Biomedical subjects

K Y Chien

Publications and source records attributed to K Y Chien.

At least 19 recordsLinked to original sources

PubMed2000

Binding of a de novo designed peptide to specific glycosaminoglycans.

The binding of glycosaminoglycans to a synthetic peptide (SKAQKAQAKQAKQAQKAQKAQAKQAKQW-CONH(2)), consisting of a hybrid consensus heparin binding sequence, is studied using circular dichroism, fluorescence anisotropy and nuclear magnetic resonance techniques. The results unveil certain novel features, most importantly, the peptide binds preferentially to iduronic acid containing glycosaminoglycans and the dissociation constant for the peptide-heparin complex was found to be 30 nM. Interestingly, higher order intermolecular association(s)/aggregation was not observed, especially at saturating concentrations of the ligand. The helical structure of the peptide backbone, induced upon binding to a particular glycosaminoglycan is directly related to their binding affinity. In our opinion, studies on such unconventional hybrid peptide sequences containing low density basic amino acid residues would lead to the design of sequence specific glycosaminoglycan binding peptides.

Amino Acid Sequence↗

PubMed1996

Conformational change and inactivation of membrane phospholipid-related activity of cardiotoxin V from Taiwan cobra venom at acidic pH.

The phospholipid binding activity of cardiotoxin V from Naja naja atra (CTX A5) was studied by use of Langmuir monolayers and found to exhibit pH-dependence in binding to phosphatidylcholine membrane with an apparent pKa around 6.0. Proton NMR investigation of the CTX A5 molecule in the presence of phosphatidylcholine micelles reveals a decrease in association of CTX A5 with membranes at low pH as a result of the protonation of His-4 near the membrane binding site of loop I region of CTX. The pH-dependent binding can be attributed mainly, but not solely, to the change in charge content of the CTX molecule upon His-4 protonation at the membrane/water interface. This is shown by analyzing the pH- and ionic strength dependence of binding of CTXs to phospholipid monolayers according to Gouy-Chapman theory. The protonation of the His-4 residue also results in a local conformational change in the loop I region since the chemical shifts of amide protons for the amino acid residues from Cys-3 to Thr-14 are all found to vary as a function of pH with an apparent pKa similar to that of His-4. Interestingly, the effect is relayed to other amino acid residues in the structural core of the protein such as those in C-terminal (Lys-60, Cys-61, and Asn-62) and triple-stranded antiparallel beta-sheet (Cys-22, Lys-24, Ala-25, Arg-38, and Ala-41) regions. An additional local conformational change in the molecule results around pH 5 as evidenced by circular dichroism spectroscopic studies, although this change does not affect the characteristic beta-sheet and three-finger loop structure of CTX molecule as revealed by two-dimensional NOESY 1H NMR study. The latter conformational change at acidic pH, however, completely inactivates CTX-induced aggregation/fusion activity of sphingomyelin vesicles. The results suggest that deciphering the functional sites of CTXs on the basis of structure and dynamics determined at low pH should be done with caution. Since 19 out of 44 CTX homologues with known amino acid sequence contain His-4, the effect of His-4 on the structure and function of CTX molecules is important and is discussed in terms of the diverse membrane targets of CTX subtypes. Also discussed is the pH-induced activation of snake venom proteins in the victim.

Animals↗

PubMed1994

Two distinct types of cardiotoxin as revealed by the structure and activity relationship of their interaction with zwitterionic phospholipid dispersions.

