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Biomedical subjects

S Tsai

Publications and source records attributed to S Tsai.

At least 73 records · Page 4Linked to original sources
PubMed1993

Chromosome studies in HTLV-I, -II, and HIV-1, -2 cell lines infected in vivo and in vitro.

HTLV-I, II and HIV-1, 2 are T-cell tropic viruses, all belonging to the retrovirus family. These viruses are transmitted horizontally by intimate contact or through blood products. The study of chromosomal changes in these T cells may enhance our understanding of the nature and mechanism of these viral infections. However, because of the cytopathic effect of these viruses on T cells, the direct observation of abnormalities in these cells is sometimes difficult. We performed chromosomal analysis on six HTLV-I cell lines from patients with HTLV-I-positive leukemia/lymphoma, one HTLV-I variant cell line, and two HTLV-II-positive cell lines. The results of these studies were compared with the findings in an earlier (published) study of direct preparations and short-term cultures of cells from 11 HTLV-I-positive NIH patients. Our study also included cytogenetic analysis of seven established cell lines and six normal peripheral bloods infected in vitro with the HTLV-IIIB strain of HIV-1 (five cell lines and six bloods) or HIV-2 (two lines); all were studied both before and after viral infection. The results showed that all six HTLV-I cell lines and the variant cell line had multiple chromosomal changes: three lines had deletions of chromosome 6, with breakpoints between q21 and q25. Nine of the 11 NIH patients with HTLV-I had clonal abnormalities, and six of these nine had chromosome 6 deletions with breakpoints ranging from band q11 to band q23. The high incidence of 6q involvement may be of considerable significance in this clinical subgroup of HTLV-I patients. The two HTLV-II cell lines were established from patients suffering from HTLV-II infection. Both of these cell lines had translocations of chromosome 21 at p11, and both had extra copies of chromosome 20; no known oncogenes or receptors are located on these two chromosomes. Chromosome 17 was the chromosome most frequently involved (three lines) in the five HIV-1-infected cell lines, followed by chromosomes 3 and 21; it is of interest that NGL (also known as C-ERBB2 or NEU oncogene), CD7 (a lymphocyte antigen), HTLV-1 receptor, NGFR (nerve growth factor receptor), and MIC6 are all cell surface antigens coded by genes on chromosome 17q. No specific chromosome abnormalities were found in the normal blood samples infected with HIV-1, and no unique chromosome changes were noted in the two cell lines infected with HIV-2; however, the infected H9 line had a chromosome 17 abnormality, a translocation involving band 17p11.

Cell Line↗
PubMed1992

A mutated retinoic acid receptor-alpha exhibiting dominant-negative activity alters the lineage development of a multipotent hematopoietic cell line.

The retinoic acid receptor (RAR alpha) is expressed in virtually all hematopoietic lineages, but the role of this transcription factor in regulating the growth and differentiation of hematopoietic progenitors is unknown. We have constructed a mutant RAR alpha that both exhibits dominant-negative activity against the normal RAR alpha in transient expression assays in mouse fibroblasts and inhibits retinoic acid-induced neutrophilic differentiation of the HL-60 human promyelocytic leukemia cell line. When this dominant-negative RAR alpha construct is introduced into the multipotent interleukin-3-dependent FDCP mix A4 murine hematopoietic cell line, there is a rapid switch from spontaneous neutrophil/monocyte differentiation to basophil/mast cell development. Thus, in this multipotent hemopoietic cell line the normal RAR alpha transcription factor and/or related molecules appear to promote the differentiation of neutrophils and monocytes but suppress the development of basophils/mast cells.

3T3 Cells↗
PubMed1991

Enhancement of HIV-1 cytocidal effects in CD4+ lymphocytes by the AIDS-associated mycoplasma.

Coinfection with Mycoplasma fermentans (incognitus strain) enhances the ability of human immunodeficiency virus type-1 (HIV-1) to induce cytopathic effects on human T lymphocytes in vitro. Syncytium formation of HIV-infected T cells was essentially eliminated in the presence of M. fermentans (incognitus strain), despite prominent cell death. However, replication and production of HIV-1 particles continued during the coinfection. Furthermore, the supernatant from cultures coinfected with HIV-1 and the mycoplasma contained a factor that inhibited the standard reverse transcriptase enzyme assay. The modification of the biological properties of HIV-1 by coinfection with mycoplasma may be involved in the pathogenesis of acquired immunodeficiency syndrome (AIDS).

Acquired Immunodeficiency Syndrome↗
PubMed1990

COUP-TF gene: a structure unique for the steroid/thyroid receptor superfamily.

