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Biomedical subjects

J Kim

Publications and source records attributed to J Kim.

At least 19 recordsLinked to original sources
PubMed2025

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is the first-line therapy for high-grade non-muscle-invasive bladder cancer (NMIBC), yet many patients experience recurrence due to immune evasion. We identify HLA-E and NKG2A as mediators of adaptive resistance involving chronic activation of NK and T cells in BCG-unresponsive tumors. Prolonged IFN-γ exposure enhances HLA-E and PD-L1 expression on recurrent tumors, accompanied by the accumulation of NKG2A+ NK and CD8 T cells. HLA-Ehigh tumor cells preferentially cluster near CXCL12-rich stromal regions with dense effector cell presence, underscoring a spatially segregated tumor architecture. Although cytotoxic lymphocytes retain effector potential, their activity is restrained by HLA-E/NKG2A and PD-L1/PD-1 pathways located in their immediate neighborhood within the bladder tumor microenvironment. These data reveal a spatially organized immune escape program that limits anti-tumor immunity. Our findings support dually targeting NKG2A and PD-L1 checkpoint blockade as a rational, bladder-sparing strategy for patients with BCG-unresponsive NMIBC.

BCG-unresponsive↗
PubMed2007

Cerebellar peduncular myelinolysis in a patient receiving hemodialysis.

Here, we report the observation of extrapontine lesions, in addition to the pontine lesions previously documented in a diagnosed case of hemodialysis-associated osmotic demyelination syndrome due to end-stage renal disease. The patient exhibited lesions on bilateral middle cerebellar peduncles, and had been receiving regular hemodialysis as treatment for end-stage renal disease. He presented with progressive gait disturbance and postural instability. Accompanying symptoms included peduncular hallucinations and mild cognitive dysfunction. Brain MRI revealed high signal intensity in the area of bilateral cerebellar peduncles on the diffusion and T2-weighted images, with a decreased signal intensity noted on the ADC map. The ataxic form of osmotic myelinolysis syndrome is quite rare. The involvement of the cerebellar peduncles in extrapontine myelinolysis in a patient with end stage renal disease has not, to our knowledge, been previously reported. Here, we describe the MRI findings and clinical features associated with this unique case, and include a review of the relevant literature.

Aged↗
PubMed2007

The sero-prevalence of antibodies to trypanosoma cruzi in Latin American refugees and immigrants to Canada.

BACKGROUND: Chagas' disease is caused by infection with the protozoan agent Trypanosoma cruzi. An estimated sixteen to eighteen million people are infected in Latin America. Outside of endemic regions, Chagas' disease may be transmitted through the transfusion of infected blood components, congenital infection and organ transplantation. We sought to determine the sero-prevalence of antibodies to T. cruzi in a community sample of Latin American refugees and immigrants to Canada. METHODS: This was a sero-prevalence study in Latin American refugees and immigrants living in Canada. Eligible subjects were born in South America, Central America or in Mexico. Participants were recruited from a variety of community settings, as well as from medical clinics. Serum was tested by enzyme-linked immunoassay for antibodies to T. cruzi. RESULTS: A total of 102 participants were enrolled. One sample tested positive for antibodies for T. cruzi. The seroprevalence in our sample was 1.0% (95% CI: 0.2%- 5.3%). INTERPRETATION: We found a low sero-prevalence of Chagas' disease in a community sample of Latin American immigrants and refugees. Physicians who treat Latin American immigrants should consider the risk profile and clinical status of the individual in their decision to screen for Chagas' disease.

Adolescent↗
PubMed2007

Human amniotic fluid-derived stem cells have characteristics of multipotent stem cells.