Cardiotoxins (CTXs) are a group of homologous proteins found in cobra snake venom and consist of 60-62 amino acid residues. Although CTXs are known to consist of three extended beta-sheet loops similar to neurotoxins, the target and interaction of CTXs with membranes unlike those of neurotoxins are not well understood. Herein, we report comparative studies of 10 CTXs purified from Taiwan cobra (Naja naja atra) and Mozambique spitting cobra (Naja mossambica mossambica) snake venoms with respect to their interactions with zwitterionic phospholipids. Based on the CTX-induced mixing of sphingomyelin vesicles and the binding of CTX to lysophosphatidylcholine micelles, two distinct types of CTX, i.e. P- and S-type CTX, are identified. P-type CTXs are characterized by the presence of Pro-31 within a putative phospholipid binding site near the tip of loop 2; whereas S-type CTXs are characterized by the presence of Ser-29 within the same but more hydrophilic region. Although binding of all CTXs to phospholipid membranes involves a phospholipid binding site at loop 1, P-type CTXs exhibit higher fusion and binding activity than S-type CTXs, presumably due to the additional phospholipid binding site at loop 2. The binding modes of P- and S-type CTX are thus different. Analysis of the primary structures of 46 CTXs from the genus Naja indicates that these two types of CTXs exist in all species examined. Reasonable structure/activity correlation can be detected for the effects of CTXs on muscle and red blood cells, although notable exceptions are also found. S-type CTXs are generally found to exhibit higher muscle cell depolarization activity, whereas P-type CTXs are found to possess a higher hemolytic activity. Thus the mechanism of action of CTXs seems to involve CTX-membrane interactions and depends on the type of the cell membrane and CTX molecules under study. The two lipid binding sites in P-type CTXs and one lipid binding site in S-type CTXs show large variation in their amino acid residues, but they do display some common distribution of residue type. Analogous to the signal sequences for protein import, these regions are characterized by the coexistence of an exposed hydrophobic surface flanked on either side by a cationic residue. A hypothesis is proposed to explain the general cytotoxic and specific cardiotoxic effect of CTXs based on the two CTX subtypes in snake venom.

Amino Acid Sequence↗

PubMed1994

Tumor recurrence in long-term survivors after treatment of carcinoma of the esophagus.

To evaluate the status of tumor recurrence and the possible factors relevant to tumor recurrence among patients who survived more than 5 years after subtotal esophagectomy for the treatment of squamous cell carcinoma of the esophagus, a total of 104 patients who received treatment between 1959 and 1986 were reviewed. In 18 of these 104 patients, local or distant tumor recurrence developed, for a tumor recurrence rate of 17.3%. Eleven (61.1%) of these 18 patients eventually died of carcinomatosis despite further radiotherapy or chemotherapy, or both, and 4 patients with the disease are still alive. Three patients continue to survive after aggressive therapy was instituted for control of the locally recurrent tumor. Sixty-nine of the 104 patients are alive without tumor recurrence after the initial esophagectomy, and the remaining 17 patients died of miscellaneous causes. Tumor recurrence appears to be the most important factor affecting the prognosis in long-term survivors with resectable esophageal carcinoma. Among the 11 patients who died of tumor recurrence, 10 died within 5 to 9 years of their esophagectomy. The incidence of various modes of tumor recurrence among these 18 patients was as follows: blood-borne metastasis, 61%; lymph node recurrence, 33%; and locoregional organ recurrence, 33%. Factors that may be pertinent to a higher tumor recurrence rate include male sex, moderate to poor tumor differentiation, the presence of lymph node metastasis, and late stage of disease (stage IIb or worse). However, we could not find any statistical significance among these possible factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Expression of multiple oncogenes in human esophageal carcinomas.

To study the oncogenesis of human esophageal carcinoma, the expression of a variety of oncogenes was studied in 10 esophageal carcinoma cell lines and 16 pairs of tumor and nontumor tissues removed from patients with esophageal carcinoma. Northern blot analyses using 11 different oncogene probes revealed that 5 oncogenes, i.e. c-myc, c-H-ras, c-sis, c-raf, and c-fos, were expressed. Among them, a variant c-sis mRNA transcript of 2.7 kilobase (kb) was expressed in 7 of 10 cell lines and in 9 of 16 tumor tissues. Furthermore, an overexpression and an amplification of c-myc gene was observed in some cell lines. These results suggest that multiple oncogene expression may be required for the induction, maintenance, and progression of esophageal carcinoma. The expression of a 2.7-kb transcript, of c-sis and overexpression of c-myc gene may play some role in the carcinogenesis of esophageal carcinoma.

Carcinoma, Squamous Cell↗

PubMed1994

Carcinosarcoma of the lung: an analysis of 6 operated cases.

