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Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 235 records · Page 13Linked to original sources

Combination chemotherapy of intermediate-dose cytarabine, idarubicin, plus etoposide and subsequent mobilized donor leukocyte infusion for relapsed acute leukemia after allogeneic bone marrow transplantation.

The efficacy and side effects of intermediate-dose cytarabine, idarubicin plus etoposide and subsequent donor leukocyte infusion (DLI) were investigated in patients with acute leukemia who relapsed after allogeneic bone marrow transplantation (BMT). Patients were given cytarabine continuous i.v. (1 g/m2 per day x 5), idarubicin i.v. (12 mg/m2 per day x 3), and etoposide i.v. infusion (150 mg/m2 per day x 3). Two days later, G-CSF mobilized donor leukocytes were infused for 2 days. No graft-versus-host disease (GVHD) prophylaxis was given. Between August 1997 and February 2000, 13 patients enrolled (eight acute myeloid leukemia (AML) and five acute lymphoblastic leukemia (ALL)). All patients finished chemotherapy and DLI. Eleven patients (85%) achieved complete remission (CR) at median 27 days after DLI. After median follow up of 10.9 months (2.5-33.3), five of 11 patients who achieved CR relapsed. Overall, six of 13 patients were surviving (6/8 AML and 0/5 ALL, P=0.059). Marrow recovery after chemotherapy and DLI was rapid (12 days for absolute neutrophil count (ANC) >500/microl). Side effects included fever with neutropenia (100%), pneumonia (46%), grade II-IV mucositis (69%), grade III-IV acute GVHD (45%), and extensive chronic GVHD (64%). One patient died from chronic GVHD. Chemotherapy containing intermediate-dose cytarabine and DLI produced a high CR rate in acute leukemia in relapse after allogeneic BMT. A fraction of patients are surviving long term. Side effects were substantial but manageable.

Actuarial Analysis↗

CAG repeats of CTG18.1 and KCNN3 in Korean patients with bipolar affective disorder.

BACKGROUND: Trinucleotide repetition combined with variable penetrance of expression could be responsible for the complex transmission pattern observed in bipolar affective disorder (BPAD). The purpose of this study was to investigate the association of excess longer allele of KCNN3 and CTG18.1 in the patients with BPAD. METHODS: CAG/CTG repeat distribution in KCNN3, CTG 18.1 and ERDA1 was examined and the copy number of ligation product in repeat expansion detection (RED) was measured in Korean bipolar patients in comparison to ethnically matched healthy controls. RESULTS: No significant difference was found in the allele distribution of those repeats between bipolar patients and controls. Ligation product size in RED was not increased in bipolar patients. However, the copy number of ligation product in RED was highly correlated with CAG/CTG copies of ERDA1 (P=0.0001), partly with CTG 18.1 (P=0.04), but not with KCNN3. CONCLUSIONS: A longer CAG repeat alleles of KCNN3 or CTG 18.1 may not be a risk factor for BPAD in Korean population and the copy number of ligation product in RED in the patients with BPAD is influenced by the longer allele of CAG/CTG of ERDA1 or CTG 18.1.

Adult↗

The feasibility and safety of fluoroscopy-guided percutaneous intramyocardial gene injection in porcine heart.

BACKGROUND: Catheter-based transendocardial gene injection would be useful for the delivery of genes into the heart. We examined the feasibility and safety of percutaneous intramyocardial gene injections with fluoroscopic guidance alone. METHODS: We performed the procedure through an 8F arterial sheath inserted into the left carotid artery. In protocol 1, a mixture of India ink and normal saline was injected through a needle injection catheter in six pigs. We monitored blood pressure and ECG continuously during the procedure. Echocardiography, left ventriculography, and coronary angiography were performed. All pigs were sacrificed 2 days later and hearts were harvested. In protocol 2, a mixture of India ink and plasmid encoding CAT gene was injected in the same manner in eight pigs. Myocardial tissue was obtained 7 days after the procedure to assess gene expression. In protocol 3, four pigs were intentionally needle-perforated in the ventricular wall and were observed for 7 days. RESULTS: In protocol 1, there was no significant hemodynamic changes or serious arrhythmias during the procedure. Echocardiography and angiography revealed no evidence indicating pericardial effusion or wall motion abnormalities. Harvested hearts revealed one intramyocardial hematoma in a total of 36 injection sites. In protocol 2, the gene expression could be identified in 39 sites out of 48 injections after 7 days. In protocol 3, no animal showed signs indicating cardiac tamponade during the observation period. CONCLUSIONS: Our data suggest that fluoroscopy-guided percutaneous intramyocardial gene injection is a feasible and safe procedure, with no indication of associated significant hemodynamic changes, arrhythmias, or mortality.

