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Biomedical subjects

J Cho

Publications and source records attributed to J Cho.

At least 91 records · Page 5Linked to original sources

Tachycitin, a small granular component in horseshoe crab hemocytes, is an antimicrobial protein with chitin-binding activity.

Small granules of horseshoe crab hemocytes contain two known major antimicrobial substances, tachyplesin and big defensin (S5), and at least five protein components (S1 to S6), with unknown functions. In the present study, we examined the biological properties and primary structure of a small granular component S2, named tachycitin. This component was purified from the acid extract of hemocyte debris by two steps of chromatography. The purified tachycitin was a single chain protein with an apparent M(r) = 8,500 on Tricine-SDS-polyacrylamide gel electrophoresis. Ultracentrifugation analysis revealed tachycitin to be present in monomer form in solution. Tachycitin inhibited the growth of both Gram-negative and -positive bacteria, and fungi, with a bacterial agglutinating property. Moreover, tachycitin and big defensin acted synergistically in antimicrobial activities. The amino acid sequence and intrachain disulfide bonds of tachycitin were determined by amino acid and sequence analyses of peptides produced by enzymatic cleavages. The mature tachycitin consisted of 73 amino acid residues containing five disulfide bonds with no N-linked sugar. A cDNA coding for tachycitin was isolated from a hemocyte cDNA library. The open reading frame coded for an NH2-terminal signal sequence followed by the mature peptide and an extension sequence of -Gly-Arg-Lys at the COOH-terminus, which is a putative amidating signal. The COOH-terminal threonine amide released after digestion of tachycitin with lysylendopeptidase was identified. The NH2-terminal 28 residues of tachycitin shows sequence homology to a part of chitin-binding regions found in antifungal chitin-binding peptides, chitin-binding lectins, and chitinases, all of which have been isolated from plants. Tachycitin showed a specific binding to chitin but did not bind with the polysaccharides cellulose, mannan, xylan, and laminarin. Tachycitin may represent a new class of chitin-binding protein family in animals.

Amino Acid Sequence↗

Cyclic polyamides for recognition in the minor groove of DNA.

Small molecules that specifically bind with high affinity to any designated DNA sequence in the human genome would be useful tools in molecular biology and potentially in human medicine. Simple rules have been developed to rationally alter the sequence specificity of minor groove-binding polyamides containing N-methylimidazole and N-methylpyrrole amino acids. Crescent-shaped polyamides bind as antiparallel dimers with each polyamide making specific contacts with each strand on the floor of the minor groove. Cyclic polyamides have now been synthesized that bind designated DNA sequences at subnanomolar concentrations.

Amides↗

Collateral sensitivity to radiation and cis-platinum in a multidrug-resistant human leukemia cell line.

Although collateral sensitivity to gamma radiation has previously been described in multidrug-resistant tumor cell lines, we describe here a multidrug-resistant human T-cell acute lymphatic leukemia cell line, L100, which displayed increased sensitivity to both gamma radiation and cis-platinum. Cis-platinum cytotoxicity of parental L0 cells and L100 cells was enhanced, whereas radiation sensitivity of L0 and L100 cells was unaltered by glutathione depletion. These results indicate that disparate mechanisms are operative in the collateral sensitivity of L100 cells to gamma radiation and cis-platinum.

Antineoplastic Agents↗

A novel big defensin identified in horseshoe crab hemocytes: isolation, amino acid sequence, and antibacterial activity.

Hemocytes of the horseshoe crab (limulus) contain a family of arthropodous peptide antibiotics, termed the tachyplesin family, and antibacterial protein, called anti-LPS factor, of which the former is located in the small (S) granules and the latter in the large (L) granules of the hemocytes. In our ongoing studies on granular components, we have identified here a novel defensin-like substance present in both L- and S-granules. This substance strongly inhibits the growth of Gram-negative and -positive bacteria, and fungi, such as Candida albicans. The isolated substance, tentatively termed "big defensin," consists of 79 amino acid residues, of which the COOH-terminal 37 residues have a sequence similar to those of mammalian neutrophil-derived defensins, especially rat defensin. Characterization of the disulfide motif in big defensin indicated that the disulfide array is identical to that of beta-defensins from bovine neutrophils. One clear structural difference is that the limulus hemocyte-derived big defensin has an extension of the NH2-terminal hydrophobic sequence with 35 amino acid residues followed by the COOH-terminal cationic defensin portion. This amphipathic nature of big defensin seems likely to be associated with its potent antibacterial activity. Furthermore, antibacterial activities of the NH2-terminal hydrophobic region and the COOH-terminal defensin portion separated by tryptic digestion are significantly different: the former displays a more potent activity against Gram-positive bacteria, whereas the latter is more potent against Gram-negative bacteria. Big defensin, therefore, may prove to represent a new class of defensin family possessing two functional domains with different antimicrobial activities.