BACKGROUND: Carcinosarcoma of the lung is a rare malignant pulmonary neoplasm, and constitutes 0.1% to 0.3% of all lung tumors. Typically, these tumor have both carcinomatous and sarcomatous components with a poor prognosis due to late diagnosis and early metastases. METHODS: From July 1980 to December 1993, six patients with pulmonary carcinosarcoma who underwent surgical treatment were studied. None of them had accurate tissue diagnosis before operation except one case with peripheral variant carcinosarcoma who was diagnosed by percutaneous transthoracic fine needle biopsy under sonographic guidance. All of our patients had a huge peripheral lung tumor 3.8 to 10 cm in diameter. Pneumonectomy was done in two patients, and lobectomy in three. The other patient had unresectable tumor. RESULTS: The histopathological components in carcinoma were epidermoid carcinoma in and adenocarcinoma in 3. Differentiation of sarcomatous lesions included spindle cell sarcoma in 3, fibrosarcoma in 2 and undifferentiated mesenchymal sarcoma in one patient. In the resectable group, 1 was at stage II and 4 were at stage IIIa. None of the patients survived more than 2 years due to distant metastasis and cachexia. The mean survival was 140 days. CONCLUSIONS: The carcinomatous portion tends to metastasize to regional lymph nodes whereas the sarcomatous part gives rise to systemic dissemination. Due to early systemic dissemination and poor prognosis, combination of extensive surgical intervention resection with aggressive postoperative chemotherapy and radiotherapy might be a reasonable consideration to improve survival in primary pulmonary carcinosarcoma.

Adult↗

PubMed1993

Solution structure of cardiotoxin V from Naja naja atra.

Cardiotoxins are small proteins that are found in the venoms of snakes from the Elapidae family. These toxins are known to bind to and disrupt the organization, integrity, and function of the cell membrane. Most of the well-studied cardiotoxins cause depolarization of membrane potentials and/or lysis of red cells. In contrast, CTX V from Naja naja atra displays poor hemolytic activity but is proficient at inducing aggregation and fusion of sphingomyelin vesicles [Chien et al. (1991) J. Biol. Chem. 266, 3252-3259]. To determine whether the unique activity of this CTX is attributable to its tertiary structure, the solution structure of CTX V was determined by NMR methods. On the basis of these studies, this cardiotoxin has the same general topology as other members of the family, and thus its unusual properties do not arise from any gross structural differences that are detectable by solution NMR methods. Molecular dynamics calculations indicate that residues 36-50 show concerted fluctuations. On the basis of sequence similarity, we postulate that residues 30-34 are important in determining the specificity of cardiotoxins for fusion versus lysis of vesicles.

Amino Acid Sequence↗

PubMed1993

Lymph node metastasis in patients with adenocarcinoma of gastric cardia.

BACKGROUND AND METHODS: Prospectively, a consecutive series of 42 patients undergoing extended radical total gastrectomies (R 3/4 lymph node dissection) for adenocarcinoma of the gastric cardia from January 1988 to June 1991 were studied. The aims of this study were to evaluate the status of lymph node metastasis and the relationship between the frequency of nodal involvement and the extent of the primary tumor invasion. The Japanese criteria was used for postoperative staging. RESULTS: The incidence of operative morbidity and mortality in the series were 40.5% and 9.5%, respectively. Twenty-two (52%) of the patients had lymph node metastasis. For those patients, the most common sites of nodal involvement were the lesser curvature (72.7%), pericardiac (68.2%), left gastric artery (45.5%), left greater curvature (31.8%), splenic artery (31.8%), and the hilum (22.7%), inferior paraesophageal (18.2%), and diaphragmatic (18.2%) regions. Only one skip lymph node metastasis was discovered. In addition, no lymph node metastasis was found in the following areas: hepatoduodenal ligaments, mesenteric root, right paraadrenal, and subcardial lymph nodes. CONCLUSIONS: The study's results demonstrate that there seemed to a correlation among the status of lymph node metastasis, tumor size, and the depth of tumor invasion. However, the depth of tumor invasion appears to be a more important factor than tumor size in influencing the status of lymph node metastasis. The local recurrence rate was 2.4%. Consequently, the authors recommend that for the tumor with mucosal invasion only, a relatively conservative lymphadenectomy may be sufficient, but for tumors that invade beyond the mucosal region, radical lymphadenectomy may be helpful in preventing local recurrence.

Adenocarcinoma↗

PubMed1992

Relationship of the queuine content of transfer ribonucleic acids to histopathological grading and survival in human lung cancer.