OBJECTIVES: To characterize mesenchymal stem cell-like cells isolated from human amniotic fluid for a new source of therapeutic cells. MATERIALS: Fibroblastoid-type cells obtained from amniotic fluid at the time of birth. METHODS: The ability of ex vivo expansion was investigated until senescence, and stem cell-like characteristics were analyzed by examining differentiation potential, messenger RNA expression and immunophenotypes. RESULTS AND CONCLUSIONS: A morphologically homogenous population of fibroblastoid-type (HAFFTs) cells, similar to mesenchymal stem cells from bone marrow (BM-MSCs), was obtained at the third passage. The cells became senescent after 27 passages over a period of 8 months while undergoing 66 population doublings. Under appropriate culture conditions, by the 8th passage they differentiated into adipocytes, osteocytes, chondrocytes and neuronal cells, as revealed by oil red O, von Kossa, Alcian blue and anti-NeuN antibody staining, respectively. Immunophenotype analyses at the 17th passage demonstrated the presence of TRA-1-60; SSEA-3 and-4; collagen types I, II, III, IV and XII; fibronectin; alpha-SMA; vimentin; desmin; CK18; CD44; CD54; CD106; FSP; vWF; CD31; and HLA ABC. Reverse transcriptase-polymerase chain reaction analysis of the HAFFTs from passages 6-20 showed consistent expression of Rex-1, SCF, GATA-4, vimentin, CK18, FGF-5 and HLA ABC genes. Oct-4 gene expression was observed up to the 19th passage but not at the 20th passage. HAFFTs showed telomerase activity at the 5th passage with a decreased level by the 21st passage. Interestingly, BMP-4, AFP, nestin and HNF-4alpha genes showed differential gene expression during ex vivo expansion. Taken together, these observations suggest that HAFFTs are pluripotent stem cells that are less differentiated than BM-MSCs, and that their gene expression profiles vary with passage number during ex vivo expansion.

Amniotic Fluid↗
PubMed2006

Balanced optical-microwave phase detectors for optoelectronic phase-locked loops.

A balanced optical-microwave phase detector for the extraction of low-jitter, high-power, and drift-free microwave signals from optical pulse trains is presented. The phase detection is based on electro-optic sampling with a differentially biased Sagnac loop. Because the timing information is transferred in the optical domain, the regenerated microwave signal is robust against drifts and photodetector nonlinearities. In a first experimental implementation, 3 fs in-loop relative timing jitter (integrated from 1 Hz to 10 MHz) between a 44 MHz optical pulse train and a 10.225 GHz microwave signal is demonstrated.

Journal Article↗
PubMed2006

A distributed model of carbohydrate transport and metabolism in the liver during rest and high-intensity exercise.

A model of reaction and transport in the liver was developed that describes the metabolite concentration and reaction flux dynamics separately within the tissue and blood domains. The blood domain contains equations for convection, axial dispersion, and transport to the surrounding tissue; and the tissue domain consists of reactions representing key carbohydrate metabolic pathways. The model includes the metabolic heterogeneity of the liver by incorporating spatial variation of key enzymatic maximal activities. Simulation results of the overnight fasted, resting state agree closely with experimental values of overall glucose uptake and lactate output by the liver. The incorporation of zonation of glycolytic and gluconeogenic enzyme activities causes the expected increase in glycolysis and decrease in gluconeogenesis along the sinusoid length from periportal to perivenous regions, while fluxes are nearly constant along the sinusoid length in the absence of enzyme zonation. These results confirm that transport limitations are not sufficient to account for the observed tissue heterogeneity of metabolic fluxes. Model results indicate that changes in arterial substrate concentrations and hepatic blood flow rate, which occur in the high-intensity exercise state, are not sufficient to shift the liver metabolism enough to account for the 5-fold increase in hepatic glucose production measured during exercise. Changes in maximal activities, whether caused by exercise-induced changes in insulin, glucagon, or other hormones are shown to be needed to achieve the expected glucose output. This model provides a framework for evaluating the relative importance to hepatic function of various phenomenological changes that occur during exercise. The model can also be used to assess the potential effect of metabolic heterogeneity on metabolism.

Carbohydrate Metabolism↗
PubMed2006

Looking different: understanding diversity in facial form.

The face is perhaps the most distinguishing feature of the vertebrate body. Six billion human faces decorate the earth, each of them unique and exceptional in their own way. Likewise, facial variation is the cornerstone of species-specific diversity within the animal kingdom. Yet despite this multiplicity in form, the underlying architecture of the vertebrate face is remarkably conserved. If early embryos of different species first resemble one another, then how is this facial diversity generated? Our primary goal is to elucidate the molecular origins of species-specific craniofacial morphogenesis. We examined one facial primordia, the frontonasal prominence, of phylogenetically related (chick vs. quail vs. duck) and distant (mouse vs. chick) embryos and asked how such drastically different forms (e.g., beak, bill, or muzzle) could be generated from a once-similar entity. We examined the morphological ontogeny and a number of molecular expression patterns in an attempt to shed light on when species-specific variations occur and what molecules (BMPs, FGFs, etc.) are implicated in its differential growth. We hypothesize that subtle changes in the signaling of these morphogens can reproducibly alter the morphology of the frontonasal prominence. Taken together, these data facilitate our fledgling understanding of the process by which facial morphogenesis is regulated.

