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Biomedical subjects

S Kang

Publications and source records attributed to S Kang.

At least 127 records · Page 7Linked to original sources
PubMed1998

[The comparison of biological characteristics between tumor-infiltrating lymphocytes and tumor-associated lymphocytes in ascites of epithelial ovarian carcinoma].

OBJECTIVE: To compare biological charicteristics between tumor-infiltrating lymphocytes (TIL) and tumor-associated lymphocytes (TAL) in epithelial ovarian carcinomas. METHODS: The surgical samples of four ovarian specimens and eight cancer ascites from epithelial ovarian carcinoma were collected, and ascites were divided into bloody and non-bloody groups. The cancer tissue was dissected to yield single cells suspensions. TIL and TAL were grown in coculture with autologous tumor cells and 500 U/ml recombinant interleukin-2 (rIL-2). Phenotype was studied using flow cytometry for a varity of human immunocompetent cell surface markers (CD3, CD4, CD8, CD25). Cytotoxicity was investigated using 4-hr 51Cr-release assays with primary ovarian carcinoma cell cultures and the CAOV3 cell line and the K562 cell line as target cells in cultured period. RESULTS: (1) There was no significant difference in CD3, CD4, CD8 and CD25 expression among the three groups (P > 0.05). CD4 to CD8 (CD4/CD8) ratio was consistently more than 1 in cultured period. (2) In all three groups, Natural killer (NK) acitivity was high and no difference among them (P > 0.05). (3) In all twelve cases, TIL and TAL in the non-bloody ascites possess higher potential to lyse the autologous tumor target than TAL in the bloody ascites (P < 0.01) when effector cell to target cell (E:T) was 50 to 1 (50:1). Lytic activity was 30.2%-51.0% and 10.8%-15.8% respectively. CONCLUSIONS: TIL and TAL in non-bloody ascites in epithelial ovarian cancer have the same biological characteristics.

Ascitic Fluid↗
PubMed1998

[Effect of electroacupuncture on succinate dehydrogenase of gentamycin induced ototoxic cochlear hair cells in guinea pigs].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on succinate dehydrogenase (SDH) of gentamycin (GE) induced ototoxic cochlear hair cells. METHODS: Preyer's reflex normal guinea pigs were selected and divided randomly into three groups: GE group, EA group, control group. Brainstem auditory evoked potential (BAEP) and SDH in the cochlear hair cells were taken as indexes. In the animals of GE group GE was alone injected intramuscularly 80 mg.kg-1.d-1 for 20 days, while in the animals of EA group GE and additional EA was applied once a day on Tinggong (SI19), Yifeng(SJ17) and Shenshu (UB23) points. EA lasted for 15 minutes. RESULTS: In the GE group BAEP reaction threshold rose markedly, while that rose slightly in EA group. The difference was significant between two groups (P < 0.05). The change of SDH within cochlear hair cells and degree of hair cells injury in the EA group were lower than those in GE group. CONCLUSIONS: EA therapy could relieve GE ototoxicity, protect SDH in cochlear hair cells and might be a possible mechanism of action of EA.

Animals↗
PubMed1998

[The effects of jianpizengmian granule on tumor growth and immune function].

The effects of Jianpizengmian (JPZM) granule on tumor growth and immune function were researched in tumor-bearing mice. The results showed it had significant inhibiting activity against S180 and HePA by oral JPZM. The inhibitory rate of JPZM reached 46.25% and 45.57%. JPZM could markedly increase the index of spleen and thymus, the level of serum hemolysin and the spleen lymphocytes transformation in tumor-bearing mice, compared to control group (H2O) respectively.

Animals↗
PubMed1998

The HIV type 1 coreceptor CCR5 and its role in viral transmission and disease progression.