To elucidate the significance of tRNA hypomodified with queuine to the grade of malignancies in human solid tumors, the amount of tRNA having guanosine in place of queuosine was determined in human lung cancer and normal lung tissue, by exchanging the unmodified guanosine residue for [3H]guanine. The reaction is catalyzed by guanine:queuine tRNA transglycosylase. Total tRNA was extracted from 23 different lung cancer specimens and the precursor of isoacceptor tRNA that contains guanine instead of queuine in the first or wobble position of the anticodon [(Q-)tRNA] content was determined. In 12 cases the (Q-)-tRNA was determined in normal lung tissues as well. In each individual, the (Q-)tRNA content in lung cancer tissue was higher than that of the normal lung tissue. The (Q-)tRNA content was not correlated to the surgicopathological staging of the patients but was highly correlated to the histopathological classification of the tumors. The amounts of (Q-)-tRNA were 1.75 +/- 0.67 (SD), 2.36 +/- 0.89, 3.77 +/- 1.39, 5.18 +/- 2.32, and 7.65 +/- 1.34 pmol/A260 in normal, well, moderately, moderately to poorly, and poorly differentiated tumors. The difference from normal to moderately differentiated or less differentiated groups was significant (P less than 0.05). In 10 patients with (Q-)tRNA higher than 3.5 pmol/A260, their cancers relapsed and only 2 were alive after 4 years. In 11 patients with (Q-)tRNA less than 3.5 pmol/A260 in their lung cancer tissues, 7 patients were still alive without any evidence of disease, 3 were dead, and 1 had recurrence of disease. These results, taken together with other previous studies, suggest that a decreased queuosine content of tRNA may be a general feature of neoplasms and may be useful for grading malignancy and perhaps also for the prediction of survival in human lung cancer.

Carcinoma↗

PubMed1992

Malignant thymoma.

Sixty-one patients underwent operations for malignant thymomas between 1961 and 1989. Twenty-three patients had associated myasthenia gravis (MG), an incidence of 37.7%. Upon being admitted to the hospital, the patients' most common symptoms included chest pain, MG, cough, and dyspnea. Only 7 of 61 (11.5%) patients had no symptom. Tumor staging of 58 patients with invasive thymomas was performed according to Masaoka classification. The patients were classified as follows: Stage II disease, 5; Stage III, 41; Stage IVa, 8; and Stage IVb, 4. In addition, thymic carcinoma was present in three patients. The series had a resection rate of 55.7%. The incidence of operative complications was 16.3%. Only one patient died of myocardial infarction; the incidence of operative mortality was 1.6%. The patients with MG had a higher rate of resection (69.6%) and a higher incidence of complete thymectomy (14 of 23 patients; 60.9%). Mixed lymphoepithelial tumors and epithelial cell predominant tumors were the most frequent histologic patterns (45.9% and 34.4%, respectively). Fifty-two patients had postoperative radiation therapy, and 10 patients had chemotherapy. The overall cumulative survival rates in the series were 59% and 34% at 5 and 10 years, respectively. The results demonstrated that the factors affecting the prognosis may include resectability, postoperative irradiation or chemotherapy, MG, and tumor staging. The influence of histologic variation on survival rates could not be clearly defined in the series. Surgical resection, particularly complete thymectomy, followed by irradiation is the primary option of therapeutic management for malignant thymoma.

Adolescent↗

PubMed1992

Gastric substitution for resectable carcinoma of the esophagus: an analysis of 368 cases.

Between 1974 and 1984, 1,188 patients with esophageal malignancies were treated in the Division of Thoracic Surgery of Veterans General Hospital, Taipei. The rate of resectability was 42.6%. Since 1974, the stomach has been used as esophageal substitute, and through 1984, a total of 368 patients were collected. The routes of reconstruction included retrosternal (77.2%), posteromediastinal (7.1%), and intrathoracic (15.7%). The rates of postoperative complications and surgical mortality in these 368 patients were 26.3% and 6.5%, respectively. Leakage of anastomosis was the most frequent complication. The incidence of stricture of esophagogastrostomy was 25.5%. All strictures were relieved by esophageal dilations. An average of 3.9 esophageal dilations were performed per patient (range, 1 to 15). Radical lymph node dissection was not routinely performed in our series. The actuarial 2-year and 5-year survival rates were 26.4% and 7.6%, respectively. Among 76 patients undergoing cervical esophagogastrostomy and surviving for more than 1 year, late complications occurred as follows: acid/bile regurgitation, 46.1%; postprandial fullness of abdomen, 38.2%; dumping syndrome, 13.2%; distended stomach with dyspnea, 11.8%; aspiration pneumonia, 6.6%; and gastric ulcer, 6.6%. Moreover, compared with patients without pyloroplasty, those with pyloroplasty were found to have a higher incidence of bile regurgitation (55.5% versus 8.6%), dumping syndrome (33.3% versus 6.9%), aspiration pneumonia (16.7% versus 3.4%), and gastric ulcer (22.2% versus 1.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Surgical treatment of diaphragmatic eventration in adults.

