Synthesis and in vitro evaluation of 4-substituted-1-azaanthraquinones.
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Anthraquinones↗
Biomedical subjects
J Cho
Publications and source records attributed to J Cho.
Role of the lateral mammillary nucleus in the rat head direction circuit: a combined single unit recording and lesion study.
We recorded head direction (HD) cells from the lateral mammillary nucleus (LMN) and anterior thalamus (ATN) of freely behaving rats and also made bilateral lesions of LMN while recording HD cells from ATN. We discovered that the tuning functions of LMN HD cells become narrower during contraversive head turns, but not ipsiversive head turns, compared to when the head is not turning. This narrowing effect does not occur for ATN HD cells. We also found that the HD signal in LMN leads that in ATN by about 15-20 ms. When LMN was lesioned bilaterally, HD cells in ATN immediately lost their directional firing properties and never recovered them. Based on these findings, we argue that LMN may be an essential component of an attractor-integrator network that participates in generating the HD signal.
Animals↗
Bilateral subperiosteal haematoma after endoscopic sinus surgery.
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Adolescent↗
Age-related changes in antioxidant enzyme activities in the small intestine and liver from Wistar rats.
The present study was designed to determine age-related changes in intestinal and hepatic antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and glutathione-S-transferase (GST), and lipid peroxidation in male Wistar rats (n = 8) aged 2 wk, 2.5 mon, 5 mon, 10 mon, and 23 mon. In the small intestine, cytosolic SOD, GSH-PX activities and lipid peroxidation were not affected by age, but intestinal GST activity was noticeably enhanced as age increased. In particular, intestinal GST activity in 23 mon old rats was 3 times as strong as that in 2 wk old rats. In the liver, the activity of hepatic cytosolic SOD was not affected by age, whereas GSH-PX and GST activities in rats aged 10 mon and 23 mon were much stronger than those in rats aged 2 wk, 2.5 mon, and 5 mon. The increased lipid peroxidation in 2.5 mon and 5 mon old rats was observed when compared with that of other groups. It is therefore concluded from the results presented here that age greatly increases GST activity in the small intestinal mucosae and increasing GSH-PX, GST activities and lipid peroxidation in the liver from male Wistar rats.
Aging↗
Epithelial ingrowth of anterior chamber and anterior surface of vitreous.
This study is a case report of the histopathologic findings of the anterior chamber epithelial ingrowth in a patient who had penetrating injury in the right eye from an arrow approximately 20 years ago. The patient underwent the enucleation in the right eye due to pthisis bulbi and was fitted with a prosthetic eye. Specimens were prepared from the enucleated right eye for histopathologic observation using hematoxyllin-eosin to be observed under light microscopy. Epithelial ingrowth in the anterior chamber was noted in one layer or multi-layered epithelial cell growth. The ingrowth had spread to the posterior surface of the cornea to the anterior chamber angle, to the iris surface, and to the anterior surface of the vitreous. The finding suggests that epithelial ingrowth could invade even through a perforation site and spread wherever the cells could reach.
Adult↗
Factors associated with the poor final visual outcome after traumatic hyphema.
In order to determine the factors related to the worse final visual outcome following nonperforating traumatic hyphema, the clinical characteristics of 18 patients with visual outcome of 0.1 or worse were compared with those of 166 patients with visual outcome of 0.15 or better. The presence of posterior segment injuries such as macula edema, retinal hemorrhage, epiretinal membrane, and choroidal rupture were significant factors of a poor final visual outcome (P < 0.01). The presence of anterior segment injuries such as corneal blood staining, traumatic mydriasis, iridodialysis, cataract, and lens subluxation had significant predictive factors on a poor final visual outcome and the concurrent posterior segment injuries were more frequent in these patients. Initial visual acuity of 0.1 or worse, glaucoma, vitreous hemorrhage, and eyelid laceration were also significant associations of a poor final visual outcome (P < 0.05). Patients with initially larger hyphema (grade I or more vs microscopic) and older age group (16 years or more vs 15 years or less) tended to have poor final visual acuities. Rebleeding was not associated with significant deterioration in visual prognosis. We conclude that the posterior segment injuries seem to be directly related to a poor visual outcome rather than the occurrence of secondary hemorrhage.