Animals↗
PubMed2006

Prediction of thrombolytic efficacy in acute ischemic stroke using thin-section noncontrast CT.

Thin-section noncontrast CT (NCT) can detect thrombi in large arteries and can provide a measure of thrombus composition based on Hounsfield Units (HU). A study using polyethylene tubes as a model of intracranial arteries concluded that the HUs of platelet-rich thrombi are lower than those of erythrocyte-rich thrombi. Thrombus HUs were measured by NCT in 34 patients with acute ischemic stroke before thrombolysis. Thrombi with lower HU counts were resistant to thrombolytics.

Aged↗
PubMed2006

Stimulating effects on mouse splenocytes of glycoproteins from the herbal medicine Atractylodes macrocephala Koidz.

A traditional herbal medicine, Atractylodes macrocephala Koidz. (AMK), has long been used as a digestive and tonic. Recent investigations have suggested its potential ability in stimulating immune responses, although a scientific basis for this activity has not yet been elucidated. Based on previous results showing that the activity might be due to proteins, we purified protein samples from an original sample preparation of AMK and examined the stimulating ability of the protein samples on mouse splenocytes. The sample treatment markedly stimulated lymphocyte proliferation, antibody production, and cytokine secretion in mouse splenocytes. In particular, the samples showed the ability to induce the preferential stimulation of Th1 type, rather than Th2 type T lymphocytes. Stimulating activity of the samples was associated closely with glycoprotein(s) with molecular weights of around 30 kDa, especially with carbohydrate moiety rather than with protein residues of the glycoprotein(s). Our findings suggest that the glycoprotein(s) might play critical roles in modulating immune-response induction, and could potentially be used as medicinal and pharmacological agents.

Animals↗
PubMed2006

Core area scaling of Nd:Al-doped silica depressed clad hollow optical fiber and Q-switched laser operation at 0.9 microm.

We demonstrate a Q-switched, cladding-pumped, Nd:Al-doped silica depressed clad hollow optical fiber (DCHOF) laser, which generated up to 133 microJ of pulse energy at a repetition rate of 5 kHz and 0.9 W of average output power at a high repetition rate (>20 kHz) in a diffraction-limited beam (M(2)=1.08) at 927 nm. The laser was tunable from 919 to 935 nm. This result shows the potential of the DCHOF structure for the suppression of unwanted long-wavelength radiation in large-area cores suitable for high-power Q-switched laser operation.

Journal Article↗
PubMed2006

Attenuated pain responses in mice lacking Ca(V)3.2 T-type channels.

Although T-type Ca(2+) channels are implicated in nociception, the function of specific subtypes has not been well defined. Here, we compared pain susceptibility in mice lacking Ca(V)3.2 subtype of T-type Ca(2+) channels (Ca(V)3.2(-/-)) with wild-type littermates in various behavioral models of pain to explore the roles of Ca(V)3.2 in the processing of noxious stimuli in vivo. In acute mechanical, thermal and chemical pain tests, Ca(V)3.2(-/-) mice showed decreased pain responses compared to wild-type mice. Ca(V)3.2(-/-) mice also displayed attenuated pain responses to tonic noxious stimuli such as intraperitoneal injections of irritant agents and intradermal injections of formalin. In spinal nerve ligation-induced neuropathic pain, however, behavioral responses of Ca(V)3.2(-/-) mice were not different from those of wild-type mice. The present study reveals that the Ca(V)3.2 subtype of T-type Ca(2+) channels are important in the peripheral processing of noxious signals, regardless of modality, duration or affected tissue type.

Animals↗
PubMed2006

A comparative analysis of collagen VI production in muscle, skin and fibroblasts from 14 Ullrich congenital muscular dystrophy patients with dominant and recessive COL6A mutations.

