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Biomedical subjects

J B Kim

Publications and source records attributed to J B Kim.

At least 73 records · Page 4Linked to original sources
PubMed1998

Effect of stem cell factor, interleukin-6, nitric oxide and transforming growth factor-beta on the osteoclast differentiation induced by 1 alpha,25-(OH)2D3 in primary murine bone marrow cultures.

Osteotropic hormones and cytokines are involved in the differentiation of osteoclast progenitors from haematopoietic stem cells to multinucleated osteoclasts which mediate bone resorption. Stem cell factor, interleukin-6, nitric oxide, and transforming growth factor-beta are implicated in the regulation of bone resorption by osteoclast. We test whether stem cell factor, interleukin-6, nitric oxide, and transforming growth factor-beta affect the generation of osteoclast-like multi-nucleated cells induced by 1 alpha,25-(OH)2D3. 1 alpha,25-(OH)2D3 increase the generation of osteoclast-like cells retaining osteoclast characteristics including multinuclearity and positive staining for tartrate-resistant acid phosphatase. Combined treatment of stem cell factor with interleukin-6 synergistically potentiates the ability of 1 alpha,25-(OH)2D3 to generate tartrate-resistant acid phosphatase-positive multinucleated cells. However, either stem cell factor or interleukin-6 alone does not induce the generation of tartrate-resistant acid phosphatase-positive multinucleated cells. Transforming growth factor-beta produces a biphasic effect on osteoclast generation induced by 1 alpha,25-(OH)2D3. Transforming growth factor-beta stimulates osteoclast generation at low concentration (0.1 ng/ml) whereas it suppresses the formation of osteoclast-like cell at higher concentration (1 ng/ml). Sodium nitroprusside, a donor of nitric oxide, almost completely inhibits the generation of 1 alpha,25-(OH)2D3-induced osteoclast at high concentration (100 microM), but it significantly enhances the osteoclast generation at low concentrations (3 microM). These results suggest that stem cell factor, interleukin-6, transforming growth factor-beta, and nitric oxide interact with 1 alpha,25-(OH)2D3 to modulate the differentiation of hematopoietic precursors toward committed osteoclast precursors.

24,25-Dihydroxyvitamin D 3↗
PubMed1998

Detection of human granulocytic ehrlichiosis agent and Borrelia burgdorferi in ticks by polymerase chain reaction.

Adult ixodid ticks were collected from Westchester County, New York, and Ipswich, Massachusetts, to determine the presence of infection with a human granulocytic ehrlichiosis (HGE) agent by using the polymerase chain reaction (PCR). The presence of Borrelia burgdorferi in ticks collected from New York was also determined by PCR. Of the 229 ticks from New York and 47 ticks from Massachusetts, 9% (22/229) and 25% (12/47) of ticks contained HGE agent, respectively. Fifty-four percent (123/229) of the ticks collected from New York were B. burgdorferi positive; 4% (9/229) of these ticks contained both HGE agent and B. burgdorferi. This finding indicates that animals with Lyme borreliosis may be also exposed to the etiologic agent of HGE. More extensive laboratory diagnosis may be necessary when multiple tick-borne diseases are suspected in animals.

Animals↗
PubMed1998

A case of Behçet's syndrome with supeior vena cava syndrome.

Behçet's syndrome is a multi-systemic and chronic disorder that affects many organs. It has been suggested that the diagnosis was based on the presence of the 'major' and 'minor' clinical criteria. When thromobophlebitis, arthritis, central nervous system or gastrointestinal lesions are also present. Behçet's syndrome will be thought to be present in the appropriate geographic area. We report a case of superior vena cava syndrome caused by Behçet's disease in a 40-year-old man with recurrent oral aphthous ulcers and skin rashes on the anterior chest wall. There were multiple thrombosis of the superior vena cava, innominate and subclavian veins. This patient also had a solitary cecal ulcer with an ileocecal fistula and downhill varix. The chest CT, veno-cavography, pulmonary angiography and colon study were taken and follow-up was performed.

Adult↗
PubMed1998

Enhanced expression of immunoglobulin kappa light chains with unusually long CDR3 regions in patients with rheumatoid arthritis.