The purified CD4+ lymphocytes of a group of highly exposed but HIV-1-uninfected individuals were determined to be less susceptible to infection with multiple non-syncytium-inducing (NSI) primary isolates of HIV-1 than were CD4+ lymphocytes from nonexposed control individuals. This relative resistance to HIV-1 infection did not extend to T cell line-adapted or syncytium-inducing (SI) primary viral isolates, was restricted by the envelope glycoprotein, and was associated with an increased production of the C-C chemokines RANTES, MIP-1alpha, and MIP-1beta. The block to replication in CD4+ lymphocytes from two exposed-uninfected subjects was at the point of entry, as was the block imposed by the recombinant C-C chemokines RANTES, MIP-1alpha, and MIP-1beta. Resistance to infection and the high production of beta chemokines were characteristic of every CD4+ lymphocyte clone from the exposed-uninfected subjects. We have now identified the mechanism underlying this in vitro and in vivo resistance to infection: These individuals have inherited a homozygous 32-bp nucleotide deletion (delta32) within the gene encoding the coreceptor for primary NSI isolates of HIV-1 (CCR5). This deletion encodes a severely truncated and unstable protein that is not expressed on the cell surface. This allele is common in the Caucasian population, with a frequency of 0.0808, but is not found in people of African or Asian ancestry. To determine its role in HIV-1 transmission and disease progression, we analyzed the CCR5 genotype of 1252 homosexual men enrolled in the Chicago component of the Multicenter AIDS Cohort Study (MACS). No infected participant was found to be homozygous for the delta32 allele whereas 3.6% of at-risk but uninfected Caucasian participants were homozygous, showing the highly protective role of this genotype against sexual acquisition of HIV-1. No evidence was found to suggest that heterozygotes were protected against HIV-1 infection, but a limited protective role against disease progression was noted. The delta32 allele of CCR5 is therefore an important host factor in HIV-1 transmission and pathogenesis.

CD4-Positive T-Lymphocytes↗
PubMed1998

Molecular mechanisms of intrinsic skin aging and retinoid-induced repair and reversal.

Past studies have shown that topical treatment of sun-exposed skin with all-trans retinoic acid improves the clinical and histologic appearance of the skin. This is associated with a reduction in matrix metalloproteinase elaboration and with expression of a newly synthesized collagenous matrix. Whether retinoid therapy might have a similar impact on the appearance of intrinsically aged skin is not known. This study, using human skin in organ culture and epidermal keratinocytes and fibroblasts in monolayer culture, show that retinoic acid stimulates growth of both keratinocytes and fibroblasts and stimulates extracellular matrix production by the fibroblasts. Adult skin from sun-exposed and sun-protected sites responds equally well to retinoic acid, whereas neonatal skin is much less responsive under the same conditions. The implications of this are (i) that retinoids may be able to repair intrinsically aged skin as well as photoaged skin, and (ii) that retinoids modulate human skin cell function in a manner that is age-related, and not simply a response to photodamage.

Adult↗
PubMed1997

Pathophysiology of premature skin aging induced by ultraviolet light.

BACKGROUND: Long-term exposure to ultraviolet irradiation from sunlight causes premature skin aging (photoaging), characterized in part by wrinkles, altered pigmentation, and loss of skin tone. Photoaged skin displays prominent alterations in the collagenous extracellular matrix of connective tissue. We investigated the role of matrix-degrading metalloproteinases, a family of proteolytic enzymes, as mediators of collagen damage in photoaging. METHODS: We studied 59 whites (33 men and 26 women, ranging in age from 21 to 58 years) with light-to-moderate skin pigmentation, none of whom had current or prior skin disease. Only some of the participants were included in each of the studies. We irradiated their buttock skin with fluorescent ultraviolet lights under standard conditions and obtained skin samples from irradiated and nonirradiated areas by keratome or punch biopsy. In some studies, tretinoin and its vehicle were applied to skin under occlusion 48 hours before ultraviolet irradiation. The expression of matrix metalloproteinases was determined by in situ hybridization, immunohistology, and in situ zymography. Irradiation-induced degradation of skin collagen was measured by radioimmunoassay of soluble cross-linked telopeptides. The protein level of tissue inhibitor of matrix metalloproteinases type 1 was determined by Western blot analysis. RESULTS: A single exposure to ultraviolet irradiation increased the expression of three matrix metalloproteinases -- collagenase, a 92-kd gelatinase, and stromelysin -- in skin connective tissue and outer skin layers, as compared with nonirradiated skin. The degradation of endogenous type I collagen fibrils was increased by 58 percent in irradiated skin, as compared with nonirradiated skin. Collagenase and gelatinase activity remained maximally elevated (4.4 and 2.3 times, respectively) for seven days with four exposures to ultraviolet irradiation, delivered at two-day intervals, as compared with base-line levels. Pretreatment of skin with tretinoin (all-trans-retinoic acid) inhibited the induction of matrix metalloproteinase proteins and activity (by 70 to 80 percent) in both connective tissue and outer layers of irradiated skin. Ultraviolet irradiation also induced tissue inhibitor of matrix metalloproteinases-1, which regulates the enzyme. Induction of the inhibitor was not affected by tretinoin. CONCLUSIONS: Multiple exposures to ultraviolet irradiation lead to sustained elevations of matrix metalloproteinases that degrade skin collagen and may contribute to photoaging. Treatment with topical tretinoin inhibits irradiation-induced matrix metalloproteinases but not their endogenous inhibitor.

