Biomedical subjects

L Chu

Publications and source records attributed to L Chu.

At least 55 records · Page 3Linked to original sources

PubMed1995

Synchrony in adolescence.

When the social environment does not change to meet an adolescent's needs for independence, self-determination, and participation in decision making, a developmental mismatch may occur. The interactive model of synchrony studied extensively in early parent-child relationships has suggested that a mutual and responsive interaction between the child and the caretaker is essential to the child's development of secure attachment, sense of autonomy, and social competence. A life-span view of development allows the concept of synchrony to be extended to the stage of adolescence, providing clues to how developmental mismatches occur between adolescents, teachers, and parents as well as useful guidelines for the prevention and remediation of such mismatches.

Adolescent↗

PubMed1995

Oral vinorelbine (Navelbine) in the treatment of advanced breast cancer.

Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) has been formulated as a liquid-filled, soft gelatin capsule. Pharmacokinetic studies of this agent indicate that it has a large volume of distribution, a long terminal half-life, and a high clearance rate. The pharmacokinetics of vinorelbine are similar whether the drug is administered orally or intravenously. Oral vinorelbine has a low bioavailability, which may be due to a high first-pass effect. Preliminary results from two multicenter phase II trials of oral vinorelbine in patients with advanced breast cancer are presented. In one study of 98 advanced breast cancer patients aged 65 years and older with limited prior therapy, the response rate of oral vinorelbine was 24% (complete response, 5%; partial response, 19%). In a study of 131 heavily pretreated patients with advanced breast cancer, the response rate of oral vinorelbine was 11% (complete response, 0%; partial response, 11%). In both studies, oral vinorelbine was generally well tolerated. As with intravenous administration, neutropenia is common and neuropathy is infrequent. In contrast to intravenous administration, nausea, vomiting, and diarrhea are common. Based on these preliminary results, further clinical investigation of oral vinorelbine is warranted.

Administration, Oral↗

PubMed1994

Neonatal laryngoceles. A cause for airway obstruction.

The neonatal laryngocele is a congenital pathologic entity originating in the saccule of the laryngeal ventricle. This entity may present as an uncommon cause of neonatal airway obstruction. We present two cases of this condition and the management undertaken. Both patients demonstrated significant airway distress. Evaluation of each patient included either plain x-ray films of the neck, ultrasound, or computed tomography of the neck. A cystic mass, containing air and fluid, was identified causing external compression of the airway in each case. Surgical intervention required airway endoscopy and an external approach to excise the mass. Tracheotomy was avoided in both cases; however, one infant required further surgery for laryngomalacia. Both children have done well in follow-up.

Airway Obstruction↗

PubMed1994

Characterization of hemolysis and hemoxidation activities by Treponema denticola.

This study determined the presence of two hemolytic activities in the oral treponeme, Treponema denticola, strains ATCC 35404 (TD-4), ATCC 33520, GM-1, and MS25. These activities, referred to as hemolytic and hemoxidative (HeA, HeO, respectively), were found to be both secreted into the extracellular environment, and cell associated. The extracellular activity was associated with small molecules with relative molecular weights of < 1000 Da, and its activity was cysteine independent; the cell-associated HeA and HeO activities were associated with a molecular weight fraction > 10 kDa, and were cysteine dependent. The HeO activity of the fractionated material observed was due to the oxidation of hemoglobin to methemoglobin, and preceded the HeA lysis of the RBCs by approximately 2 h. Heating at 80 degrees C and treatment with proteinase K resulted in the complete destruction of these activities in the fraction > 10 kDa, while lipase at high concentration (800 micrograms/ml) reduced the HeA and HeO activities in the extracellular fraction by approximately 50%. Proteinase inhibitors had a variable effect on HeA and HeO activities in both extracellular and cell-associated fractions. Scanning and transmission electron microscopy revealed a progressive destruction of the RBC membrane, with membrane protrusions formed early in the interaction, which progressed to irregular holes in the membrane, and the complete loss of membrane integrity.

Erythrocytes↗

PubMed1994

Purification and characterization of a 45 kDa hemolysin from Treponema denticola ATCC 35404.