OBJECTIVE: Our previous sequence analysis of immunoglobulin kappa light chains revealed that some patients with rheumatoid arthritis (RA) expressed repertoires enriched for transcripts containing unusually long CDR3 lengths of 11 amino acid codons. This was due, in part, to N region addition at the Vkappa-Jkappa joins. In this study, we analyzed a larger number of individuals to determine how often enrichment of kappa light chain repertoires for 11 amino acid CDR3 occurs in synovial lymphocytes and peripheral blood lymphocytes (PBL) of individuals with RA. METHODS: To measure length variability of kappa chain CDR3 regions, we performed a 2 stage polymerase chain reaction amplification and polyacrylamide gel electrophoresis. We sampled PBL and synovial lymphocytes of 9 patients with longstanding RA, and used PBL of 9 age and sex matched healthy individuals as controls. RESULTS: In PBL of healthy individuals, there was low level but consistent expression of kappa chains containing CDR3 with 11 amino acids. In patients, there was enhanced expression of kappa chains containing CDR3 with 11 amino acids compared to healthy individuals. This enhanced expression of kappa chains containing CDR3 of 11 amino acids was more pronounced in synovial lymphocytes compared to PBL of the same patients. CONCLUSION: These findings suggest that there is antigenic selection of B cells bearing antibodies with unusually long kappa light chain CDR3 in RA.

Adult↗
PubMed1997

Multiple sequence elements are involved in the transcriptional regulation of the human squalene synthase gene.

The expression of human squalene synthase (HSS) gene is transcriptionally regulated in HepG-2 cells, up to 10-fold, by variations in cellular cholesterol homeostasis. An earlier deletion analysis of the 5'-flanking region of the HSS gene demonstrated that most of the HSS promoter activity is detected within a 69-base pair sequence located between nucleotides -131 and -200. ADD1/SREBP-1c, a rat homologue of sterol regulatory element-binding protein (SREBP)-1c binds to sterol regulatory element (SRE)-1-like sequence (HSS-SRE-1) present in this region (Guan, G., Jiang, G., Koch, R. L. and Shechter, I. (1995) J. Biol. Chem. 270, 21958-21965). In our present study, we demonstrate that mutation of this HSS-SRE-1 element significantly reduced, but did not abolish, the response of HSS promoter to change in sterol concentration. Mutation scanning indicates that two additional DNA promoter sequences are involved in sterol-mediated regulation. The first sequence contains an inverted SRE-3 element (Inv-SRE-3) and the second contains an inverted Y-box (Inv-Y-box) sequence. A single mutation in any of these sequences reduced, but did not completely remove, the response to sterols. Combination mutation studies showed that the HSS promoter activity was abolished only when all three elements were mutated simultaneously. Co-expression of SRE-1- or SRE-2-binding proteins (SREBP-1 or SREBP-2) with HSS promoter-luciferase reporter resulted in a dramatic increase of HSS promoter activity. Gel mobility shift studies indicate differential binding of the SREBPs to regulatory sequences in the HSS promoter. These results indicate that the transcription of the HSS gene is regulated by multiple regulatory elements in the promoter.

Animals↗
PubMed1997

Identification of glycerol-3-phosphate acyltransferase as an adipocyte determination and differentiation factor 1- and sterol regulatory element-binding protein-responsive gene.

We demonstrate that the mRNA levels of glycerol-3-phosphate acyltransferase (GPAT), a mitochondrial enzyme catalyzing the initial step in glycerolipid synthesis, are induced during the differentiation of 3T3-L1 preadipocytes to adipocytes and following ectopic expression of rat adipocyte determination and differentiation factor 1 (ADD1), a protein with high homology to the human sterol regulatory element-binding protein-1 (SREBP-1). The increase in GPAT mRNA levels that occurs during differentiation is partially prevented by ectopic expression of a dominant negative form of ADD1. Nucleotide sequences corresponding to the proximal promoter of the murine mitochondrial GPAT gene (Jerkins, A. A., Liu, W. R., Lee, S., and Sul, H. S. (1995) J. Biol. Chem. 270, 1416-1421) bound SREBP-1a and NF-Y in electromobility shift assays. In addition, GPAT promoter-luciferase reporter genes were stimulated by co-expression of SREBP-1a. This increase was attenuated when either a dominant negative form of NF-Y was co-transfected into the cells or when the GPAT promoter contained mutations in the putative binding sites for SREBP-1a or NF-Y. These studies demonstrate that the regulated expression of the mitochondrial GPAT gene requires both NF-Y and ADD1/SREBPs. Thus, SREBPs/ADD1 regulate not only genes involved in cholesterol homeostasis and fatty acid synthesis but also a key enzyme in glycerolipid synthesis.