Adolescent↗
Pharmacodynamics of topoisomerase I inhibition: Western blot determination of topoisomerase I and cleavable complex in patients with upper gastrointestinal malignancies treated with topotecan.
Analogues of camptothecins are specific inhibitors of eukaryotic DNA topoisomerase I (topo I) that lead to DNA damage and, eventually, cellular cytotoxicity. Camptothecin analogues bind to this target enzyme in the course of its normal function and stabilize the DNA-enzyme adduct to form a "cleavable complex." Preclinical experiments using Western blot analyses have shown cleavable complex formation to be the key intermediate step in topo I inhibition. In this series of experiments, it was our goal to convert this laboratory technique into a useful clinical assay, allowing measurement of the target enzyme and detection of the key intermediate in clinical specimens taken from patients being treated with the topo I inhibitor topotecan. Because available antibodies were not sufficiently sensitive at the start of this project, we identified a highly specific human SCL-70 antibody from a patient with scleroderma, which allowed quantitative determination of topo I copy number in HeLa and HT-29 cell lines. Additional refinements of the Western blot technique were accomplished to improve signal:noise ratio. In surgical tumor specimens, we found the median topo I level to be 30.1 x 10(5) copies/cell for gastric adenocarcinomas, compared to 18.4 x 10(5) copies/cell for normal gastric mucosae in the same samples. For lung adenocarcinoma, the median protein level was 21.5 x 10(5) copies/cell, compared with the normal tissue counterpart protein level of 12.7 x 10(5) copies/cell. The median tumor:normal ratios from paired samples of these tumor types were 1.51 and 1.84, respectively. As part of a Phase II study evaluating the efficacy of topotecan (1.5-2.0 mg/m2 daily for 5 days) in upper gastrointestinal malignancies, we obtained tumor and normal mucosa biopsies in 11 patients with gastric or esophageal cancer, 30 min after administration on day 4 or 5. Three patients with gastric adenocarcinoma had stable disease as their best response, with the remainder of patients progressing. Improvement in Western blotting methodology allowed the quantitation of topo I levels in these gastric and esophageal cancer biopsies, which could be augmented by brief heating to release complexed topo I. We were also able to directly visualize high molecular weight topo I-containing bands, which were shown to be cleavable complexes by heat reversal, with restoration of the topo I Mr 100,000 band. Using this heat reversal technique, we determined the presence of cleavable complex in a total of 7 of 11 patient biopsy samples (5 tumors and 2 normal mucosae). In patients treated with topotecan on this dose and schedule, we determined that a median of 73% of the total tumor topo I was involved in cleavable complex (range, 18.3-91%). The intensity of the Mr 100,000 topo I band in biopsy specimens of patients receiving topotecan represented "free" or noncomplexed topo I. The median copy number for the residual, noncomplexed topo I (n = 11) was 7.36 x 10(5) copies/cell, significantly less than the median of 30.1 x 10(5) copies/cell for random tumor specimens from patients with gastric adenocarcinomas (P < 0.001). Pharmacodynamic analysis demonstrated a negative correlation between the noncomplexed topo I copy number and topotecan area under the curve (Spearman rank test: r(s) = -0.81, P = 0.003). Nonlinear regression analyses of these data were best fit with an inhibitory maximum effect model, yielding parameter estimates for Emax and EC50 of 29.3 x 10(5) copies/cell (coefficient of variation = 22%) and 43.1 ng x h/ml (coefficient of variation = 27%), respectively. Through a series of careful modifications and refinements, we have improved the Western blot assay for topo I for use in clinical monitoring. We have demonstrated the ability to directly visualize cleavable complex in patients being treated with topo I inhibitor therapy and have directly quantitated free topo I, as well as the key topo I intermediate (cleavable complex), in biopsy specimens obtained from pat
Adenoma, Islet Cell↗
Crithidia fasciculata induces encystation of Entamoeba invadens in a galactose-dependent manner.