Amino Acid Sequence↗

Complications following Gamma Knife radiosurgery.

Between May 1992 and February 1994, 213 lesions in 183 consecutive patients were treated with Gamma Knife radiosurgery at Severance Hospital, Yonsei University, Seoul, Korea. During this period, we experienced 2 deaths, 1 directly and another indirectly related to irradiation. Nonfatal complications included 1 tumor bleeding, and 4 ventriculoperitoneal shunts had to be inserted due to aggravation of preexisting hydrocephalus. Radiation-induced imaging changes developed in 23.6% of the cases followed up for more than 6 months. Among 24 lesions of 8 cavernous hemangiomas, all 4 cases with lesions larger than 1.5 cm3 developed imaging changes.

Dose-Response Relationship, Radiation↗

Availability of discographic computed tomography in automated percutaneous lumbar discectomy.

Automated percutaneous lumbar discectomy (APLD) has been developed since 1984 when Gary Onik first attempted it. This procedure has many advantages and has been used widely in the treatment of protruded disc diseases. The success rate of APLD by authors from March 1988 to February 1993 when the discographic computed tomography (CT) had not been performed was 74%. In evaluating lumbar disc diseases, we have used discographic CT. According to the patterns of dye distribution in the disc, two different types of protrusion can be distinguished: broad dye base protrusion and narrow dye base protrusion. From April 1993 to July 1994, 52 patients with protruded disc diseases were performed discographic CT. 23 Patients had narrow dye base protrusion and 29 patients had broad dye base protrusion. 29 patients with a broad dye base on discographic CT were treated with APLD and evaluated. The success rate in these patients was 93% by Macnab's criteria. Thus, we suggest that it is mandatory to apply discographic CT to increase the success rate of APLD in patients with protruded disc diseases.

Adolescent↗

Cell cycle progression in the developing Drosophila eye: roughex encodes a novel protein required for the establishment of G1.

The onset of pattern formation in the developing Drosophila eye is marked by the simultaneous synchronization of all cells in the G1 phase of the cell cycle. These cells will then either commit to another round of cell division or differentiate into neurons. Although cell cycle synchronization occurs in roughex (rux) mutants, cells circumvent G1 and all cells enter S phase, including cells that would normally differentiate. This leads to defects in early steps of pattern formation and cell fate determination. rux is suppressed by mutations in genes that promote cell cycle progression (i.e., cyclin A and string) and enhanced by mutations in genes that promote differentiation (i.e., Ras1 and Star). rux encodes a novel protein of 335 amino acids. We propose that rux functions as a negative regulator of G1 progression in the developing eye.

Amino Acid Sequence↗

Loss of developing cholinergic basal forebrain neurons following excitotoxic lesions of the hippocampus: rescue by neurotrophins.