Two different genomic genes for the COUP-transcription factor, COUP-TF I and COUP-TF II, have been isolated from a human cosmid genomic library using a [32P]-labeled cDNA probe. Data obtained from Southern blot analysis of these cosmid clones indicated that two closely related genes exist in the human genome and have a similar genomic organization. The genes are similar in the hormone and DNA binding domains but diverge from one another in the N-terminal region. Using DNA sequencing and polymerase chain reaction (PCR) techniques we have determined that the structure of COUP-TF I consists only of three exons and two introns. Surprisingly, both zinc fingers (i.e., F1 and F2) are located in the first exon. Therefore, COUP-TF I is unique among the members of the steroid/thyroid hormone receptor superfamily which have been described to date.

Amino Acid Sequence↗
PubMed1990

Levels of rifampin and ciprofloxacin in nasal secretions: correlation with MIC90 and eradication of nasopharyngeal carriage of bacteria.

To predict the efficacy of antibiotics in eliminating nasopharyngeal carriage of organisms such as Neisseria meningitidis, Haemophilus influenzae, and methicillin-resistant Staphylococcus aureus (MRSA), a novel approach for measuring drug concentrations in nasal secretions was developed. Five healthy individuals received four doses of rifampin and then, at a later date, ciprofloxacin. At 2, 5, and 8 h after the last dose, serum, saliva, and cold-stimulated nasal secretion samples were collected, and drug levels were analyzed by high-performance liquid chromatography. Nasopharyngeal levels of rifampin reached but did not substantially exceed 90% of the minimal inhibitory concentration (MIC90) for H. influenzae, exceeded the MIC90 for N. meningitidis, and were well above that for MRSA. Ciprofloxacin levels in nasal secretions far exceeded the MIC90 for meningococci and Haemophilus organisms but were below that for MRSA. These findings are consistent with the clinical studies showing that rifampin eliminates, in most instances, the nasal carriage of N. meningitidis and to a lesser extent H. influenzae. A single dose of ciprofloxacin has been shown to eradicate meningococci, yet a long course of treatment with this drug is not adequate for MRSA. On the basis of these results, clinical trials with ciprofloxacin to eliminate nasopharyngeal carriage of H. influenzae appear to be warranted.

Carrier State↗
PubMed1988

Interleukin-1 regulation of hematopoietic growth factor production by human stromal fibroblasts.

The human stromal fibroblastoid cell strain designated ST-1 represents a normal population of cells capable of supporting hematopoiesis in vitro. These cells constitutively elaborate hematopoietic growth factor activity into the medium and the level of production of this activity dramatically increases following stimulation of the cells with IL-1. This enhanced production is due at least in part to increased expression of the genes for GM-CSF, G-CSF, and IL-6, but not IL-3. The IL-1 treatment had little effect on the expression of M-CSF, a factor made constitutively by the cells. These results are consistent with the model that hematopoiesis is regulated at least in part by constant short-range interactions of humoral factors produced by stromal cells both with other types of stromal cells and with the hematopoietic progenitors.

Animals↗
PubMed1988

Somatostatin analogue (SMS 201-995) in patients with gastrinomas.

We have examined the effects of the somatostatin analogue (SMS 201-995) in 10 patients with gastrinoma syndrome. Four had hepatic metastases, one had a tumor in a peripancreatic lymph node, two had resectable intrahepatic and intraduodenal gastrinomas, and in three the primary tumor was not found. Acutely, SMS 201-995 decreased acid secretion and restored the BAO/MAO ratio to normal in eight of eight patients. Basal and secretin-stimulated gastrin responses were suppressed but not normalized in eight of eight patients. Suppression of endogenous gastrin restored responsiveness to exogenous gastrin. Treatment for up to 12 months with SMS 201-995 controlled symptoms in six of eight patients, suppressed serum gastrin in three of five, and suppressed acid secretion in three of three patients. Treatment with SMS 201-995 in three patients for 5 months decreased tumor secretion of gastrin and diminished basal acid secretion, an effect that persisted in two of three patients 48 hours after withdrawal of SMS. In patients with metastatic disease who had high levels of gastrin, SMS treatment for 5 to 12 months did not inhibit tumor growth or decrease gastrin levels. SMS treatment arrested progression of tumor growth only in patients who had a reduction in gastrin and gastric acid secretion. We conclude that SMS may be useful in the management of gastrinoma patients by decreasing hypersecretion of gastrin and gastric acid and, over a longer term, may even change tumor capacity to release gastrin and gastric acid secretion. SMS may thus be useful as a palliative agent and as an adjunct to conventional treatment of the gastrinoma syndrome. SMS does not appear to shrink tumor mass in patients with very high basal gastrin levels.