A 45 kDa polypeptide capable of erythrocyte (RBC) lysis and hemoglobin oxidation was isolated from Treponema denticola, ATCC 35404 (TD-4) after sequential ammonium sulfate (2.8-3.6 M) precipitation and preparative electrophoresis. The purified polypeptide produced a single protein band on PAGE at a relative molecular weight of 45 kDa in the presence and absence of SDS. The polypeptide was sensitive to proteinase K and pronase, and heating at 80 degrees C. The protease inhibitors, PMSF, TLCK and benzamidine had no inhibitory affect on activity. It was non heat-modifiable, and lost all hemolytic and hemoxidative function in SDS. Cysteine and other sulfhydryl-containing compounds were required for hemolytic and hemoxidative activities. The isoelectric point of the polypeptide was 5.3 and N'-terminal sequence analysis indicated it to belong to a new, so far undescribed group of peptides possessing hemoxidation and hemolytic activities. Functionally, it was capable of rapid hemoxidation of sheep and human erythrocytes (hemoglobin to methemoglobin) coupled to erythrocyte lysis, or hemolysis.

Amino Acid Sequence↗

PubMed1994

Effect of iron regulation on expression and hemin-binding function of outer-sheath proteins from Treponema denticola.

The effect of the iron-chelating compounds EDDA and BPD on polypeptide regulation in the putative oral pathogen Treponema denticola was studied. SDS-PAGE analysis of the T. denticola strains grown in the presence of EDDA or BPD, i.e. iron-limiting environmental conditions, revealed the expression of 44 and 43 kDa polypeptides in the outer sheath, a 73 kDa polypeptide in the cell membrane, and a 16 kDa polypeptide in the soluble cell fraction. The hemin-binding activity of purified outer sheaths from T. denticola TD-4 grown in the presence of 6.4 mM EDDA was significantly greater than that observed in control (absence of EDDA) outer sheaths. Both activities were inhibited by proteinase K. SDS-PAGE, LDS-PAGE and TMBZ staining revealed the 44 and 43 kDa outer-sheath polypeptides to be expressed by T. denticola strains GM-1. MS-25, ATCC 33520 and ATCC 33404 (TD-4), strains which possessed strong hemin-binding activity. The 44 kDa hemin-binding polypeptide was purified by 1% CHAPS solubilization, HPLC, and SDS-preparative electrophoresis. N'-terminal sequence analysis indicated the purified 44 kDa polypeptide to belong to a new, undescribed group of polypeptides possessing hemin-binding activity.

2,2'-Dipyridyl↗

PubMed1994

A treatment protocol for mandible fractures.

Mandibular fracture management has evolved over several decades, and controversies exist over ideal approaches for individual fractures. Treatment choices include closed versus open techniques, reduction methods and repair, and decision concerning intermaxillary fixation. Both the patient and the fracture characteristics have an impact on these choices. Patient factors include age, mandibular bone quality, dentition, patient reliability, and associated injuries. Fracture characteristics include favorability versus unfavorability, single versus multiple, location, and infection. This study was undertaken to develop and evaluate a management algorithm to determine the best treatment of mandible fractures. Sixty-seven patients were managed at the Grady Memorial Hospital otolaryngology service. Ages ranged from 3 to 68 years and included 55 male patients and 12 female patients. Forty-three patients had multiple fractures, while 24 had single fractures. Sixty-four patients were successfully managed and had normal function on follow-up examination. Eleven patients (16.4%) had complications. These included three infections, one malunion, two malocclusions, and five marginal nerve pareses. Multiple fractures did not have a higher incidence of complication. This protocol allows an orderly approach to the successful outcome of mandibular fractures.

Adolescent↗

PubMed1994

Analysis of changes in DNA sequence copy number by comparative genomic hybridization in archival paraffin-embedded tumor samples.