Administration, Cutaneous↗

Mitochondrial transcription factor A (mtTFA) and diabetes.

Mitochondrial DNA (mtDNA) content decreased in an age-dependent manner and may be one of the causal factors in age-related type 2 diabetes. Mitochondrial transcription factor A (mtTFA), which provides the replication primer, plays a key role for the regulation of mtDNA replication and its level is proportional to mtDNA. Here, we studied on the regulatory mechanism of mtTFA expression and the factors affecting the transcriptional activity of the mtTFA promoter. The promoter of human mtTFA contains 67 CpG dinucleotides. When the plasmids bearing the mtTFA promoter (2378 bp) linked to luciferase were transiently transfected into HepG2 cells, in vitro methylation of NRF-1 site by HhaI methylase abolished the mtTFA promoter activity up to 90%, implying that the CpG methylation of NRF-1 site inactivate mtTFA promoter-driven transcriptional activity. Besides the promoter methylation, the exogenous hydrogen peroxide or glucose also modulates the promoter activity of mtTFA. The bacterially overexpressed mtTFA protein exhibits a strong binding affinity to circular DNA (perhaps to mtDNA in mitochondria in vivo) and the protection of the DNA from cleavage by a hydrogen peroxide attack. Taken all these results together, age-related alterations of oxidative stress may affect mtDNA replication via regulating mtTFA activity. Furthermore, a vicious cycle may be present between mtTFA protein level and oxidative stress in the sense of DNA damage. Further studies were necessary to prove the presence of methyl cytosine in the mtTFA promoter of either an aged or a diabetic person and the effect of oxidative stress on the mtTFA function and expression resulting in a change of the mtDNA copy number.

Amino Acid Sequence↗

Mixture of N-carbamoyl-L-glutamate plus L-arginine can protect rats with liver cirrhosis from acute ammonia intoxication.

BACKGROUND/AIMS: We earlier reported that N-carbamoyl-L-glutamate (CG) plus L-arginine (Arg) protected normal and 70% hepatectomized rats from intoxication by a lethal or sub-lethal dose of ammonium acetate, respectively. In the present study, the protective effect of these compounds on cirrhotic rats was assessed. METHODS: CG plus Arg were administered prior to the injection of a sub-lethal dose of ammonium acetate into dimethylnitrosamine-induced cirrhotic rats. Control rats were given phosphate-buffered saline (PBS) instead of the mixture. The behavior of the rats was monitored until the time of sacrifice. Blood ammonia level, blood urea nitrogen (BUN) and liver carbamoylphosphate synthetase I (CPS I) activity were determined. RESULTS: Pretreatment of rats with the mixture of CG plus Arg could significantly lower the blood ammonia level (P<0.05), increase the activity of CPS I (P<0.05), improve abnormal behavior associated with ammonia intoxication (P<0.05), and increase BUN (P<0.05), as compared with the PBS-injected control group. There were significantly close correlations between (1) the increase of CPS I activity; (2) the improvement of abnormal behavior; (3) the increase of BUN; and (4) the decrease of the blood ammonia level. CONCLUSIONS: A mixture of CG plus Arg could protect rats with liver cirrhosis from acute ammonia intoxication.

Acetates↗

Efficacy of histopathology in detecting petrochemical-induced toxicity in wild cotton rats (Sigmodon hispidus).