Ullrich congenital muscular dystrophy (UCMD) is caused by recessive and dominant mutations in COL6A genes. We have analysed collagen VI expression in 14 UCMD patients. Sequencing of COL6A genes had identified homozygous and heterozygous mutations in 12 cases. Analysis of collagen VI in fibroblast cultures derived from eight of these patients showed reduced extracellular deposition in all cases and intracellular collagen VI staining in seven cases. This was observed even in cases that showed normal collagen VI labelling in skin biopsies. Collagen VI immunolabelling was reduced in all the available muscle biopsies. When comparisons were possible no correlation was seen between the extent of the reduction in the muscle and fibroblast cultures, the mode of inheritance or the severity of the clinical phenotype. Mutations affecting glycine substitutions in the conserved triple helical domain were common and all resulted in reduced collagen VI. This study expands the spectrum of collagen VI defects and shows that analysis of skin fibroblasts may be a useful technique for the detection of collagen VI abnormalities. In contrast, immunohistochemical analysis of skin biopsies may not always reveal an underlying collagen VI defect.

Adolescent↗
PubMed2006

Optimal medical therapy is superior to transplantation for the treatment of class I, II, and III heart failure: a decision analytic approach.

BACKGROUND: The survival benefit of heart transplantation (HT) compared with optimal medical therapy (OMT) has never been tested. METHODS AND RESULTS: We created a decision analytic model that simulates a randomized clinical trial of OMT versus HT for each New York Heart Association (NYHA) class. The simulation calculates average life expectancy. The following assumptions were made for OMT annual mortality: class I no excess mortality from HF; class II and III based on MERIT-HF are 5.3% and 8.1%. Class IV is 12.8%, based on COPERNICUS. HT mortality rates were based on survival curves for HT 1982 to 2001. For classes I, II, and III, OMT demonstrated a life expectancy gain of 113 months (232+/-2.2 versus 119+/-2.1), 38 months (152+/-2.1 versus 114+/-2.1), and 6 months (117+/-1.8 versus 111+/-2.2), respectively, over HT. Class IV favored HT with a life expectancy gain of 26 months (107+/-2.1 versus 81+/-1.4) over OMT. Sensitivity analysis revealed if improvement in OMT decreased mortality by 38% for class IV patients, OMT and HT would have equivalent life expectancies. If improvement in HT resulted in a 7% increase in post-HT survival, OMT and HT would be equivalent for class III patients. If improvement in HT resulted in a 30% increase in post-HT survival, OMT and HT would be equivalent for class II patients. CONCLUSIONS: Our model predicts that currently, OMT is superior to HT for classes I, II, and III, but HT is superior for class IV. However, future advances in OMT or HT may change the relative benefits of these treatment modalities.

Adrenergic beta-Antagonists↗
PubMed2006

Risk factors affecting blood PCDDs and PCDFs in residents living near an industrial incinerator in Korea.

The contamination sources of polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), such as industrial incinerators, can potentially change the blood levels and isomer patterns of PCDD/DFs in residents living near the incinerators. In this study, we estimated whether the blood levels and isomer patterns of PCDD/DFs in residents living near an incinerator were affected by its presence and investigated factors that characterize the risk of high exposure to PCDD/DFs in the area. We estimated the blood levels and homologue patterns of PCDD/DFs in a group of 40 residents living within 5 km of an industrial incinerator and in a group of 20 residents living 20 km away from an incinerator. We cannot assert that the operation of incinerator facilities was only cause of increased PCDD/DFs in these residents; however, the operation of incinerator facilities in agricultural areas increased PCDD/DF exposure to individuals. The group living next to the industrial incinerator especially represented the typical isomer pattern in which the proportions of OCDDs were lower and those of PCDFs higher than those in the other groups. The high-risk population with increased blood levels of PCDD/DFs included those who had lived longer in the contaminated area as well as those who frequently ate contaminated foods.

Air↗
PubMed2006

15-Lipoxygenase-2 gene regulation by its product 15-(S)-hydroxyeicosatetraenoic acid through a negative feedback mechanism that involves peroxisome proliferator-activated receptor gamma.