Administration, Cutaneous↗
PubMed1997

Flexible DNA: genetically unstable CTG.CAG and CGG.CCG from human hereditary neuromuscular disease genes.

The properties of duplex CTG.CAG and CGG.CCG, which are involved in the etiology of several hereditary neurodegenerative diseases, were investigated by a variety of methods, including circularization kinetics, apparent helical repeat determination, and polyacrylamide gel electrophoresis. The bending moduli were 1.13 x 10(-19) erg.cm for CTG and 1.27 x 10(-19) erg.cm for CGG, approximately 40% less than for random B-DNA. Also, the persistence lengths of the triplet repeat sequences were approximately 60% the value for random B-DNA. However, the torsional moduli and the helical repeats were 2.3 x 10(-19) erg.cm and 10.4 base pairs (bp)/turn for CTG and 2.4 x 10(-19) erg.cm and 10.3 bp/turn for CGG, respectively, all within the range for random B-DNA. Determination of the apparent helical repeat by the band shift assay indicated that the writhe of the repeats was different from that of random B-DNA. In addition, molecules of 224-245 bp in length (64-71 triplet repeats) were able to form topological isomers upon cyclization. The low bending moduli are consistent with predictions from crystallographic variations in slide, roll, and tilt. No unpaired bases or non-B-DNA structures could be detected by chemical and enzymatic probe analyses, two-dimensional agarose gel electrophoresis, and immunological studies. Hence, CTG and CGG are more flexible and highly writhed than random B-DNA and thus would be expected to act as sinks for the accumulation of superhelical density.

DNA↗
PubMed1997

Rapamycin (sirolimus) inhibits proliferating cell nuclear antigen expression and blocks cell cycle in the G1 phase in human keratinocyte stem cells.

Because the immunosuppressant rapamycin (sirolimus) blocks T cell proliferation in G1 phase, it has been proposed as a potential treatment for psoriasis, a skin disease characterized by T cell activation and keratinocyte stem cell hyperproliferation. To determine another potentially important mechanism through which rapamycin can act as an antipsoriatic agent, we tested its direct effect on keratinocyte stem cell proliferation in vitro as well as in vivo. In vivo cell cycle quiescent (G0 phase) stem cell keratinocytes in primary culture sequentially express de novo cyclin D1 and proliferating cell nuclear antigen (PCNA), prior to S phase entry, and upregulate beta1 integrin. Rapamycin inhibited the growth of keratinocytes that were leaving quiescence as well as those already in cell cycle without affecting cell viability. Although beta1 integrin(bright) expression was not affected, the number of beta1 integrin(bright) cells entering S/G2/M was significantly lowered by rapamycin. Cells treated with rapamycin exhibited decreased PCNA expression while cyclin D1 expression, which precedes PCNA expression in the cell cycle, was not affected. We found similar effects on stem cell keratinocytes in patients with psoriasis treated systemically with rapamycin. Because PCNA is required for cell cycle progression from G1 to S phase, our data indicate that inhibition of PCNA protein synthesis may be an important regulatory element in the ability of rapamycin to exert a G1 block.

Cells, Cultured↗
PubMed1997

Identification of in vivo phosphorylation sites of CD45 protein-tyrosine phosphatase in 70Z/3.12 cells.