A variety of chemical mixtures exist in the soil of petrochemical waste sites, and many of these compounds are known immunotoxicants that have been observed to induce immune alterations in wild rodents inhabiting many of these petrochemical waste sites. Conventional histopathological assessments have been widely used with considerable success to investigate immunotoxicity of various agents under laboratory conditions. We hypothesized that histopathologic assessments would be equally sensitive for detecting exposure to complex mixtures of toxicants in cotton rats (Sigmodon hispidus) residing in contaminated habitats. Histopathological parameters were examined from a total of 624 cotton rats that were seasonally collected from 13 petrochemical-contaminated waste sites and 13 ecologically matched reference sites in Oklahoma over a 3-year period. Histopathological examination did not reveal any lesion associated with exposure to petrochemical wastes except renal inclusion bodies. Prevalence and severity of histologic lesions in liver and kidneys of cotton rats were significantly influenced by season, where prevalence and severity were lower in winter than summer on all study sites. These results suggest that the evaluation of toxicity from exposure to contaminants in the soil of industrial waste sites using histopathological assessments is not sensitive enough to detect exposure to the low levels of environmental contaminants present on most waste sites.

Animals↗

Effect of ginsenosides on voltage-dependent Ca(2+) channel subtypes in bovine chromaffin cells.

In previous reports we have shown that ginsenosides inhibit high threshold voltage-dependent Ca(2+) channels in neuronal cells. However, these studies did not show whether ginsenosides-induced inhibition of Ca(2+) currents discriminates among the various Ca(2+) channel subtypes, although it is known that there are at least five different Ca(2+) channel subtypes in neuronal cells. In this study we investigated the effect of ginsenosides on high threshold voltage-dependent Ca(2+) channel subtypes using their selective Ca(2+) channel blockers nimodipine (L-type), omega-conotoxin GVIA (N-type), or omega-agatoxin IVA (P-type) in bovine chromaffin cells. We could observe that ginsenosides inhibited high threshold voltage-dependent Ca(2+) currents in a dose-dependent manner. The IC(50) was about 120 microgram/ml. Nimodipine had no effect on ginsenosides response. However, the effect of ginsenosides on Ca(2+) currents was reduced by omega-conotoxin GVIA, omega-agatoxin IVA, and mixture of nimodipine, omega-conotoxin GVIA, and omega-agatoxin IVA. These data suggest that ginsenosides are negatively coupled to three types of calcium channels in bovine chromaffin cell, including an omega-conotoxin GVIA-sensitive (N-type) channel, an omega-agatoxin IVA-sensitive (P-type) channel and nimodipine/omega-conotoxin GVIA/omega-agatoxin VIA-resistant (presumptive Q-type) channel. Thus, the selective regulation of voltage-dependent Ca(2+) subtypes by ginsenosides in bovine chromaffin cell could be the cellular basis of antistress effects induced by ginseng.

Animals↗

Serum melanotransferrin, p97 as a biochemical marker of Alzheimer's disease.

The protein melanotransferrin (p97) is associated with the brain lesions of Alzheimer's disease (AD) and is a potential marker of the disorder. We measured serum p97 concentrations in 211 subjects: 71 patients with AD, 56 patients with non-AD-type dementia, and 84 normal control subjects. Serum p97 concentrations were elevated 3- to 4-fold in AD (median 15.00 pg/microl, interquartile range 10.20-17.00 pg/microl) as compared to non AD dementia (2.85 pg/microl, 1.93-7.15 pg/microl) and normal controls (3.20 pg/microl, 2.55-3.95 pg/microl). The mean elevation was significant at 13.54 +/- 3.72 pg/microl, even in the 38 subjects with mild AD (CDR stage 0.5-1). Receiver operating characteristic analyses confirmed an optimal diagnostic threshold of 10.0 pg/microl, which yielded over-all accuracy of 0.882 to 0.915. Serum p97 is a candidate marker of AD, even in the early stage when clinical diagnosis is most uncertain.

Adult↗

Improvement of generalization ability for identifying dynamical systems by using universal learning networks.

This paper studies how the generalization ability of models of dynamical systems can be improved by taking advantage of the second order derivatives of the outputs with respect to the external inputs. The proposed method can be regarded as a direct implementation of the well-known regularization technique using the higher order derivatives of the Universal Learning Networks (ULNs). ULNs consist of a number of interconnected nodes where the nodes may have any continuously differentiable nonlinear functions in them and each pair of nodes can be connected by multiple branches with arbitrary time delays. A generalized learning algorithm has been derived for the ULNs, in which both the first order derivatives (gradients) and the higher order derivatives are incorporated. First, the method for computing the second order derivatives of ULNs is discussed. Then, a new method for implementing the regularization term is presented. Finally, simulation studies on identification of a nonlinear dynamical system with noises are carried out to demonstrate the effectiveness of the proposed method. Simulation results show that the proposed method can improve the generalization ability of neural networks significantly, especially in terms that (1) the robust network can be obtained even when the branches of trained ULNs are destructed, and (2) the obtained performance does not depend on the initial parameter values.

