacy of SP600125 in inhibiting c-Jun activation, DNA-binding and the PMA-dependent induction of MMP-9 expression.

Anthracenes↗

PubMed2001

Potential mechanism for the effects of dexamethasone on growth of androgen-independent prostate cancer.

BACKGROUND: Dexamethasone, a synthetic glucocorticoid, has clinical benefit in patients with hormone-refractory prostate cancer (HRPC), but the mechanisms responsible for its effects are unknown. The nuclear factor-kappaB (NF-kappaB)-dependent cytokine interleukin (IL) 6 (IL-6) is thought to stimulate growth of HRPC. Because dexamethasone interferes with NF-kappaB activation, we determined whether dexamethasone inhibits prostate cancer growth by working through the glucocorticoid receptor (GR) to interfere with NF-kappaB-IL-6 pathway. METHODS: Three human prostate cancer cell lines (DU145, PC-3, and LNCaP) were assessed for GR expression and responsiveness to dexamethasone. Levels of GR, NF-kappaB, and the cytoplasmic NF-kappB inhibitor IkappaBalpha were determined by western blotting and of IL-6 by enzyme immunoassay. The subcellular localization of NF-kappaB was analyzed by immunofluorescence. The effects of dexamethasone (thrice weekly injections of 1 microg/mouse) on DU145 xenografts in nude and severe combined immunodeficient (SCID) mice were evaluated. GR expression in human prostate cancers was assessed by immunohistochemistry. All statistical tests were two-sided. RESULTS: Dexamethasone dose dependently decreased GR levels and inhibited the growth of DU145 and PC-3 but not LNCaP cells (DU145 cells, P< .001; PC-3 cells, P = .009). Dexamethasone increased IkappaBalpha protein levels and the cytosolic accumulation of NF-kappaB in DU145 cells and decreased secreted IL-6 levels to 37 pg/mL (95% confidence interval [CI] = 33 pg/mL to 41 pg/mL), compared with 164 pg/mL (95% CI = 162 pg/mL to 166 pg/mL) secreted by ethanol-treated control cells. Dexamethasone inhibited the growth of DU145 xenografts in nude (P = .006) and SCID (P = .026) mice without affecting GR levels. Eight of 16 human prostate cancers expressed GR at high levels (>or=30% GR-positive cells). CONCLUSION: Dexamethasone inhibited the growth of GR-positive cancers, possibly through the disruption of the NF-kappaB-IL-6 pathway.

Androgens↗

PubMed2001

Repression of deoP2 in Escherichia coli by CytR: conversion of a transcription activator into a repressor.

In the deoP2 promoter of Escherichia coli, a transcription activator, cAMP-CRP, binds at two sites, centered at -41.5 and -93.5 from the start site of transcription, while a repressor, CytR, binds to a space between the two cAMP-CRP complexes. The mechanisms for the cAMP-CRP-mediated transcription activation and CytR-mediated transcription repression were investigated in vitro using purified components. We classified the deoP2 promoter as a class II cAMP-CRP-dependent promoter, primarily by the action of cAMP-CRP at the downstream site. Interestingly, we also found that deoP2 carries an "UP-element" immediately upstream of the downstream cAMP-CRP site. The UP-element overlaps with the DNA site for CytR. However, it was observed that CytR functions with the RNA polymerase devoid of the C-terminal domain of the alpha-subunit as well as with intact RNA polymerase. The mechanism of repression by CytR proposed in this study is that the cAMP-CRP bound at -41.5 undergoes an allosteric change upon direct interaction with CytR such that it no longer maintains a productive interaction with the N-terminal domain of alpha, but instead acts as a repressor to interfere with RNA polymerase acting on deoP2.

Carrier Proteins↗

PubMed2001

Congestive brain oedema associated with a pial arteriovenous malformation with impaired venous drainage.

We describe two patients with an unruptured pial AVM accompanied by significant brain oedema at initial presentation. In both cases, the primary drainer was a cortical vein showing varicose dilatation. in which venous congestion was indicated by magnetic resonance imaging (MRI). The restriction of venous drainage presumably caused venous hypertension in the surrounding brain, leading to the brain oedema and neurological symptoms. Brain oedema can develop in patients with an unruptured AVM by venous congestion following spontaneous thrombosis of venous components. Varicosity in a major cortical draining vein and a small nidus are the possible lesions predisposing this fairly rare condition for unruptured AVMs.