Adult↗
PubMed1987

Cytogenetics in hereditary malignant melanoma and dysplastic nevus syndrome: is dysplastic nevus syndrome a chromosome instability disorder?

Analysis of peripheral blood lymphocyte Giemsa-banded karyotypes was performed on 163 family members from 13 melanoma-prone families. Patients were classified regarding the presence of cutaneous melanoma and dysplastic nevi (a well characterized melanoma precursor), and each karyotype was scored for the number of cells containing the following: major structural, minor structural, and numerical abnormalities. No clonal cytogenetic abnormalities were observed. Cutaneous malignant melanoma and dysplastic nevi syndrome patients each had increased abnormalities of all types combined, compared with pooled controls (i.e., normal family members, and spouses; respectively, chi 2 = 6.02, p = 0.01; chi 2 = 5.29, p = 0.02). There was a statistically significant p-value for major structural abnormalities for melanoma patients and numerical abnormalities for the dysplastic nevi patients. Minor structural abnormalities did not differ in any of the groups. In addition, studies of ultraviolet induced sister chromatid exchange, in vitro tetraploidy, and extended prophase banding were performed on a limited number of patients. No significant differences between cases and controls were observed in these tests. Our data suggest that a chromosome instability abnormality may contribute to the pathogenesis of hereditary melanoma.

Adult↗
PubMed1987

Interleukin 1 induces cultured human endothelial cell production of granulocyte-macrophage colony-stimulating factor.

Monokine-stimulated endothelial cells are known to produce both burst- and colony-stimulating activities, but neither the nature of the monokine nor the hematopoietic growth factor(s) produced is known. We show by mRNA analysis that an immortalized line of human endothelial cells constitutively produce granulocyte-macrophage colony-stimulating factor. Furthermore, interleukin 1 and tumor necrosis factor induce early passage human umbilical endothelial cells to produce the same growth factor.

Bone Marrow Cells↗
PubMed1987

Differential binding of erythroid and myeloid progenitors to fibroblasts and fibronectin.

Using a novel coverslip-transfer culture technique, we recently demonstrated that primitive erythroid burst-forming units (BFU-E) can migrate, proliferate, and differentiate in intimate association with stromal fibroblastoid cells in the presence of serum proteins and erythropoietin. No other exogenous hemopoietic growth factors are required. Most of the colonies that develop in this system are very large erythroid bursts, and very few granulocyte-macrophage (GM) colonies are observed. In this report, we present data indicating that the predominance of erythroid burst colonies in this culture system is due to preferential binding of primitive erythroid progenitors to the stromal fibroblastoid cells and not to differential stimulation of these erythroid progenitors by these cells. We next show that the binding of BFU-E to stromal cells is blocked by anti-fibronectin antibodies. Finally, we demonstrate the preferential binding of BFU-E to fibronectin by using glass coverslips or Petri dishes coated with purified human plasma fibronectin. The binding is blocked by a monoclonal antibody specific for the cell-binding domain of fibronectin. We conclude that: primitive erythroid progenitors bind strongly whereas G and/or M progenitors (CFU-G/M) bind only weakly to fibronectin; primitive erythroid progenitors bind to the cell-binding domain on the fibronectin molecule; and erythroid progenitors and precursors remain bound to fibronectin throughout differentiation.

Bone Marrow Cells↗
PubMed1986

Cytogenetic characterization of selected small round cell tumors of childhood.

Small, round, blue-cell tumors (SRCT), including rhabdomyosarcoma, Ewing's sarcoma of bone and soft tissue, mesenchymal chondrosarcoma, small cell osteosarcoma, hemangiopericytoma, neuroblastoma, peripheral neurectodermal tumor (peripheral neuroepithelioma of bone and soft tissue), and the malignant small cell tumor of the thoracopulmonary region described by Askin (Askin's tumor), are often difficult to distinguish by light microscopy. We have evaluated the cytogenetics of these tumors by studying 24 tumor explants in short-term culture and 22 tumor cell lines. In Ewing's sarcoma (a tumor of unknown histogenesis), and in peripheral neuroepithelioma and Askin's tumor (tumors with evidence of neural origin), we have observed an indistinguishable t(11;22) translocation.

Adolescent↗
PubMed1986

Isolation of a human stromal cell strain secreting hemopoietic growth factors.