Analysis of previously unknown genetic aberrations in solid tumors has become possible through the use of comparative genomic hybridization (CGH), which is based on competitive binding of tumor and control DNA to normal metaphase chromosomes. CGH allows detection of DNA sequence copy number changes (deletions, gains, and amplifications) on a genome-wide scale in a single hybridization. We describe here an improved CGH technique, which enables reliable detection of copy number changes in archival formalin-fixed paraffin-embedded tumor samples. The technique includes a modified DNA extraction protocol, which produces high molecular weight DNA which is necessary for high quality CGH. The DNA extraction includes a 3-day digestion with proteinase K, which remarkably improves the yield of high molecular weight DNA. Labeling of the test DNA with a directly fluorescein-conjugated nucleotide (instead of biotin labeling) improved significantly the quality of hybridization. Using the paraffin-block technique, we could analyze 70 to 90% of paraffin blocks, including very old samples as well as samples taken at autopsy. CGH from paraffin blocks was highly concordant (95%) with analyses done from matched freshly frozen tumor samples (n = 5 sample pairs; kappa coefficient = 0.83). The method described here has wide applicability in tumor pathology, allowing large retrospective prognostic studies of genetic aberrations as well as studies on genetic pathogenesis of solid tumors, inasmuch as premalignant lesions and primary and metastatic tumors can be analyzed by using archival paraffin-embedded samples.

Chromosome Mapping↗

PubMed1993

Early expression of human J chain and mu chain gene in the fetal liver.

The expression of J chain and mu chain genes has been investigated during human fetal ontogeny by the polymerase chain reaction performed on liver sections. With this technique, we have been able to detect expression of J chain and mu chain in a single 6-10-microns-thick formalin-fixed paraffin-embedded section of fetal liver tissue. J chain expression reached a maximum at 16 weeks of gestation but was clearly detectable in the liver at the 6th week. Although not detectable at the 6th week, mu chain mRNA became readily detectable at 7 weeks of gestation. These results indicate that J chain expression precedes that of mu chain by at least one week. Therefore, our results imply that J chain is the first immunoglobulin-related polypeptide expressed during the embryogenesis and differentiation of B cells in the fetal liver.

Base Sequence↗

PubMed1993

Amelanotic melanoma of the oral cavity.

A case of amelanotic melanoma arising in the upper molar region, which was difficult to diagnose histologically, is reported. The patient was a 79-year-old woman, who complained of a painful swelling in the gingiva of the left upper molar region. Routine histological examination showed that the lesion was composed of diffusely scattered atypical cells with round, spindle-shaped and irregular nuclei and scanty fibrous connective tissue. A fascicular arrangement was often found in the lesion, and no cancer nests were observed. Immunohistochemical study demonstrated positive staining for S-100 protein in both the nuclei and cytoplasm of the tumor cells. Electron microscopic examination revealed that cell organelles were abundant, and an interrupted basal lamina was often found along the cell membrane. The preliminary diagnosis was a non-epithelial malignant tumor. After surgery, histological examination of metastases in lymph nodes from the submandibular region revealed that the tumor cells contained melanin pigment in the cytoplasm, as confirmed by Masson's melanin stain. The final pathological diagnosis was therefore amelanotic melanoma. Immunohistochemical staining for S-100 protein may be useful for differential diagnosis of amelanotic melanoma in conjunction with electron microscopic examination.

Aged↗

PubMed1993

Natural antibody against Thomsen-Friedenreich antigen in sera of patients with carcinomas and infectious diseases.

The levels of natural antibody against Thomsen-Friedenreich (TF) antigen in sera of patients with various cancers and infectious diseases were examined by an enzyme-linked immunosorbent assay (ELISA) and compared with those of healthy donors. The levels of antibody against TF antigen in sera of patients with adenocarcinomas such as gastric, pancreatic and colorectal cancers were lower than those of patients with hepatoma, pyelonephritis and pneumonia. These findings may reflect the expression of TF-antigen in adenocarcinoma tissues.

Antibodies, Neoplasm↗

PubMed1992

Regulation of the Staphylococcus aureus plasmid pI258 mercury resistance operon.