The ability of the flagellate Crithidia fasciculata to induce encystation of the reptile pathogen, Entamoeba invadens, was studied in vitro. A specific ratio of flagellate to amoeba was required; both live and heat-killed C. fasciculata induced amoebic encystation. The interaction between the Crithidia and Entamoeba cells was found to be galactose-mediated because the addition of galactose to the culture medium, or the pretreatment of the flagellate with galactosidase, eliminated its ability to induce encystation. Galactose was also found to prevent the amoeba amoeba aggregation that normally occurs in axenic cultures of encystation-induced E. invadens. Both galactose and glcNAc completely inhibited cyst formation of these induced cultures, although the latter sugar did not prevent cell aggregation. These results indicate that a galactose-mediated interaction between E. invadens cells is an early step in the in vitro encystation pathway.
Animals↗
Chemotherapeutic activity of synthetic antimicrobial peptides: correlation between chemotherapeutic activity and neutrophil-activating activity.
The chemotherapeutic activity of three synthetic antibacterial peptides was investigated. KLKLLLLLKLK-NH2 and its D-enantiomer showed significant chemotherapeutic activity in MRSA-infected mice, whereas KLKLLLKLK-NH2, which showed the highest antibacterial activity among them in vitro, was found to have almost no ability to prevent MRSA infection. These results suggest that the antibacterial activity of peptides assessed in vitro does not necessarily correlate with their chemotherapeutic activity. We found that KLKLLLLLKLK-NH2 and its D-enantiomer, but not KLKLLLKLK-NH2, have the ability to activate human neutrophils to produce superoxide, suggesting that the prevention of MRSA infection by these peptides is not simply due to their direct bactericidal activity but to augmentation of the systemic defense mechanism mediated by neutrophils.
Animals↗
Differential effects of aging on NADPH-diaphorase and VIP neurons in cerebral cortex of rats.
Age-related changes of NADPH-diaphorase (NADPH-d) and vasoactive intestinal polypeptide (VIP) were examined in the rat brain. Aged (24 months) rats showed a significant decrease in the number of VIP-immunoreactive (IR) neurons in the cerebral cortex when compared with control (4 months) rats. However, the number of NADPH-d-positive neurons was not significantly different in the two groups. Quantitative analysis of cell areas revealed a significant shrinkage of VIP-IR neurons in the aged group, whereas no further cell shrinkage was noted for NADPH-d-positive neurons compared with the control group. These morphometric results demonstrate that NADPH-d-containing neurons are more resistant to aging than the VIP-IR neurons in the cerebral cortex of rats.
Aging↗
Distributions of single neurons related to body parts in the lateral striatum of the rat.
Single unit recordings in awake, unrestrained rats confirmed and extended previous findings regarding the functional organization of the lateral striatum. In individual electrode tracks, clusters of neurons related functionally to an individual body part were interspersed with clusters related to other body parts. The overlapping distributions of these neurons were arranged somatotopically in the dorsal-ventral dimension. The distribution of hind limb neurons was most dorsal and showed no overlap with the distribution of neurons related to oral sensorimotor activity. Oral representation was most ventral of all body parts and extended to the ventral boundary of the lateral striatum. Representations of other body parts overlapped with that of the hind limb dorsally but differed primarily in the degree to which they extended ventrally. Forelimb representation extended farther ventrally than that of the hind limb, but did not extend as far ventrally as that of the neck. Despite substantial overlap in the dorsal-to-ventral order of hind limb-forelimb-neck-face representations, single neurons showed no evidence of overlap, or convergence, of body parts. These data provide a more complete description of the dorsal-ventral somatotopy in the lateral striatum of the rat, which as shown previously, extends throughout the medial-lateral, and much of the anterior-posterior dimensions of the lateral striatum.