Adipocytes↗
PubMed1997

Distributional characteristics of the mRNA for retinoid Z receptor beta (RZR beta), a putative nuclear melatonin receptor, in the rat brain and spinal cord.

We investigated the distribution of retinoid Z receptor beta (RZR beta), a putative nuclear melatonin receptor, mRNA in the rat brain and spinal cord using in situ hybridization. The RZR beta riboprobe uniquely hybridized with the neurons in several sensory pathways including the dorsal horn of the spinal cord, whereas the regions involved in the motor control were generally unlabeled. RZR beta mRNA was also highly expressed in the dorsomedial portion of the suprachiasmatic nucleus, pars tuberalis and some limbic areas. This result suggests that RZR beta plays a specific role as a transcription factor in the sensory, neuroendocrine and limbic systems.

Animals↗
PubMed1997

Peroxisome proliferator-activated receptor gamma and the control of adipogenesis.

The adipose cell is now known to play a complex role in energy homeostasis, storing energy and signaling to other tissues concerning the state of energy balance. The past several years have seen an explosive increase in our knowledge of the transcriptional basis of adipocyte differentiation. This review describes the role of peroxisome proliferator-activated receptor gamma in this process, and describes how other transcription factors may affect adipogenesis by modulating the amount or activity of peroxisome proliferator-activated receptor gamma. Furthermore, peroxisome proliferator-activated receptor gamma and other adipogenic transcription factors provide a focus for beginning to understand how various hormones and metabolites influence the development of this tissue in vivo.

Adipose Tissue↗
PubMed1997

Cationic colloidal gold staining of acidic glycoconjugates in mouse Paneth cells.

The acidic glycoconjugates of mouse ileum Paneth cells were examined with the aid of light and electron microscopy, using cationic colloidal gold (CCG) as a probe. Specimens of mouse ilea were fixed in half-strength Karnovsky's fixative and embedded in Lowicryl K4M resin. Semithin and ultrathin sections were cut of examination with light and electron microscopy, respectively. Examination of the sections using light microscopy revealed the positive staining of CCG at pH 1.0 and pH 2.5, which was detected at the rim of secretory granules and at the supranuclear regions of the Paneth cells. At pH 4.0, in addition to staining of the secretory granule rim, weak staining was observed in the granule core. At pH 7.2, the cytoplasm other than secretory granules exhibited positive CCG staining. Examination of the sections using electron microscopy, at pH 1.0, the trans lamellae of the Golgi apparatus, the rim of the secretory granules, and lysosomes were labeled selectively by CCG. At pH 2.5, labeling was also discernible over the same structures in the cells. However, at this pH, the labeling intensity was stronger than that at pH 1.0, due to the dual labeling of sulfated and sialylated glycoconjugates in these structures. At pH 4.0, the Golgi apparatus, rims and cores of secretory granules and ribosomes were labeled. Lysosomes and nuclei were also positively stained. At pH 7.2, the rims of secretory granules were not stained. The present results indicate that the CCG method gives good resolution and contrast when applied to staining, and therefore is useful for the specific staining of glycoconjugates such as sulfated, sialylated and phosphated glycoconjugates for light and electron microscopy.

Animals↗
PubMed1996

Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARgamma.

Adipocyte differentiation is an important component of obesity and other metabolic diseases. This process is strongly inhibited by many mitogens and oncogenes. Several growth factors that inhibit fat cell differentiation caused mitogen-activated protein (MAP) kinase-mediated phosphorylation of the dominant adipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) and reduction of its transcriptional activity. Expression of PPARgamma with a nonphosphorylatable mutation at this site (serine-112) yielded cells with increased sensitivity to ligand-induced adipogenesis and resistance to inhibition of differentiation by mitogens. These results indicate that covalent modification of PPARgamma by serum and growth factors is a major regulator of the balance between cell growth and differentiation in the adipose cell lineage.

3T3 Cells↗
PubMed1996

Developmental expression of 'RZR beta, a putative nuclear-melatonin receptor' mRNA in the suprachiasmatic nucleus of the rat.