Experiments involving fusion between the Staphylococcus aureus plasmid pI258-encoded mer operon and the reporter gene beta-lactamase, mutational analysis, and trans-complementation studies have shown that the merR gene of pI258, which shows DNA sequence similarity with known merR genes from other bacteria, regulates the expression of the mer operon in vivo. The merR gene product is a trans-acting protein that activates mer operon transcription in the presence of the inducers Hg2+ and Cd2+. A glutathione-S-transferase-MerR fusion protein specifically bound and protected a 27-nucleotide operator sequence from DNase I digestion. This operator sequence is highly homologous with mer operator sequences of other known systems.

Bacterial Proteins↗

PubMed1991

Nucleotide sequence and expression of the algE gene involved in alginate biosynthesis by Pseudomonas aeruginosa.

Alginate (Alg), a random polymer of mannuronic acid and glucuronic acid residues, is synthesized and secreted by Pseudomonas aeruginosa primarily during its infection of the lungs of cystic fibrosis patients. The molecular biology and biochemistry of the enzymatic steps leading to the production of the Alg precursor GDP-mannuronic acid have been elucidated, but the mechanism of polymer formation and export of Alg are not understood. We report the nucleotide sequence of a 2.4-kb DNA fragment containing the algE gene, previously designated alg76, encoding the AlgE protein (Mr 54,361) that is believed to be involved in these late steps of Alg biosynthesis. Expression of algE appears to occur from its own promoter. The promoter region contains several direct and inverted repeat sequences and shares structural similarity with promoters of several other alg genes from P. aeruginosa. In addition, the AlgE protein was overproduced from the tac promoter in P. aeruginosa. N-terminal amino acid sequence analysis showed that the polypeptide contains a signal peptide which is cleaved to form the mature protein during AlgE export from the cell cytoplasm.

Alginates↗

PubMed1991

Antisera specific for rap 1 proteins distinguish between processed and nonprocessed rap 1b.

Polyclonal antisera were generated against synthetic peptides corresponding to distinct regions of the rap 1 protein sequences. A "rap 1-common" antiserum, prepared against an 18-amino acid segment of the rap 1a protein near the proposed GTP-binding region, reacted with both rap 1a and rap 1b recombinant proteins expressed in Escherichia coli and with two low molecular weight GTP-binding proteins of 22 and 24 kDa in unstimulated human platelets. An antiserum raised against a carboxyl-terminal peptide of rap 1b containing the putative site of post-translational processing reacted strongly with bacterial-expressed recombinant rap 1b and with a 24-kDa GTP-binding protein in platelets, but not with recombinant rap 1a or a 22-kDa GTP-binding protein. The mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of this rap 1b immunoreactive protein coincided with that of bacterial-expressed rap 1b and not with the faster migrating form of rap 1b that incorporates radioactivity from [3H]mevalonic acid in the insect/baculovirus system. This suggests that our rap 1b-specific antiserum recognizes only one form of rap 1b, that which has not undergone carboxyl-terminal post-translational processing.

Amino Acid Sequence↗

PubMed1991

Alginate synthesis by Pseudomonas aeruginosa: a key pathogenic factor in chronic pulmonary infections of cystic fibrosis patients.

Pulmonary infection by mucoid, alginate-producing Pseudomonas aeruginosa is the leading cause of mortality among patients suffering from cystic fibrosis. Alginate-producing P. aeruginosa is uniquely associated with the environment of the cystic fibrosis-affected lung, where alginate is believed to increase resistance to both the host immune system and antibiotic therapy. Recent evidence indicates that P. aeruginosa is most resistant to antibiotics when the infecting cells are present as a biofilm, as they appear to be in the lungs of cystic fibrosis patients. Inhibition of the protective alginate barrier with nontoxic compounds targeted against alginate biosynthetic and regulatory proteins may prove useful in eradicating P. aeruginosa from this environment. Our research has dealt with elucidating the biosynthetic pathway and regulatory mechanism(s) responsible for alginate synthesis by P. aeruginosa. This review summarizes reports on the role of alginate in cystic fibrosis-associated pulmonary infections caused by P. aeruginosa and provides details about the biosynthesis and regulation of this exopolysaccharide.

Alginates↗

PubMed1991

Hemolytic activity in the periodontopathogen Porphyromonas gingivalis: kinetics of enzyme release and localization.