Previous studies have demonstrated that the viability of developing cholinergic basal forebrain neurons is dependent upon the integrity of neurotrophin-secreting target cells. In the present study, we examined whether infusions of nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) could prevent the loss of cholinergic septal/diagonal band neurons following excitotoxic lesions of their target neurons within the hippocampus. Postnatal Day 10 rat pups received unilateral intrahippocampal injections of ibotenic acid. Rats then received intracerebroventricular (icv) injections of nerve growth factor (30 micrograms/injection), brain-derived neurotrophic factor (60 micrograms/injection), or saline immediately following the lesion and continuing every third day for 27 days. Both saline- and BNDF-treated rats displayed a significant loss of septal/diagonal band neurons expressing the protein and mRNA for choline acetyltransferase (ChAT) and p75 low-affinity nerve growth factor receptor ipsilateral to the lesion. The magnitude of this loss was significantly attenuated in BNDF-treated rats. Many remaining neurons were atrophic with stunted dendritic processes. In contrast, NGF treatment completely rescued these cells and prevented the shrinkage of remaining cholinergic septal neurons. In addition, both NGF and BDNF induced a sprouting of cholinergic processes within the residual hippocampal remnant ipsilateral to the infusions. The present study demonstrates that icv injections of NGF, and to a lesser extent BDNF, prevent the loss of developing basal forebrain neurons which occurs following removal of normal target cells. Diffusion studies revealed relatively poor penetration of BDNF into brain parenchyma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Representation of the body in the lateral striatum of the freely moving rat: single neurons related to licking.

This study examined the relationship of single-neuron activity (n = 739), recorded from the lateral striatum of freely moving rats, to oral movements involved in licking single drops of liquid. Certain neurons (n = 74) fired specifically in relation to licking. Their firing rates increased during licking, but remained near zero in the absence of licking, throughout a full sensorimotor examination of the remainder of the orofacial area and all other body parts. Another category of neurons (n = 17) fired during licking but also fired in the absence of licking, during one or more other orofacial sensorimotor function(s). Lick-related neurons were located in the lateral striatum, throughout the entire anterior-posterior range studied (from +1.5 to -1.5 mm anterior-posterior, A-P, bregma = 0). Summed over the full A-P range, they were located significantly ventral to representations of the trunk and limbs. These findings extend the characterization of the somatotopic organization exhibited by lateral striatal neurons in the rat, to include representation of oral functions, consistent with converging evidence regarding the functional organization of the striatum.

Animals↗

Long-term follow-up results of stereotactic adrenal medullary transplantation in Parkinson's disease.

Stereotactic adrenal medullary transplantation into the striatum was performed in 5 patients with severe Parkinson's disease. Four patients had previously been treated with thalamotomies and all were on L-dopa therapy with significant side effects. All 5 patients had shown marked disability before the procedure. Autologous adrenal medullary tissue was sliced into 20-30 fragments and transplanted into two sites of the caudate nucleus, one at the ventricular surface and the other in the head of the nucleus. The cases were followed for 4-5 years (mean 4.5 years), except for 1 patient who died of unrelated causes 22 months after the procedure. Initial bilateral symptom improvement was observed in all cases for 9-21 months (mean 15.2 months) after transplantation without L-dopa therapy. Later, these improvements progressively deteriorated. L-dopa therapy had to be resumed for all. MRI on the long-term follow-up showed the transplanted tissue as a low signal intensity area surrounded by high intensity spots in T1- and T2-weighted images. Compared to previous MR studies, the transplanted tissue was shrunken and presumed nonviable.

Adrenal Medulla↗

Extrafollicular reticulum cells in pathologic lymph nodes.

Extrafollicular reticulum cells in lymph nodes are heterogeneous. They express cytokeratins, desmin, and/or vimentin as their intermediate filament profile. Using those markers, we undertook an immunohistochemical study of human lymph nodes under various pathologic conditions. Samples included 15 simple reactive lymph nodes, 7 follicular hyperplasia, 1 necrotizing lymphadenitis, 4 tuberculous lymphadenitis, 13 malignant lymphoma (9 non-Hodgkin's and 4 Hodgkin's lymphomas), and 11 metastatic adenocarcinoma. In lymph nodes with follicular hyperplasia, cytokeratin and/or desmin expressing reticulum cells displayed a characteristic dendritic meshwork in the subcapsular, perisinusoidal, and paracortical regions. In other forms reactive lymph nodes, they were similarly distributed but were less prominent. By SDS-PAGE and immunoblotting, cytokeratin polypeptides were identified. In necrotizing lymphadenitis, they were increased and the pattern of distribution was disturbed. In tuberculous lymphadenitis, they were also increased and located at nongranulomatous as well as in perigranulomatous areas. In lymphomas the reticular meshwork was entirely obliterated. Cytokeratin or desmin expressing reticulum cells were rarely seen within tumors. The reticular meshwork was also obliterated in metastatic carcinoma. However, the meshwork was maintained in uninvolved areas. In conclusion, extrafollicular reticulum cells displayed characteristic patterns of distribution under various pathologic conditions, and may be implicated in the pathogenesis of those pathologic conditions in human lymph nodes.