Surgical intervention of diaphragmatic eventration is urgent and life-saving in infants but is rarely in adults. In the past 22 years, Seven adults with diaphragmatic eventration were encountered at the Division of thoracic surgery, Dept. of surgery, VGH, Taipei. The age on diagnosis ranged from 32 to 65 years with mean of 44 years old. Male and left diaphragm were more frequently affected (6 men, 1 woman; 6 left, 1 right). All of them received operation of plication. In spite of good immediate postoperative return of the diaphragms to normal position with clinical improvement found in all patients, 5 dyspneic patients were found to have gradual diaphragmatic rise or relapse of respiratory symptoms after repair. Diaphragmatic eventration could cause compression of lung by abdominal organs and reinforcement of diaphragm through plication might increase the diaphragm strength and diminish the clinical symptoms. Yet according to our series, we recommend surgical intervention is only for existence of distress stemmed from it and unresponsive to medical therapy.

Adult↗

PubMed1991

Fusion of sphingomyelin vesicles induced by proteins from Taiwan cobra (Naja naja atra) venom. Interactions of zwitterionic phospholipids with cardiotoxin analogues.

Egg sphingomyelin vesicles were used to assay aggregation/fusion activities of proteins from Taiwan (Naja naja atra) venom to avoid the problem of phospholipase A2 contamination during protein purification. It led to the identification of a new cardiotoxin (CTX) analogue protein (CTX V) with major aggregation/fusion, but few hemolysis, activities. On the contrary, cardiotoxin (CTX III) induced significant hemolysis of human red blood cells but exhibited few aggregation/fusion activities. To study the structure/activity relationship of these CTX-induced processes, the amino acid sequence of CTX V was determined and its aggregation/fusion activity was compared with that of CTX III by transmission electron microscopy, quasielastic laser light scattering, differential scanning calorimetry, and fluorescence spectroscopy. The results show that the CTX-induced fusion process at temperatures slightly above that of the gel to liquid-crystalline phase transition of sphingomyelin vesicles can ultimately convert small sonicated vesicles into large fused vesicles with sizes of 1-2 microns. The abilities of CTX V to induce the leakage of sphingomyelin vesicles content and to cause the fusion of vesicles are approximately 10-fold higher than those of CTX III. Based on the CTX structures determined in the present and other studies, it is suggested that the amino acid residue X within the well conserved sequence of -Cys-Pro-X-Gly-Lys-Gln-Leu-Cys- plays a role in the interaction of CTX with lipid molecules. The lipid phase transition could further enhance the protein-lipid interaction in the process leading to the fusion of vesicles.

Amino Acid Sequence↗

PubMed1990

Formosanin-C, an immunomodulator with antitumor activity.

Paris formosana Hayata (Liliaceae) grown in the mountain areas of Taiwan, has been used as a folk remedy for snake bite, and as an anti-inflammatory or anti-neoplastic agent. The effects of formosanin-C, a diosgenin saponin isolated from Paris formosana, on immune responses and transplantable murine tumor were studied. In culture systems, formosanin-C (0.03-0.16 microM) displayed significant enhancement of the blastogenic response of human peripheral blood cells to phytohemagglutinin. Formosanin-C also significantly increased the 3H-thymidine incorporation of ConA-stimulated lymphocytes at concentrations of 0.1 and 0.01 microM. The responsiveness of the granulocyte/macrophage colony-forming cells (GM-CFC) to mouse fibroblast cells L929 conditioned medium was altered in the presence of 0.01 and 0.001 microM of formosanin-C. In addition, formosanin-C given intraperitoneally activated natural killer cell activity at doses of 1-2.5 mg/kg. An intraperitoneal injection of 2.5 mg/kg of formosanin-C markedly induced interferon production, the peak blood level of which was observed 24 h after formosanin-C injection. Growth of subcutaneously transplanted MH134 mouse hepatoma was retarded by intraperitoneal treatment with 1-2.5 mg/kg of formosanin-C. The activity of 5-fluorouracil against MH-134 mouse hepatoma was potentiated by intraperitoneal treatment with formosanin-C. These results suggest that formosanin-C might display antitumor activity in association with modification of the immune system.

Adjuvants, Immunologic↗

PubMed1989

Reconstruction of the esophagus with the left colon.