An inverse relationship exists between the expression of 15-lipoxygenase-2 (15-LOX-2) and peroxisome proliferator-activated receptor gamma (PPARgamma) in normal prostate epithelial cells (PrECs) compared with their expression in prostate carcinoma cells (PC-3). The reason for this difference, however, is unknown. We hypothesized that this inverse expression partly involves the 15-LOX-2 promoter and 15-S-hydroxyeicosatetraenoic acid (15-(S)-HETE), a product of 15-LOX-2 that binds to PPARgamma. We identified an active steroid nuclear receptor half-site present in the 15-LOX-2 promoter fragment F-5 (-618/+177) that can interact with PPARgamma. After forced expression of wild-type PPARgamma, 15-(S)-HETE (1 microM) decreased F-5 reporter activity in PrECs whereas forced expression of 15-LOX-2 resulted in 15-(S)-HETE production which enhanced F-5 activity in PC-3. In contrast, the expression of dominant-negative PPARgamma reversed the transcriptional activation of F-5 by enhancing it 202-fold in PrEC or suppressing it in PC-3; the effect in PC-3 was positively increased 150-fold in the presence of 15-(S)-HETE (1 microM). Peroxisome proliferator-activated receptor gamma interacted with 15-LOX-2 promoter sequences in pulldown experiments using biotinylated 15-LOX-2 (-560/-596 bp) oligonucleotides. In gelshift analyses PPARgamma and orphan receptor RORalpha were shown to interact with the F-5 fragment in PC-3 cells. These data suggest that crosstalk mechanisms exist between the 15-LOX-2 gene and PPARgamma to counterbalance expression and help explain the inverse relationship of these genes in normal versus cancer cells.

5' Untranslated Regions↗
PubMed2006

Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins.

BACKGROUND: Despite intent to cure surgery with negative resection margins, locoregional recurrence is common in pancreatic cancer. AIMS: To determine whether detection of K-ras gene mutation in the histologically negative surgical margins of pancreatic cancer reflects unrecognised disease. PATIENTS: Seventy patients who underwent curative resection for pancreatic ductal adenocarcinoma were evaluated. METHODS: All patients had surgical resection margins (pancreatic transection and retroperitoneal) that were histologically free of invasive cancer. DNA was extracted from these paraffin embedded surgical margins and assessed by quantitative real time polymerase chain reaction to detect the K-ras gene mutation at codon 12. Detection of K-ras mutation was correlated with standard clinicopathological factors. RESULTS: K-ras mutation was detected in histologically negative surgical margins of 37 of 70 (53%) patients. A significant difference in overall survival was demonstrated between patients with margins that were K-ras mutation positive compared with negative (median 15 v 55 months, respectively; p = 0.0008). By univariate and multivariate analyses, detection of K-ras mutation in the margins was a significant prognostic factor for poor survival (hazard ratio (HR) 2.8 (95% confidence interval (CI) 1.5-5.3), p = 0.0009; and HR 2.8 (95% CI 1.4-5.5), p = 0.004, respectively). CONCLUSIONS: Detection of cells harbouring K-ras mutation in histologically negative surgical margins of pancreatic cancer may represent unrecognised disease and correlates with poor disease outcome. The study demonstrates that molecular-genetic evaluation of surgical resection margins can improve pathological staging and prognostic evaluation of patients with pancreatic ductal adenocarcinoma.

Adenocarcinoma↗
PubMed2006

Caudate blood flow and volume are reduced in HIV+ neurocognitively impaired patients.

OBJECTIVE: To evaluate the effects of HIV-associated neurocognitive impairment on caudate blood flow and volume. METHODS: The authors performed continuous arterial spin labeled MRI on 42 HIV+ patients (23 subsyndromic and 19 HIV neurosymptomatic) on highly active antiretroviral therapy and 17 seronegative controls. They compared caudate blood flow and volume among groups. RESULTS: A stepwise decrease in both caudate blood flow and volume was observed with increasing HIV-associated neurocognitive impairment. Compared with seronegative controls, baseline caudate blood flow was reduced in HIV+ neurosymptomatic patients (p = 0.001) with a similar decreasing trend for subsyndromic HIV+ patients (p = 0.070). Differences in caudate volume were observed only for neurosymptomatic HIV+ patients compared with controls (p = 0.010). A Jonckheere-Terpstra test for trends was significant for both caudate blood flow and volume for each of the three subgroups. Pearson product moment correlation coefficients were not significant between caudate blood flow and volume for each group. CONCLUSIONS: Decreasing trends in caudate blood flow and volume were associated with significantly increasing HIV-associated neurocognitive impairment (HNCI), with the greatest decreases observed for more severely impaired patients. However, reductions in caudate blood flow and volume were poorly correlated. Changes in residual caudate blood flow may act as a surrogate biomarker for classifying the degree of HNCI.

AIDS Dementia Complex↗