Computer Simulation↗

Pyrolysis kinetics of waste PVC pipe.

The pyrolysis kinetics of waste PVC pipe was investigated with a thermal gravimetric analysis system at heating rates of 5, 10, and 30 degrees C/min in a nitrogen atmosphere. Freeman-Carroll method was employed to evaluate kinetic parameters. Two dominant peaks were observed on derivative gravimetric curves, hypothetically suggesting a two-stage apparent reaction model. The first-stage reaction was likely to be represented by stoichiometric reaction to yield volatiles (mainly HCl) and intermediates. The second-stage reaction might be described by thermal degradation of intermediates competitively into gas, liquid, and solid by-products. Quasi-isothermal operations were introduced to verify the reaction types of the first and second reaction. The generation reaction of intermediates achieved at lower temperatures was carried out independently with their decomposition reaction at higher temperatures. The effects of additives on the pyrolysis kinetics of waste PVC pipe seem to be significant, especially on the first-stage reaction. The first-stage reaction was retarded. A merged peak at low temperatures was observed on the derivative thermogravimetry (DTG) curve instead of two peaks usually observed for that of pure PVC resin. The first peak on the DTG curve of pure PVC resin may shift more, resulting in the complete overlap of two peaks. The quantity of evolved HCl was likely to decrease because of interaction of metal components of stabilizers with either HCl or active chlorine atom or both. The final residual fraction increased as a result of pyrolysis of organic forms of additives to yield extra char. On the other hand, the second-stage reaction kinetics demonstrates a similar pattern to that of pure PVC resin, implying that the effects of additives may be less significant in comparison with that at the first-stage reaction.

Chemical Phenomena↗

Age-related changes of glutathione content, glucose transport and metabolism, and mitochondrial electron transfer function in mouse brain.

To evaluate the oxidative stress-related parameters and to determine their order of appearance in the brain aging process, radionuclide experiments were carried out on male DBF1 mice at 3, 12, 24 and 30 months of age. The content of nonprotein sulfhydryl compounds, mainly glutathione, was estimated with technetium-99m meso-hexamethyl propyleneamine oxime ([99mTc]meso-HMPAO) tissue sampling. Glucose transport and metabolism was examined with [1-14C]2-deoxy-D-glucose (2-DG) tissue sampling. Mitochondrial electron transport function was estimated with [15O]O2 gas-tissue ARG. [99mTc]Meso-HMPAO uptake in brain expressed as standardized uptake value (SUV), (radioactivity in brain tissue/tissue weight)/(total administered radioactivity/body weight), reached maximum at 12 months of age and decreased at 24 and 30 months of age in every region examined. The pattern of 2-DG, expressed as SUV, showed a tendency to increase rather than decrease with aging. [15O]O2 fixation in brain slices remained constant until 24 months, while it decreased significantly at 30 months of age. The results suggested the possibility of using imaging techniques in vivo for longitudinal evaluation of the aging process and indicated reduction of nonprotein sulfhydryl compounds including GSH at the early stages of aging may also accelerate the dysfunction of mitochondrial electron transport and neurodegeneration.

Aging↗

Expression of gene for EIIIA- and EIIIB- fibronectin, fetal types of fibronectin, during gastric ulcer healing in rats.

Fibronectin (FN) is important for wound healing via cell proliferation, adhesion, differentiation, and matrix formation. Fetal types of FN mRNA, which include the region of EIIIA or EIIIB, are well expressed during embryonic development and wound healing. This study was done to investigate the mRNA expression of full-length FN, EIIIA- and EIIIB-FN, and the localization of FN in the gastric tissues during ulcer healing with northern blot analysis and immunohistochemical technique. Gastric ulcers in rats were produced by acetic acid. EIIIA- and EIIIB-FN mRNA were not detected in normal gastric tissues, but were expressed in the ulcerated tissues throughout the healing phase. However, on day 60 (in the scarred phase), the EIIIA- and EIIIB-FN mRNA had disappeared. The levels of full-length FN mRNA were increased from day 3 to 32 compared with the control levels, and decreased to the control levels on day 60. Full-length FN was predominantly localized at the mesenchyme around the infiltrating inflammatory cells in the granulation tissues and the basement membranes of the nonproliferating epithelial cells, which were regenerated at the ulcer margin. Thus, fetal gene transcripts of FN suggest the important role of fetal FN in gastric ulcer healing, mainly via the migration of mesenchymal and epithelial cells.