Adolescent↗

PubMed2001

Capsazepine, a vanilloid receptor antagonist, inhibits the expression of inducible nitric oxide synthase gene in lipopolysaccharide-stimulated RAW264.7 macrophages through the inactivation of nuclear transcription factor-kappa B.

High amounts of nitric oxide (NO) production following the induction of inducible NO synthase (iNOS) gene expression has been implicated in the pathogenesis of inflammatory diseases. Capsaicin, a vanilloid receptor agonist, is known to have an inhibitory effect on NO production in macrophages. In the present study, we have found that capsazepine (CAPZ), a vanilloid receptor antagonist, also inhibited NO and iNOS protein syntheses induced by lipopolysaccharide in RAW264.7 macrophages via the suppression of iNOS mRNA. The mechanistic studies showed that CAPZ inhibited the expression of iNOS mRNA through the inactivation of nuclear transcription factor-kappa B (NF-kappa B). Thus, capsazepine may be a useful candidate for the development of a drug to treat inflammatory diseases related to iNOS gene overexpression.

Animals↗

PubMed2001

Successful radiosurgical treatment of lesional epilepsy of mesial temporal origin.

We report a case of successful radiosurgical treatment of lesional epilepsy of mesial temporal origin. A patient presented with a 2-year history of medically intractable complex partial seizures associated with a mesial temporal angioma. Interictal scalp EEG and MEG showed focal epileptiform activity around the lesion. 99mTc-HMPAO-SPECT and 18F-FDG-PET demonstrated depressed blood flow and glucose metabolism in the corresponding temporal lobe. The patient underwent gamma knife radiosurgery for the causative lesion with a low marginal dose of 18 Gy. After treatment, the partial attack ceased without shrinkage of the lesion or peri-lesional parenchymal radiation injury.

Adult↗

PubMed2001

Modulation of Chelidonii herba on GABA activated chloride current in rat PAG neurons.

Modulation of Chelidonii herba on gamma-aminobutyric acid (GABA) activated chloride current in the acutely dissociated periaqueductal gray (PAG) neuron was studied by nystatin-perforated patch-clamp technique. High concentrations of Chelidonii herba elicited ion current, that was blocked by bicuculline. Low concentrations reduced the GABA activated current in PAG. Two types of inhibitory action of Chelidonii herba on GABA activated current have been implicated in PAG. One is the inhibitory action of Chelidonii herba on GABA was abolished by naltrexone and the other is that of Chelidonii herba was potentiated by naltrexone. In addition, all of two types of action of Chelidonii herba are linked to pertussis toxin-sensitive GTP-binding proteins. These results suggest that the inhibitory modulation of Chelidonii herba on GABA activated current via G-proteins in PAG neuron is an important analgesic mechanism.

Animals↗

PubMed2001

Radiation-induced apoptosis of oligodendrocytes in the adult rat brain.

Although radiation injuries to the brain are well documented, immediate early histological changes in the brain remain to be defined. The present study characterizes glial injury provoked in adult rat white matter within 24 h after a single irradiation of the whole brain (10 or 20 Gray). Irradiated brains were histologically and histochemically analyzed. TUNEL-positive cells exhibiting apoptotic morphology were counted in five representative regions of the white matter. Glial cell death was further evaluated by glial cell density 24 h after irradiation, which induced both dose (p < 0.0001)- and time- (p < 0.0001) dependent apoptosis in these cells. The overall apoptotic rate in the white matter peaked within 8 h after irradiation. Total glial cell density decreased significantly in the white matter 24 h after irradiation. TUNEL-positive cells were immunohistochemically negative for GFAP, a marker for astrocytes, but positive for CNP, a marker for oligodendrocytes. The apoptotic rate was highest in the external capsule (p < 0.0001), followed by the fimbria and genu of the corpus callosum (p < 0.0001). The rates were lowest in the internal capsule and cerebellum. These data indicated that brain irradiation induces rapid apoptotic depletion of the oligodendroglial population, which may participate in the development of radiation-induced pathological conditions.

Age Factors↗

PubMed2001

Antisense-mediated inhibition of arginase (CAR1) gene expression in Saccharomyces cerevisiae.