Phosphorylation of CD45, a transmembrane protein-tyrosine phosphatase (PTPase), has been proposed to mediate docking of signaling proteins and to modulate PTPase activity. To study the role of phosphorylation in CD45, in vivo phosphorylation sites of CD45 from 70Z/3.12 cells were identified using 32P labeling, trypsin digestion, two-dimensional peptide mapping, high performance liquid chromatography, phosphoamino acid analysis, matrix-assisted laser desorption/ionization mass spectrometry, and specific enzymatic degradation. Eight phosphopeptides, a through h, were isolated and four phosphorylation sites were identified. All four phosphorylation sites were in the membrane-distal PTPase domain (D2) and the C-terminal tail and none were in the membrane-proximal PTPase domain (D1). One site, Ser(P)939 peptide h, was in the D2 domain and, by comparison to the three-dimensional structure of PTP1B, is predicted to lie at the apex of the substrate binding loop. Ser939 was the only in vitro phosphorylation site for protein kinase C among the phosphorylation sites identified. Four of the C-terminal peptides identified (d, e, f, and g) spanned the same sequence and were derived from the same phosphorylation site in the C-terminal tail, Ser1204. Peptide a was derived from the intact C terminus and comprised a mixture of monophosphorylated peptides containing either Ser(P)1248 or Thr(P)1246. Knowledge of the precise phosphorylation sites of CD45 will lead to the design of experiments to define the role of phosphorylation in PTPase activity and in signaling.

Amino Acid Sequence↗
PubMed1997

Expressed sequences from conidial, mycelial, and sexual stages of Neurospora crassa.

In the Neurospora Genome Project at the University of New Mexico, expressed sequence tags (ESTs) corresponding to three stages of the life cycle of the filamentous fungus Neurospora crassa are being analyzed. The results of a pilot project to identify expressed genes and determine their patterns of expression are presented. 1,865 partial complementary DNA (cDNA) sequences for 1,409 clones were determined using single-pass sequencing. Contig analysis allowed the identification of 838 unique ESTs and 156 ESTs present in multiple cDNA clones. For about 34% of the sequences, highly or moderately significant matches to sequences (of known and unknown function) in the NCBI database were detected. Approximately 56% of the ESTs showed no similarity to previously identified genes. Among genes with assigned function, about 43.3% were involved in metabolism, 32.9% in protein synthesis and 8.4% in RNA synthesis. Fewer were involved in defense (6%), cell signalling (3.4%), cell structure (3.4%) and cell division (2.6%).

Amino Acid Sequence↗
PubMed1997

Sudden unilateral blindness after intracranial aneurysm surgery.

The incidence of unilateral blindness and ophthalmoplegia after aneurysm surgery is very rare, but if it occurs, it is mainly caused by intra-operative nerve injury. We experienced 6 cases of unilateral blindness immediately after surgery for 3 recent years. These patients were classified into Hunt-Hess grade I to II except for one patient with III. All patients complained of visual loss with varying degree of lid oedema and ophthalmoplegia ipsilateral to the site of surgery. Angiographic examination of these patients revealed that the aneurysm was located at the internal carotid artery bifurcation in one case and the middle cerebral artery bifurcation in five cases. All of them were relatively far from the optic nerve. The aneurysm was clipped easily with minimal brain retraction via standard pterional craniotomy since the brain was slack in all cases. In all cases, injuring the optic nerve during surgery was remote. All patients showed evidence of retinal ischaemia on fundoscopy with or without fluorescein angiography. The pathophysiology of this ischaemic event is unknown. In our patients, we could exclude possible aetiological factors such as abnormal systemic and ocular conditions, causing ischaemia in intra-orbital structures, increased intracranial pressure, intra-operative hypotension, carotid atherosclerosis, and ocular vasospasm etc. Accordingly we speculate that the complications seen in our cases were most likely related to intra-orbital ischaemia initiated by a collapse of the arterial and venous channels in the orbit and/or to direct or indirect contusion on the intra-orbital structures. These situations could be produced by inadvertent pressure placed on the eyeball with a bulky retracted frontal skin flap. Visual acuity in these patients ranged from no light perception to the ability to see objects and detect colour. Their conditions were irreversible. The degree of visual recovery seems to be dependent on the duration and severity of retinal ischaemia by orbital compression. Unfortunately there is no satisfactory treatment. We recommend the use of an eye shield to protect ipsilateral eyeball just before aneurysm surgery.

Adult↗
PubMed1997

Gene structure and allelic expression assay of the human GLI3 gene.