Animals↗

Etiology and prevention of substance use among Asian American youth.

Among populations identified by the U.S. Bureau of the Census, it is anticipated that the Asian/Pacific Islander (API) population will experience the greatest change between 1990 and 2050 (U.S. Bureau of the Census. [1996, February]. Current population reports. Series P25-1130. Washington, DC: U.S. Government printing office). Limited studies focus on APIs as a racial group and still fewer disaggregate samples to specific ethnic Asian subgroupings. This paper begins with definitions of the API communities, then examines rates of adolescent drug use, risk and protective factors, and preventive intervention effectiveness focused on API communities. The limited epidemiological data suggest that in general, APIs are at a relatively lower risk for drug use than youth from most other ethnic groups. However, the available data also suggest that use may not be as low as generally assumed with rates for alcohol use, smoking, and some illicit drugs being equal to or exceeding those of African Americans and European Americans. Despite the paucity of available data on particular Asian subgroups, the available data demonstrate that there are differences among API subgroups, underscoring the importance of identifying Asian subgroups when studying substance use and when planning prevention and treatment. The limited data examining the etiology of drug use across API subgroups suggests that some of the risk and protective factors derived from majority based research may also be predictors for these populations. These data support the utility of examining the generalizability of existing tested prevention approaches among different API communities. Finally, further efforts should be made to encourage and support the evaluation of community-based programs that already target and deliver services to API youth.

Adolescent↗

Cystic prostate metastases to the brain parenchyma: report of two cases and review of the literature.

Prostate carcinoma is among the leading causes of cancer death for American men. Intracranial metastases from prostatic adenocarcinoma are unusual, and cystic metastases are rare. Two cases of cystic intraparenchymal metastases from prostatic adenocarcinoma are reported. Our comprehensive literature review revealed that prostatic adenocarcinoma metastases are rarely diagnosed antemortem. If these lesions are detected early and treated with surgery and radiation therapy, survival time for patients with prostatic adenocarcinoma may be increased; however, given the rarity of these cases, routine CNS imaging of men with metastatic prostate cancer does not seem warranted.

Adenocarcinoma↗

Molecular cloning of a novel pathogen-inducible cDNA encoding a putative acyl-CoA synthetase from Capsicum annuum L.

By means of differential display, a pool of salicylic acid (SA)-induced mRNAs were identified and subsequently their cDNAs were isolated from a cDNA library prepared from SA-induced leaf tissues of hot pepper. One of these cDNA clones, designated CaSIG4, was 1900 bp and contained an open reading frame encoding 523 amino acids with a calculated molecular mass of 56.3 kDa. The predicted amino acid sequence of CaSIG4 showed high sequence similarity to the AMP-binding protein family of both prokaryotic and eukaryotic acyl-CoA synthetases. CaSIG4 transcripts accumulated rapidly after SA treatment and in response to both incompatible and compatible interactions with Xanthomonas campestris pv. vesicatoria race 1. To investigate the cis-acting elements mediating CaSIG4 expression, the CaSIG4 5'-flanking region was isolated by inverse PCR. Database searches indicated that a potential cis-regulatory element is almost identical to the consensus core sequences ACC(A/T)ACC(A/C) which are conserved among promoters of other phenylpropanoid biosynthetic genes. The subcellular localization of the CaSIG4 protein was studied by using a soluble modified GFP gene fusion delivered into epidermal cells of onion by biolistic bombardment. The CaSIG4-smGFP fusion protein was localized to the plasma membrane. Taken together, CaSIG4 encoding a putative acyl-CoA synthetase could function as a plasma membrane-bound protein with a role in signaling in plant defense.