RZR beta is a member of the retinoid Z receptor (RZR) family of orphan receptors, and its expression is brain-specific. Recently, it was reported that the distribution of RZR beta mRNA is partially coincident with melatonin binding sites and that RZR beta is a putative nuclear receptor of melatonin. Using in situ hybridization, we investigated the developmental expression of RZR beta mRNA in the suprachiasmatic nucleus (SCN) of the rat, which is considered as circadian pacemaker. The RZR beta mRNA was first found in the dorsomedial portion of the SCN at embryonic day 20, and RZR beta mRNA expression in the dorsomedial SCN continued until postnatal day 60. This result suggests that RZR beta plays specific roles as a transcription factor in the dorsomedial SCN but not in the ventrolateral SCN during development and throughout postnatal life.

Animals↗
PubMed1996

ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism.

Adipocyte determination and differentiation-dependent factor 1 (ADD1) is a member of the basic helix-loop-helix leucine zipper (bHLH-LZ) family of transcription factors that binds to two distinct DNA sequences and has been associated with both adipocyte development and cholesterol homeostasis (where it has been termed SREBP1). To investigate the biological role of ADD1, we expressed wild-type and dominant negative forms of this protein with retroviral vectors in preadipocytes and nonadipogenic cells. A dominant-negative form of ADD1 with a point mutation in the DNA-binding domain sharply represses the differentiation of 3T3-L1 cells as observed morphologically or by the expression of adipocyte-specific mRNAs. When NIH-3T3 cells ectopically expressing ADD1 are cultured under hormonal conditions not favoring differentiation, they do not overtly differentiate but still activate expression of mRNAs for fatty acid synthase (FAS) and lipoprotein lipase (LPL), two key genes that regulate fatty acid metabolism. Under culture conditions permissive for differentiation including a PPAR activator, 15%-20% of the cells expressing ADD1 undergo adipogenesis while 2%-3% of cells containing a control vector differentiate. Simultaneous expression of ADD1 with PPARgamma increases the transcriptional activity of this adipogenic nuclear hormone receptor, suggesting involvement of ADD1 in this pathway. These data indicate that ADD1 plays an important role in fat cell gene expression and differentiation, and suggest that it may function by augmenting a step in PPARgamma-mediated transcription.

3T3 Cells↗
PubMed1996

Postembryonic neurogenesis in the central nervous system of the tobacco hornworm, Manduca sexta. III. Spatial and temporal patterns of proliferation.

Postembryonic neurogenesis leads to a dramatic increase in the number of functional neurons within the segmental ganglia of the moth, Manduca sexta. These adult-specific neurons are generated during larval life by segment-specific arrays of individually identifiable stem cells, or neuroblasts (Nbs). By the end of the feeding larval stage, each Nb has generated a discrete nest of progeny, which ranges in size from less than 10 to more than 70 progeny. The sizes of these identifiable nests of progeny vary in a segment-specific manner, with the thoracic nests containing a greater number of progeny compared with their homologues in the simpler abdominal ganglia. In order to describe those factors that influence the size of the post-embryonic neuronal lineages, we examined the spatial and temporal pattern of postembryonic neurogenesis in the segmental ganglia of Manduca. The rates at which the identifiable nests accumulated progeny were estimated by counting the number of progeny within the nests, using sectioned material isolated from animals at stages ranging from embryonic hatching until the end of the feeding larval stage. All of the postembryonic Nbs began to generate progeny at around the time of the molt to the third larval instar. Each nest added progeny at a rate that was a characteristic of its identity and segment of origin. Although all of the nests within the thorax continued to accumulate progeny throughout the feeding larval stage, several of the abdominal nests showed little or no growth following the molt to the fifth larval instar. The thymidine analog 5-bromo 2-deoxyuridine (5-BrdU) was used to estimate the mitotic rates of the identifiable Nbs. The number of labeled progeny within a nest 24 h after application of 5-BrdU ranged from a low of 1 to 2 to a high of 11 to 13 labeled cells. In some instances there was a good correlation between the estimated mitotic rate of an identified Nb and the rate of growth of its associated nest of progeny. However, several of the identifiable nests accumulated progeny at a slower rate than predicted based on the estimated mitotic rate of the Nb. Cell death appears to be responsible for slowing the growth of the nests during the feeding larval stage. We estimate that 10% to 70% of the neurons generated during the feeding larval stage degenerate within 24 h of their birth. The level of cell death observed within a nest was dependent on both its identity and its segment of origin.

Animals↗
PubMed1996

Improved lipid-mediated gene transfer into primary cultures of hippocampal neurons.