This report reviews our experience with 96 patients with benign or malignant stricture of the esophagus who underwent interposition of the left colon with or without esophageal resection from July 1982 to June 1987. There were 67 male and 29 female patients ranging in age from 8 to 80 years. Thirty-seven patients had fibrotic stricture secondary to corrosive injury of the esophagus, 42 had cancer of the esophagus, and 17 had cancer of the gastric cardia. The incidence of postoperative complications and surgical mortality, respectively, was 16.2% and 2.7% for patients with corrosive stricture of the esophagus, 35.7% and 11.9% for patients with cancer of the esophagus, and 35.2% and 5.8% for patients with cancer of the gastric cardia. Reconstruction resulted in good function in 75.6% of the patients with corrosive stricture of the esophagus, 66.6% of the patients with cancer of the esophagus, and 70.5% of patients with cancer of the gastric cardia. The morbidity and mortality were higher in the group with malignant esophageal strictures because of advanced age, poor general condition of the patient, and extent of the surgical procedure needed. Cervical anastomotic leakage was the most frequently encountered complication (13.5%), and all the poor-function results were caused by this complication. In our experience, reconstruction of the esophagus with left colon is a satisfactory method that can be accomplished with acceptable morbidity and mortality. The left colon is a durable and functional substitute.

Adolescent↗

PubMed1989

Combined modality treatment for non-small cell lung cancer. Lung Cancer Study Group.

A total of 265 patients with non-small cell lung cancer at stages 1 and 2 by preoperative clinical staging were divided into 4 stages after exploratory thoracotomy. Patients at each stage were further divided into subgroups to receive different adjuvant therapies. The cumulative 5-year survival rate showed to be 44.4% for stage 1, 35.5% for stage 2, 7.4% for stage 3 and 0% for stage 4. Histologically, the rate was 28.8% for squamous cell carcinoma, 23.4% for adenocarcinoma, and 29.8% for large cell carcinoma and carcinoma poorly differentiated. For patients at stage 1, it made no significant difference whether they underwent surgical resection only or combined with postoperative intrapleural BCG injection. For patients at stage 2, there was no significant difference between surgical resection only and resection combined with postoperative radiotherapy. For patients at stage 3, who underwent surgical resection combined with chemotherapy and/or radiotherapy, it seemed that combined chemotherapy and radiotherapy presented better results than radiotherapy or chemotherapy alone.

Carcinoma, Non-Small-Cell Lung↗

PubMed1989

Primary mediastinal seminoma.

Primary mediastinal seminoma is a rare neoplastic disease. Only 133 cases have been reported in the literature. Five patients with primary mediastinal seminoma had been treated at VGH from 1974 to 1986. All of them received exploratory thoracotomy but only two of them were resectable. Postoperative radiation therapy was given regardless of resection. One had additional chemotherapy due to nodal involvement. All five patients showed complete resolution and were alive and free of disease for an average follow-up period of 42.6 months (range, 5-82 months). So we conclude that mediastinal seminoma is a rare neoplastic disease and can be treated primarily by surgery. Irradiation can also induce complete remission and long term survival in those with unresectable tumors.

Adult↗

PubMed1988

The effect of lipopolysaccharide on the production of GM-EA, GM-CSA, and PGE2 by human monocyte-derived lipid-containing macrophages.

Monocyte-derived lipid-containing macrophage (MDLM) was the major source of granulomonopoietic enhancing activity (GM-EA) but these well-differentiated cells were unable to synthesize constitutively the granulocyte-macrophage colony-stimulating activity (GM-CSA) that was contributed mostly by the younger monocytoid cells. The presence of various concentrations (0.5-10 micrograms/ml) of lipopolysaccharide (LPS) potentiated the production of GM-EA by MDLM. Enhancement of GM-EA production peaked at about 0.5 micrograms/ml of LPS, but at higher doses (10-40 micrograms/ml) LPS became suppressive. In parallel, LPS-induced production of prostaglandin E2 (PGE2) was observable only at higher doses (10-40 micrograms/ml), suggesting a correlation between PGE2 production and LPS-mediated suppression of GM-EA synthesis. At optimal concentration (0.5 micrograms/ml), LPS could effectively override the inhibitory effect of interferon-gamma on the production of GM-EA. In addition, GM-CSA production by MDLM can be partly restored by stimulation with high doses of LPS (10-40 micrograms/ml). These results suggest that MDLMs have functional potentials similar to the younger macrophages and may play an important role in the regulation of myelopoiesis through the release of GM-EA and related regulators.

Colony-Stimulating Factors↗