Porphyromonas gingivalis W50, W83, A7A1-28, and ATCC 33277 were investigated for their abilities to lyse sheep, human, and rabbit erythrocytes. All of the P. gingivalis strains studied produced an active hemolytic activity during growth, with maximum activity occurring in late-exponential-early-stationary growth phase. The enzyme was cell bound and associated with the outer membrane. Fractionation of P. gingivalis W50 localized the putative hemolysin almost exclusively in the outer membrane fraction, with significant hemolytic activity concentrated in the outer membrane vesicles. Ca2+ and Mg2+ ions significantly increased the expression of hemolytic activity. Hemolytic activity was inhibited by proteinase K, trypsin, the proteinase inhibitors Na-P-tosyl-L-lysine chloromethyl ketone and benzamidine, the metabolic inhibitor M-chlorophenyl-hydrazone, and iodoacetate. KCN and sodium azide (NaN3) only partially inhibited P. gingivalis hemolytic activity, while antiserum to whole cells of each of the P. gingivalis strains had a significant inhibitory effect on hemolytic activity. The P. gingivalis W50 hemolysin was inhibited by cysteine, dithiothreitol, and glutathione at concentrations of at least 10 mM; at low concentrations (i.e., 2 mM), dithiothreitol did not completely inhibit hemolytic activity. Heating to temperatures above 55 degrees C resulted in an almost complete inhibition of hemolytic activity. The effect of heme limitation (i.e., iron) on hemolysin production indicated that either limitation or starvation for heme resulted in significantly increased hemolysin production compared with that of P. gingivalis grown in the presence of excess heme.

Animals↗

PubMed1990

Effects of MK-801 on glutamate-induced swelling of astrocytes in primary cell culture.

The effects of glutamate and its agonists and antagonists on the swelling of primary astrocytes were studied. Glutamate (Glu), aspartate (Asp), homocysteate (HCA), and quisqualate (Quis) at 1 mM concentration caused a significant increase in astrocytic swelling as measured by the 3-0-methyl-[14C]-glucose, whereas kainate (KA), N-methyl-D-aspartate (NMDA), and receptor antagonists 2-amino-5-phosphonovaleric acid (APV), 2-amino-7-phosphonohepatanoic acid (APH), and kynurenic acid (Kynu) were not effective. This glial swelling was time-dependent since 1-hr or greater incubations with Glu or its agonists were needed to produce such an effect. Preincubation of glutamate or NMDA receptor anatogonists including Kynu, APH, and APV failed to ameliorate the Glu effects. However, MK-801, a noncompetitive NMDA antagonist, when added to the Glu-incubated astrocytes significantly reduced Glu-induced astrocytic swelling. MK-801 was also effective in reducing the astrocytic swelling induced by agonists including Asp, Quis, and HCA, suggesting that those agonists may share similar mechanisms of Glu in inducing astrocytic swelling. Since the cultured astrocytes lack the NMDA receptors, our data suggest that the observed beneficial effects of MK-801 on excitotoxin-induced swelling of astrocytes may be mediated by mechanisms other than NMDA receptors.

Animals↗

PubMed1990

Mechanisms underlying glutamate-induced swelling of astrocytes in primary culture.

The effects of glutamate and its agonists and antagonists on the swelling of primary astrocytes were studied. Glutamate, aspartate, homocysteate, and quisqualate caused a significant increase in astrocytic swelling as measured by 3-0-methyl-[14C]-glucose uptake and by phase-contrast microscopic observations. N-methyl-D-aspartate and kainate were not effective, nor were the competitive NMDA receptor antagonists. Ketamine and MK-801, the non-competitive NMDA receptor antagonists protected the cultured astrocytes against glutamate-induced swelling. Moreover, Glu-induced astrocytic swelling was significantly reduced when sodium-ions were depleted from the culture medium. The sodium ion dependence of Glu-induced astrocytic swelling is rather specific, since depletion of Ca2+ or Mg2+ had no effect. Our data suggest that Na(+)-dependent, Glu-mediated cell swelling occurs in primary cell cultures of astrocytes.

Animals↗