The GLI3 gene encodes a putative zinc finger transcription factor that is important in early vertebrate development. Haploinsufficiency of this gene has been associated with the Greig cephalopolysyndactyly syndrome and truncation mutations cause Pallister-Hall syndrome. In the course of studies to determine the etiology of Pallister-Hall syndrome, we required knowledge of the fine structure of GLI3 to perform detailed genetic and physical mapping and mutation screening of this gene. The coding region of GLI3 is composed of 14 exons, including a large exon of more than 2500 bp. In addition, the gene contains two intragenic dinucleotide repeats, and four single-base pair polymorphisms in the coding region. We have used these coding region polymorphisms to design an allele-specific expression study that will be useful for studying patients with Greig cephalopolysyndactyly syndrome. In addition, GLI3 should be considered a candidate gene for related developmental anomalies of humans. Such hypotheses will be more readily addressed with the availability of the fine structure of the gene and the allele-expression assay.

Abnormalities, Multiple↗
PubMed1997

Mucinous carcinoma of the skin.

Primary mucinous carcinoma of the skin is a rare adnexal neoplasm with sweat gland differentiation. We describe a case of primary mucinous carcinoma of the skin and characterize its clinical and histologic features. Mucinous carcinoma can occur in noncutaneous visceral sites and may metastasize to the skin. Thus it is important to exclude the possibility of a noncutaneous visceral primary tumor before diagnosing primary mucinous carcinoma of the skin.

Adenocarcinoma, Mucinous↗
PubMed1997

Effect of pulsatile pressure on the breaking strength and movement of Prolene sutures.

PURPOSE: Most studies of sutures used in vascular surgery have used steadily applied loads. But in vivo, sutures are subject to pulsatile pressures. Pulsatile pressures could weaken sutures, or they could be beneficial by helping to slide the suture, thereby equilibrating the tension between unevenly tightened loops. This study examined the effect of pulsatile pressures on the strength and movement of polypropylene (Prolene) sutures. METHODS: Segments of pig thoracic aorta were cannulated and studied in a tissue bath in vitro at 37 degrees C. A longitudinal arteriotomy was made and then closed with running 6-0 Prolene. Vessels were subjected to (1) no pressure; (2) 100 mm Hg steady pressure; or (3) 112/65 mm Hg pulsatile pressure. After 48 hours the sutures were studied for breaking strength. In a second, separate set of experiments, longitudinal arteriotomies were closed using running suture lines. These were constructed with either several loose loops or several overly tight loops. Fine wires were affixed to the suture loops to permit photographic recording of suture movement. RESULTS: There was no difference in breaking force among 68 sutures that had been subjected to (1) no pressure; (2) 100 mm Hg steady pressure; or (3) 112/65 mm Hg pulsatile pressure. These also were no different than sutures that were not sewn into arteries. These findings indicate that neither steady nor pulsatile pressures weaken Prolene sutures. In the second set of experiments, it was found that pulsatile pressure did cause movement of suture lines where there were loose loops (p < 0.05). However, neither steady nor pulsatile pressures caused movement of loops in suture lines that contained normal and overly tight loops. CONCLUSIONS: Neither steady nor pulsatile physiologic pressures weaken 6-0 Prolene sutures that have been used to close a longitudinal arteriotomy. These pressures can cause movement of loose suture lines, but do not equilibrate the tension between normal and overly tight suture loops. Overly tight loops may place excessive load on a suture line.

Blood Pressure↗
PubMed1997

GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome.