Antibodies, Monoclonal↗

Endodermal sinus tumor: immunophenotypic expression of a carcinoma.

A series of five endodermal sinus tumors was studied for their cytoskeletal and other phenotypic markers. They included 2 ovarian, 2 testicular, and 1 inguinal tumors. The cytoskeletal expression was also studied by gel electrophoresis and immunoblotting. Every tumor was diffusely and strongly immunostained for cytokeratin. By SDS-PAGE and immunoblotting, cytokeratins 8 & 18 were detected. Vimentin was focally coexpressed in 4 cases. The stroma was diffusely immunostained for vimentin. None of them expressed desmin, neurofilament, or glial filament protein. Desmoplakin was expressed only in one ovarian tumor. Alpha-fetoprotein and S-100 protein were also diffusely positive among the neoplastic cells; intracytoplasmic globules were especially strongly immunostained. These findings suggest that endodermal sinus tumors represent a group of pure malignant epithelial neoplasms, and may be regarded as primitive carcinomas.

Adult↗

Cyclosporin A potentiation of VP-16: production of long-term survival in murine acute lymphatic leukemia.

Our prior in vitro studies on the correction of multidrug resistance by cyclosporin A (CsA) prompted us to investigate the effect of CsA and VP-16 in vivo. CsA given simultaneously at 2 or 10 mg/kg with VP-16 to BDF/1 mice bearing parental drug-sensitive P388 or L1210 lymphatic leukemia produced a 100% increase in survival as compared with VP-16 treatment alone. CsA-containing regimens also promoted 60-day survival in a significant number of P388 or L1210 leukemia-bearing mice as compared with animals receiving VP-16 in the absence of CsA (P < 0.02 and P < 0.001, respectively). CsA enhancement of the survival of mice bearing these lymphatic leukemias is restricted to VP-16, since the addition of CsA to therapeutic agents such as vincristine, daunorubicin, methotrexate, or cisplatin had no effect on survival.

Animals↗

Phase II trial of 5-fluorouracil, high-dose leucovorin calcium, and dipyridamole in advanced prostate cancer.

To examine the effect of altering intracellular folate pools on the efficacy of 5-fluorouracil (FUra) in the treatment of advanced prostate cancer, we performed a phase II trial of FUra (300-370 mg m-2 day-1 x 5 as an i.v. bolus) combined with high-dose folinic acid (500 mg m-2 day-1 x 5.5 days by continuous i.v. infusion) and dipyridamole (75 mg p.o. every 6 h x 5.5 days) administered on a 28-day schedule in patients with stage D2 disease. A group of 13 patients have been treated. The median age was 68 years (range 48-78 years); the performance status ranged from 50% to 90%. Among 12 evaluable patients, there were no objective responders; the median time to progression was 1.9 months. Median survival after entry on this trial was 8.6 months. Treatment with FUra, high-dose folinic acid and dipyridamole was well tolerated. Only one episode each of grade 3 leukopenia, granulocytopenia, and thrombocytopenia was observed. These results suggest that, despite previous trials demonstrating activity for FUra in stage D2 prostate cancer, this disease may be relatively resistant to fluoropyrimidines and, thus, less amenable to biochemical modulation with high-dose folinic acid and dipyridamole.

Aged↗

Kaposi's sarcoma.

In the era before the acquired immunodeficiency syndrome, Kaposi's sarcoma was a rare cutaneous event. Most reported cases usually originated from one of two geographic regions, an induced immunosuppressed state, or sporadically with various neoplasms that have been known to cause immunosuppression. Since the first cases described with acquired immunodeficiency syndrome in 1981 from New York and San Francisco, this uncommon disorder has had an increased incidence that crosses geographic boundaries. This article describes the current understanding of the pathogenesis of Kaposi's sarcoma and treatments used to ameliorate this disorder.

Acquired Immunodeficiency Syndrome↗