Animals↗
Activation of Stat1 by mutant fibroblast growth-factor receptor in thanatophoric dysplasia type II dwarfism.
The achondroplasia class of chondrodysplasias comprises the most common genetic forms of dwarfism in humans and includes achondroplasia, hypochondroplasia and thanatophoric dysplasia types I and II (TDI and TDII), which are caused by different mutations in a fibroblast growth-factor receptor FGFR3 (ref. 1). The molecular mechanism and the mediators of these FGFR3-related growth abnormalities are not known. Here we show that mutant TDII FGFR3 has a constitutive tyrosine kinase activity which can specifically activate the transcription factor Stat1 (for signal transducer and activator of transcription). Furthermore, expression of TDII FGFR3 induced nuclear translocation of Stat1, expression of the cell-cycle inhibitor p21(WAF1/CIP1), and growth arrest of the cell. Thus, TDII FGFR3 may use Stat1 as a mediator of growth retardation in bone development. Consistent with this, Stat1 activation and increased p21(WAF1/CIP1) expression was found in the cartilage cells from the TDII fetus, but not in those from the normal fetus. Thus, abnormal STAT activation and p21(WAF1/CIP1) expression by the TDII mutant receptor may be responsible for this FGFR3-related bone disease.
Animals↗
Phase I/II trial of low dose cyclosporin A with EP for advanced non-small cell lung cancer.
We and others have shown that cyclosporin A (CsA) reverses resistance to etoposide (E) and cis-platinum (P) in vitro and in vivo. To assess the clinical relevance of combined therapy, we studied CsA with EP in patients with advanced non-small cell lung cancer in a phase I/II clinical trial in a University setting. Patients were treated between July 1989 and June 1994 and included 10 females and 34 males with a median age of 61 years and a mean Karnofsky performance status of 80. CsA was given at escalating doses of 1-6 mg/kg per day on days 1-4 of each 21 day cycle with cis-platinum 25 mg/m2 per day and etoposide 100 mg/m2 per days on days 1-3. Response was assessed after each 2 cycles by measuring index lesions. A total of 44 patients received 133 cycles, 22.7% of patients had a partial response and 36.4% had stable disease with 8% 2-year survival. Patients receiving 1-2 mg/kg CsA had a PR rate of 37.5 and 50% SD compared to 19.4 and 33.3% for doses of 3 mg/kg or more. Although no conclusions should be drawn from this small study, the Kaplan-Meier survival curves were statistically significant different for these two groups by the log-rank test (P = 0.047). The 2-year survival of the former group was 25% compared to 4% for the latter. In light of the potential importance of immunomodulation in cancer control, it seems prudent to balance the effects of CsA on P-glycoprotein and other drug resistance pumps against its dose-dependent immunosuppressive activity. Further studies are needed to validate the activity of low dose CsA in combination with standard chemotherapy for lung cancer.
Adult↗
Quantitative study of the short range order in B2O3 and B2S3 by MAS and two-dimensional triple-quantum MAS 11B NMR.
Two-dimensional multiple-quantum magic angle spinning (MQMAS) NMR and MAS NMR of 11B at various magnetic fields, were applied to elucidate the structure of vitreous (glassy) boron trioxide (v-B2O3), vitreous boron trisulfide (v-B2S3) and crystalline boron trisulfide (c-B2S3). These techniques, when combined with computer simulations of the resulting spectra, provide the isotropic chemical shifts and the quadrupole parameters, as well as a quantitative measure of the intensities of various boron resonances. The MAS NMR of v-B2O3 produced overlapping anisotropic lineshapes corresponding to the -1/2<-->1/2 transition in two distinct types of BO3 units with 3(+/-0.08):] intensity ratio. A combination of MAS and the multiple-quantum method resulted in a better resolved, isotropic 11B spectrum of v-B2O3. A remarkable enhancement of resolution of the MQMAS NMR proved instrumental in finding and identifying various impurities present in v-B2S3 and c-B2S3. In addition to the resonances from boron in two types of BS3 groups, four other structural units, BOS2, BO2S, BO3 and BS4, were elucidated from the spectra of vitreous and crystalline samples. The effects of various experimental parameters, such as the magnitude of the B0 and B1 fields, on the resolution of the MAS and MQMAS techniques are also shown.