Inhibition of Saccharomyces cerevisiae arginase (CAR1) gene expression was investigated using the antisense RNA technique. CAR1 DNA fragments containing the yeast CAR1 gene sequences from the transcription initiation site (-49) or translation initiation site (+1) to the +501 region were amplified using PCR and inversely fused to the yeast CYC1 promoter on the yeast YIp5 plasmid. These recombinant plasmids were transformed into yeast cells to construct strains containing CYC1 promoter-antisense CAR1 DNA in their chromosomal DNA. When the CAR1 DNA region from -120 to +552 was amplified by PCR, the CYC1 promoter-antisense CAR1 DNA plasmid transformants produced the same size of PCR fragments as vector only transformants, suggesting the recombinant plasmids did not integrate into the CAR1 loci. The level of arginase production by the recombinant transformants markedly decreased to about 15% of the enzyme activity produced by the vector only transformants.

Journal Article↗

PubMed2001

Analysis of treatment outcome after stereotactic radiosurgery for cavernous sinus meningiomas.

OBJECT: The long-term outcome of stereotactic radiosurgery for cavernous sinus (CS) meningiomas is not fully understood. The authors retrospectively reviewed their experience with 40 CS meningiomas treated with gamma knife radiosurgery. METHODS: Follow-up periods for the 40 patients ranged from 12 to 123 months (median 42 months), and the overall tumor control rates were 86.4% at 3 years and 82.3% at 10 years. Factors associated with tumor recurrence in univariate analysis were histological malignancy (p < 0.0001), partial treatment (p < 0.0001), suprasellar tumor extension (p = 0.0201), or extension in more than three directions outside the CS (p = 0.0345). When the tumor was completely covered with a dose to the margin that was higher than 14 Gy (Group A, 22 patients), no patient showed recurrence within the median follow-up period of 37 months. On the other hand, when a part of the tumor was treated with 10 to 12 Gy (Group B, 15 patients) or did not receive radiation therapy (Group C, three patients), the recurrence rates were 20% and 100%, respectively. Neurological deterioration was seen in nine patients, but all symptoms were transient or very mild. CONCLUSIONS: The data indicate that stereotactic radiosurgery can control tumor growth if the whole mass can be irradiated by dosages of more than 14 Gy. When optimal radiosurgical planning is not feasible because of a tumor's large size, irregular shape, or proximity to visual pathways, use of limited surgical resection before radiosurgery is the best option and should provide sufficient long-term tumor control with minimal complications.

Adult↗

PubMed2001

Failure of low-dose radiosurgery to control temporal lobe epilepsy.

Radiosurgical treatment of intractable epilepsy has emerged as a noninvasive alternative to resection. Although gamma knife surgery (GKS) reportedly is effective when the radiation dose is sufficient to cause a destructive reaction in the targeted medial temporal lobe, the optimal target area and dose distribution are largely unknown. Some investigators have suggested that focused irradiation from a nondestructive dose is also effective. In this article the authors report two cases of medial temporal lobe epilepsy in which the patients underwent GKS performed using a 50% marginal dose of 18 Gy covering the amygdala. hippocampal head and body, and parahippocampal gyrus. In both cases this procedure failed to control seizures. Both patients became seizure free after undergoing anterior temporal lobectomy 30 and 16 months, respectively, after radiosurgery.

Adult↗

PubMed2001

Development of virtual environment for treating acrophobia.

Virtual Reality (VR) is a new technology that makes humans communicate with computer. It allows the user to see, hear, feel and interact in a three-dimensional virtual world created graphically. Virtual Reality Therapy (VRT), based on this sophisticated technology, has been recently used in the treatment of subjects diagnosed with acrophobia, a disorder that is characterized by marked anxiety upon exposure to heights, avoidance of heights, and a resulting interference in functioning. Conventional virtual reality system for the treatment of acrophobia has a limitation in scope that it is based on over-costly devices or somewhat unrealistic graphic scene. The goal of this study was to develop a inexpensive and more realistic virtual environment for the exposure therapy of acrophobia. We constructed two types virtual environment. One is constituted a bungee-jump tower in the middle of a city. It includes the open lift surrounded by props beside tower that allowed the patient to feel sense of heights. Another is composed of diving boards which have various heights. It provides a view of a lower diving board and people swimming in the pool to serve the patient stimuli upon exposure to heights.

Altitude↗