Amino Acid Sequence↗

Intact Golgi synthesize complex branched O-linked chains on glycoside primers: evidence for the functional continuity of seven glycosyltransferases and three sugar nucleotide transporters.

We examined the functional co-localization and continuity of glycosyltransferases and sugar nucleotide transporters in the Golgi of two Chinese hamster ovary (CHO) cell lines that synthesize different types of O-linked oligosaccharides. CHO cells normally synthesize primarily Sia2,3Galbeta1,3GalNAc- on glycoproteins. CHO cells transfected with core-2 GlcNAc transferase (Core 2) can synthesize glycoproteins containing branched O-linked oligosaccharides with poly-N-acetyllactosamines. CHO lines incubated with [(3)H]galactose and GalNAc-alpha-phenyl (GAP) as a primer, synthesize labeled glycoside products that faithfully resemble those found on the endogenous acceptors: CHO cells make Sia2,3[(3)H]Gal(beta)1,3GAP, while CHO Core2 cells synthesize GAPs with complex branched chains including poly-N-acetyllactosamines. To determine if isolated Golgi preparations make similar products, we prepared Golgi by established homogenization methods, documented their intactness, and added tracer UDP-[(3)H]Gal, unlabeled sugar nucleotides, and GAP. CHO Golgi preparations synthesized only Sia2,3[(3)H]Gal(beta)1,3GAP. CHO Core2, also made this product and a small amount of Core-2 GlcNAc transferase-dependent products. No endogenous glycoproteins were labeled. However, when either cell line was gently permeabilized with streptolysin-O or given hypo-osmotic shock, both GAP and endogenous acceptors were efficiently glycosylated within an intact functional Golgi lumen and remained there. Significantly, Golgi from CHO Core2 cells made mostly branched GAP products including some with poly-N-acetyllactosamines as complex as those made and secreted by living cells incubated with GAP. These results suggest that the lumen of the Golgi apparatus is functionally continuous or interconnected. Once glycosides diffuse into the Golgi lumen, they have access to all the sugar nucleotide transporters and glycosyltransferases used for complex GAP-based products without requiring metabolic energy or inter-vesicular transport. Glycosylation of artificial acceptors could be used to track the functional continuity or co-localization of multiple glycosyltransferases and transporters under conditions where Golgi morphology disintegrates and/or reappears.

Animals↗

Genetic heterogeneity in Korean families with autosomal-dominant polycystic kidney disease (ADPKD): the first Asian report.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease in adults, and the prevalence of this disease within the chronic haemodialysis patient population is known to be approximately 2% in Korea. So far, three genetic locus have been identified as being responsible for ADPKD, and approximately 85% of the cases in Western countries are related to the PKD1 gene. However, little information is available concerning the pattern of linkage analysis in Asian populations. METHODS: 48 families with hereditary renal cysts were recruited by consent and their molecular genetic characteristics were studied. Linkage analysis was done with microsatellite markers (PKD1: SM7, UT581, AC2.5, KG8, D16S418; PKD2: D4S423, D4S1534, D4S1542, D4S1544, D4S2460). Genomic DNA polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) gel run were performed, and the resultant allele patterns were compared with sonographic findings. RESULTS: The results of this study showed that the ratio PKD1:PKD2 was 31:8, and that the PKD2 families exhibited a tendency toward a milder renal prognosis than the PKD1 families. CONCLUSION: We confirmed the applicability of linkage analysis for ADPKD in the Korean population, and our data confirmed a similar incidence of PKD1 (79%) and PKD2 (21%) in Korean patients as in the Western population.

Adolescent↗

Specific and nonspecific NK cell activation during virus infection.

The natural killer (NK) cell activation receptor Ly49H is required for resistance to murine cytomegalovirus (MCMV). We show here that NK cell proliferation and production of interferon-gamma (IFN-gamma) was not dependent on Ly49H expression during early MCMV infection. During a later phase of infection, however, Ly49H+ NK cells selectively proliferated and this expansion was blocked by anti-Ly49H administration. With vaccinia virus infection, neither the early nor late phase of NK cell proliferation was selective for Ly49H+ NK cells. These findings indicated that Ly49H+ NK cells were specifically activated by MCMV and that MCMV infection was characterized by nonspecific and specific phases of NK cell activation in vivo.

Animals↗