Algorithms↗
Posttrauma thromboembolism prophylaxis.
PURPOSE: The need to study methods of thromboembolism prophylaxis in high-risk trauma patients is well established. The purpose of this study was to evaluate the feasibility of a proposed study design, including current methods of prophylaxis, performance of a risk assessment profile scale, and the use of serial color-flow duplex studies in detecting deep venous thrombosis (DVT). METHODS: Patients were enrolled into the study, stratified as to their ability to receive anticoagulation and randomized to low-dose unfractionated heparin, low molecular weight heparin, pneumatic compression devices, or foot pumps with or without vena caval filters. Serial ultrasound scans were performed at designated intervals for 4 weeks. Pulmonary angiograms were obtained for clinical signs or symptoms of pulmonary embolism. RESULTS: Fifty-three patients, 32 male and 21 female patients with a mean age of 44 years, completed the study. The incidence of DVT was 43% (23 of 53 patients) and significantly higher in older patients. There were no pulmonary embolisms. Color-flow duplex proved to be a sensitive method for detecting both proximal and distal thrombi. The risk assessment profile for thromboembolism (RAPT) scale identified a group of patients with a high incidence of DVT. However, the occurrence of DVT was not correlated with the magnitude of the RAPT score. CONCLUSION: The ability to identify a population with a high incidence of thromboembolism by using the RAPT score to detect asymptomatic DVT, and the suggested advantage of low molecular weight heparin, all support the need for an appropriately powered randomized clinical trial.
Adult↗
Percutaneous radiofrequency lumbar facet rhizotomy in mechanical low back pain syndrome.
During the period from March 1992 to June 1996, we performed percutaneous radiofrequency (RF) facet rhizotomy in 324 patients with low back pain. Employing the lesion generator, we coagulated branches of the zygapophyseal nerve to treat low back pain. The follow-up period was 6-51 months (average: 22.5 months). There were no complications during the procedure and the follow-up period and no poor results were observed. Two-hundred and thirty-one patients (103 females and 128 males) had mechanical low back pain syndrome and showed marked improvement of pain after the procedure, including 29 cases with previous spinal surgery. We concluded that percutaneous RF facet rhizotomy is a safe and effective procedure for low back pain patients, especially for those with mechanical low back pain syndrome.
Electrocoagulation↗
Toll, a muscle cell surface molecule, locally inhibits synaptic initiation of the RP3 motoneuron growth cone in Drosophila.
Toll, a transmembrane molecule with extracellular leucine-rich repeats, is dynamically expressed by the Drosophila embryonic musculature. Growth cones of RP3 and other motoneurons normally grow past Toll-positive muscle cells and innervate more distal muscle cells, which have down-regulated their Toll expression. In this study, we show that reciprocal genetic manipulations of Toll proteins can produce reciprocal RP3 phenotypes. In Toll null mutants, the RP3 growth cone sometimes innervates incorrect muscle cells, including those that are normally Toll-positive. In contrast, heterochronic misexpression of Toll in the musculature leads to the same growth cone reaching its correct target region but delaying synaptic initiation. We propose that Toll acts locally to inhibit synaptogenesis of specific motoneuron growth cones and that both temporal and spatial control of Toll expression is crucial for its role in development.
Animals↗
Atomic structure of monatomic SB steps on clean Si(001) and Ni-contaminated Si(001).
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Journal Article↗