Pallister-Hall syndrome (PHS, M146510) was first described in 1980 in six newborns. It is a pleiotropic disorder of human development that comprises hypothalamic hamartoma, central polydactyly, and other malformations. This disorder is inherited as an autosomal dominant trait and has been mapped to 7p13 (S. Kang et al. Autosomal dominant Pallister-Hall syndrome maps to 7p13. Am. J. Hum. Genet. 59, A81 (1996)), co-localizing the PHS locus and the GLI3 zinc finger transcription factor gene. Large deletions or translocations resulting in haploinsufficiency of the GLI3 gene have been associated with Greig cephalopolysyndactyly syndrome (GCPS; M175700) although no mutations have been identified in GCPS patients with normal karyotypes. Both PHS and GCPS have polysyndactyly, abnormal craniofacial features and are inherited in an autosomal dominant pattern, but they are clinically distinct. The polydactyly of GCPS is commonly preaxial and that of PHS is typically central or postaxial. No reported cases of GCPS have hypothalamic hamartoma and PHS does not cause hypertelorism or broadening of the nasal root or forehead. The co-localization of the loci for PHS and GCPS led us to investigate GLI3 as a candidate gene for PHS. Herein we report two PHS families with frameshift mutations in GLI3 that are 3' of the zinc finger-encoding domains, including one family with a de novo mutation. These data implicate mutations in GLI3 as the cause of autosomal dominant PHS, and suggest that frameshift mutations of the GLI3 transcription factor gene can alter the development of multiple organ systems in vertebrates.

Abnormalities, Multiple↗
PubMed1997

The transcriptional repression of the human Cu/Zn superoxide dismutase(sod1) gene by the anticancer drug, mitomycin C(MMC).

The Cu/Zn superoxide dismutase(sod1) is one of the key enzymes that protects cells against oxidative stress. In order to investigate the effects of mitomycin C(MMC) on the induction of apoptotic cell death and on the sod1 transcription level, the CATs activity of HepG2 cells transfected with sod1 promoter-CAT(chloramphenicol acetyl transferase) fusion reporter was measured after MMC treatment. The CAT assay showed that exposure of HepG2 cells to MMC decreased the transcription level of the sod1 gene. The accumulation of p53 tumor suppressor protein by MMC treatment of HepG2 cells was noted. In order to investigate the p53-negative response element in its promoter region, a p53 cotransfection experiment with serially deleted sod1 promoter/CAT reporter constructs was performed. The results show a significant reduction of CAT activity in all deletion reporter constructs. The results show that MMC treatment inhibited sod1 gene transcription through p53-mediated transcriptional repression.

Antibiotics, Antineoplastic↗
PubMed1997

Activation of ribosomal protein S6 kinase in psoriatic lesions and cultured human keratinocytes by epidermal growth factor receptor ligands.

p70 Ribosomal protein S6 kinase is a critical down-stream effector of a mitogen-stimulated signaling pathway that is selectively inhibited by the immunosuppressant rapamycin. The purpose of this study was to quantify S6 kinase expression in psoriatic involved, uninvolved, and normal epidermis and to characterize regulation of S6 kinase activity in cultured normal human keratinocytes. S6 kinase activity was increased 4-fold in psoriatic lesions (1.63 +/- 0.25 pmol per min per mg, n = 6), compared to nonlesional (0.44 +/- 0.12 pmol per min per mg, n = 6, p < 0.01), and normal (0.35 +/- 0.14 pmol per min per mg, n = 7, p < 0.01) epidermis. In contrast, S6 kinase mRNA and protein levels were not significantly different among psoriatic lesional, nonlesional, and normal epidermis. In keratinocytes, S6 kinase activity was stimulated 3-fold by mitogenic epidermal growth factor (EGF) receptor ligands, EGF and transforming growth factor-alpha (TGF-alpha), but not by cytokines interleukin-1alpha, tumor necrosis factor-alpha, interferon-gamma, or transforming growth factor-beta1. TGF-alpha stimulation of S6 kinase activity was inhibited in a concentration-dependent manner by rapamycin (IC50 < 0.2 nM) and the specific EGF receptor antagonist PD153035 (IC50 = 20 nM). Rapamycin also inhibited EGF-stimulated proliferation of keratinocytes (IC50 = 0.2 ng per ml) with a potency similar to that reported for inhibition of T-cell proliferation. We conclude: (i) the mitogenic signaling pathway(s) regulating S6 kinase is activated in psoriatic lesions, thus accounting for increased S6 kinase activity in the absence of increased S6 kinase gene or protein expression; (ii) S6 kinase activation in lesional keratinocytes likely occurs in response to EGF receptor stimulation by TGF-alpha and/or amphiregulin, which are known to be elevated in psoriatic lesions; and (iii) keratinocyte as well as T-cell mitogenic signaling pathways are susceptible to inhibition by rapamycin, suggesting that rapamycin may be of therapeutic benefit in the treatment of psoriasis.

Adult↗