A diploid fibroblastoid cell strain, termed "ST-1," has been established from a long-term liquid culture of human fetal liver cells. ST-1 cells are nonphagocytic, nonspecific esterase negative and do not possess factor VIII-related antigen but stain with antibodies specific for fibronectin and type I collagen. The ST-1 cells produce nondialyzable hemopoietic growth factors capable of stimulating the development of erythroid bursts, mixed granulocyte-macrophage colonies, pure granulocyte colonies, and pure macrophage colonies. These factors are active on both human fetal liver and human adult bone marrow progenitors. When liquid cultures of human fetal liver hemopoietic progenitors are established with a preformed monolayer of ST-1 cells, the yields of nonadherent cells, erythroid progenitors, and myeloid progenitors are greatly increased. These studies demonstrate that the fibroblastoid ST-1 cells support hemopoiesis in vitro and may be a critical element in the stromal microenviroment in vivo.

Cell Division↗
PubMed1986

[Studies on urolithiasis. The histochemistry of the kidney tissues and stones from patients with urolithiasis].

In this study, 17 kidney tissue specimens and 29 renal stones were obtained from patients with urolithiasis. Control kidney specimens were dissected from 7 individuals not suffering from urolithiasis. The tissue specimens were fixed with 1% cetylpiridinium chloride (CPC) in 10% formalin (for 24 hours at room temperature). Then the kidney tissue specimens were embedded in paraffin and stained with hematoxylin-eosin for general observation as well as histochemically for demonstration of complex carbohydrates. Also, stone specimens were embedded in epon and thin sections made by the mineral polishing specimen preparation, and stained along with the kidney tissues. For identifying individual acidic and neutral carbohydrates, the enzyme digestion was performed for some tissue sections prior to histochemical staining. The stone-forming kidney tissues, normal kidney tissues and urinary stones (calcium oxalate, mixed, struvite) contained some glycosaminoglycans and neutral glycoproteins, but uric acid stones and cystine stones did not. The results of digestion with enzymes indicated that calcium oxalate stone-forming kidney tissue contains heparitin (heparan) sulfate; mixed stone-forming tissue contains sialic acid, hyaluronic acid, chondroitin sulfate A, B, C and heparitin (heparan) sulfate; struvite stone-forming tissue contains sialic acid, hyaluronic acid, chondroitin sulfate A, C and heparitin (heparan) sulfate; and cystine stone-forming tissue contains sialic acid, chondroitin sulfate A, C and heparitin (heparan) sulfate. The stone organic matrix is classified into the amorphous and stratiform types. The amorphous type matrix contains chondroitin sulfate A, B, C and heparitin (heparan) sulfate, and the stratiform type matrix also contains sialic acid and hyaluronic acid. The stone-forming kidney tissues, normal kidney tissues and stones (calcium oxalate, mixed, struvite) contain an appreciable amount of alpha-D-glucose, alpha-D-mannose and beta-D-galactose, but the uric acid stones and cystine stones do not contain sugar residues. Since the specific glycosaminoglycan composition differed for kidneys of different mineral content and stones of different morphological type, we believe that some glycosaminoglycans in kidneys and amorphous type matrix might play the role of a nucleating agent, and that a stratiform type matrix encourages stone enlargement.

Adult↗
PubMed1986

Stromal cell-associated erythropoiesis.

A novel cover slip-transfer culture system was designed to study the functional roles of stromal cells in hemopoiesis, particularly erythropoiesis. Human bone marrow stromal cell colonies were allowed to develop on small glass cover slips in liquid medium. The cover slips, along with the stromal cell colonies and progenitors attached to them were then transferred to a new tissue culture dish and overlaid with methylcellulose culture medium. No exogenous colony-stimulating factors except erythropoietin were supplied. Large erythroid bursts, comprising multiple subcolonies, developed on the stromal cells. In order to determine if stromal fibroblasts together with erythropoietin and serum proteins could support erythroid development, human bone marrow cells depleted of monocytes, macrophages, and T lymphocytes were allowed to adhere to monolayers of a homogeneous fibroblastoid human stromal cell strain ST-1 grown on cover slips. The cover slips were then washed to remove nonadherent cells, transferred to a new culture dish, and overlaid with methylcellulose culture medium containing fetal calf serum and erythropoietin. In this modified system as well, primitive erythroid progenitors migrated extensively on and within the stroma to form huge colonies of hemoglobinized erythroblasts that proceeded to enucleate. Our results indicate that (1) ST-1 cells together with serum proteins and erythropoietin can support the development of large erythroid bursts; (2) erythroid progenitors and precursors adhere to and migrate on and within the extracellular matrix elaborated by ST-1 cells; (3) erythroid progenitors are more adherent to the ST-1 cells or the extracellular matrix than are the more mature cells and possibly the myeloid progenitors.

Blood Proteins↗