We have examined lipids as transfection agents to introduce recombinant plasmids into primary cultures of rat hippocampal neurons. By modifying the protocol for transfection mediated by the commercial reagent DOTAP, we were able to achieve a transfection efficiency of about 3%. Expression of various transfected gene products was sustained for several weeks in culture, the neurons developed normally and the transfected gene products were targeted to the appropriate subcellular compartment.

Animals↗
PubMed1996

Adipocyte differentiation: a transcriptional regulatory cascade.

The adipose cell is now known to play a complex role in energy homeostasis, energy storage and signaling to other tissues concerning the state of energy balance. The past few years have seen an explosive increase in our knowledge of the transcriptional basis of adipocyte differentiation. Factors such as peroxisome proliferator-activated receptor gamma, the CCAAT/enhancer binding protein family members, and adipocyte determination- and differentiation-dependent factor 1 play important regulatory roles in this process. Furthermore, these factors provide a focus for beginning to understand how various hormones and metabolites influence the development of adipose tissue in vivo.

Adipocytes↗
PubMed1996

Detection of antibodies to human melanoma cells in vitiligo and alopecia areata by Western blot analysis.

Antibody reactivity to human melanoma cells (SK-Mel-23) was investigated in 48 patients with vitiligo, 14 with alopecia areata (AA), and 35 normal control individuals by Western blot analysis. Antibodies to SK-Mel-23 were found in 44 (92%) of the patients with vitiligo, in 7 (50%) of the patients with AA, and in 14 (40%) of the normal control individuals. Significant differences between patients with vitiligo and normal controls were found in the incidence and distribution of antibodies, but no significant differences were found between patients with AA and normal controls. The antibodies were predominantly directed to one or more antigens of approximately 110 KD, 103 KD, 88 KD, 70 KD, 56 KD, 46 DK, or 41 KD. The most common responses were to 110 KD, 88KD, and 70 KD antigens. These antibodies were present in 60%, 60%, and 73% of the patients with vitiligo; 7%, 14% and 35% of the patients with AA; and 11%, 11% and 40% of normal control individuals, respectively. There were no statistical differences in the incidence of antibodies to pigment cells between segmental and non-segmental vitiligo. These findings suggest that autoreactivity to pigment cells occurs mostly in patients with vitiligo and might be a secondary immune reaction to destroyed pigment cells.

Alopecia Areata↗
PubMed1995

Inhibitory effect of Korean mistletoe (Viscum album coloratum) extract on tumour angiogenesis and metastasis of haematogenous and non-haematogenous tumour cells in mice.

We examined the inhibitory effect of an aqueous extract (referred to as KM-110) from Viscum album coloratum, a Korean mistletoe, on tumour metastasis produced by highly metastatic murine tumour cells, B16-BL6 melanoma, colon 26-M3.1 carcinoma and L5178Y-ML25 lymphoma cells, using experimental and spontaneous metastasis models in syngeneic mice. In experimental metastasis of B16-BL6 and colon 26-M3.1 cells, intravenous (i.v.) administration of KM-110 (100 micrograms/mouse) 1 day after tumour inoculation significantly inhibited lung metastasis of both tumour cells. The administration of KM-110 also exhibited a therapeutic effect on liver and spleen metastasis of L5178Y-ML25 lymphoma cells. Furthermore, in spontaneous metastasis of B16-BL6 melanoma cells, multiple administration of KM-110 into tumour-bearing mice resulted in significant inhibition of lung metastasis by tumour cells, as well as the suppressive activity to the growth of primary tumour. In in vivo analysis for tumour-induced angiogenesis, the i.v. administration of KM-110 suppressed tumour growth and inhibited the number of blood vessels oriented towards the tumour mass. In a bioassay, the culture supernatant (KM-110-treated medium) of murine peritoneal macrophages that had been stimulated with KM-110 (1-10 micrograms/ml) for 30 min followed by 24 h incubation in fresh medium showed a strong tumour necrosis factor-alpha (TNF-alpha) activity. In addition, KM-110-treated medium significantly inhibited the growth of in vitro cultures of rat lung endothelial (RLE) cells. These results suggested that the extract of Korean mistletoe inhibits tumour metastasis caused by haematogenous as well as non-haematogenous tumour cells, and that its antimetastatic effect results from the suppression of tumour growth and the inhibition of tumour-induced angiogenesis by inducing TNF-alpha.

Animals↗