Biomedical subjects
Publications and source records attributed to S Kang.
Four families highly clustered for extreme longevity are described here, representing the first report of clustering for this phenotype. Families such as these may prove to be helpful in the further understanding of the genetic contribution to achieving exceptional longevity.
The effects of different soil moistures and shading levels on stomatal conductance(Gs), net photosynthetic rates(Pn), transpiration and leaf water potential(LWP) of cotton (variety Zhongmian No. 23) grown in pots from the seedling to flower bud stages in summer noon were evaluated. We designed three shading levels: no-shading(CK), 75% shading (DN), 40% shading(SN); and three soil moistures; 85%-100% (high water, HW), 65%-85% (medium water, MW) and 45%-65% (low water, LW) of field water-bolding capacity. The Gs of DN and SN increased by 16.69% and 28.01% compared with CK at HW, respectively, while the Pn of DN and SN declined by 45.74% and 20.54%, respectively. The Gs of DN and SN enhanced by 28.86% and 23.28% compareds with CK at MW, respectively, while the Pn of DN and SN decreased by 31.97% and 1.64%, respectively. The Gs of CK, DN and Sn did not exhibit significant differences at LW, while Pn of DN and SN reduced by 46.22% and 13.45%, respectively. Significant difference in Gs did not exist between DN and SN at the same soil moisture, but there was significant difference in Pa between them (except at LW). It was suggested that Gs declined with the increasing of leaf-to-air vapor pressure difference (VPD) and showed weak correlation with Pn by regression. The combined effects of soil moistures and shading levels on LWP and transpiration rate were not significant. There was no significant difference in LWP and transpiration rate among three shading treatments. Contrasted to treatment CK, intercellular CO2 concentration (Ci) in DN and SN at HW, MW and LW increased significantly, except no apparent change of Ci in SN at MW.
OBJECTIVE: To investigate the early recognition and management of acute fatty liver of pregnancy (AFLP) to improve maternal and fetal survival. METHODS: Eight cases of AFLP seen in our hospital during the past three years were studied retrospectively. Symptoms, laboratory findings, timing of liver biopsy, and maternal and fetus outcome were assessed. RESULTS: The mean gestational age at onset was 34 +/- 2 weeks. All cases were primigravida. In the early stages, all patients presented malaise, nausea, vomiting and epigastric distress followed by jaundice in the third trimester of pregnancy. LABORATORY FINDINGS: all had raised transaminases and serum bilirubin (32.5-510.8 mumol/L), hypoalbuminemia (22.4-30.0 g/L), hypofibrinogenemia (< 180 mg/dl), prolonged prothrombin time and prolonged partial thromboplastin time. Maternal complication included hepatic encephalopathy (6 cases), ascites (6), hypoglycemia (5), hematemesis (2), and postpartum hemorrhage (5) and preeclampsia (4). Emergency cesarean section was performed in 3 cases. One mother died of fulminant hepatic failure and the others survived. There was no fetus death. Liver biopsy was done on the 5th to 15th postpartum day in 8 cases. CONCLUSION: With increasing awareness, especially in the early recognition of milder cases, and prompt progressive management including early termination of pregnancy by cesarean section and large dose infusion of fresh frozen plasma and albumin alternately, the prognosis of AFLP can be improved.
Lipase of Staphylococcus haemolyticus L62 was purified from culture supernatant and its molecular mass was estimated to be 45 kDa by SDS-PAGE. Its optimum temperature and pH for the hydrolysis of olive oil was 28 degrees C and pH 8.5, respectively. The enzyme was stable up to 50 degrees C in the presence of Ca(2+)and over the pH range 5-11. It had high hydrolytic activity against tributyrin, tripropionin, and trimyristin among various triglycerides. The gene encoding the lipase was cloned in Escherichia coli. Sequence analysis showed an open reading frame of 2136 bp, which encodes a preproenzyme of 711 amino acids. The preproenzyme is composed of a signal peptide (60 aa), a pro-peptide (259 aa), and a mature enzyme (392 aa). The mature enzyme has 49-67% amino acid sequence homology with other staphylococcal lipases.
Several neurodegenerative diseases including Huntington disease, Machado-Joseph disease and spinocerebellar ataxias type 1 are caused by expansion of a polyglutamine tract within their respective gene products. In order to assess the role of the tract, 293T cells were transfected with plasmids that contain various lengths of CAG repeat encoding polyglutamine without the repeat disorder proteins: (CAG)27, (CAG)40, (CAG)80, (CAG)130, and (CAG)180. Except for (CAG)27, and (CAG)40, 293T cells showed a common set of morphological alterations such as shrinkage, rounding and surface blebbing when the expanded stretch was expressed. In addition, nuclear staining experiments showed chromatin condensation in COS-7 cells transfected with the vectors containing expanded CAG repeats. These results indicate that expanded polyglutamine itself is able to induce cell death, suggesting existence of a common molecular mechanism in the etiology of neurodegenerative polyglutamine diseases.
Opsins are a class of retinal-binding, seven transmembrane helix proteins that function as light-responsive ion pumps or sensory receptors. Previously, genes encoding opsins had been identified in animals and the Archaea but not in fungi or other eukaryotic microorganisms. Here, we report the identification and mutational analysis of an opsin gene, nop-1, from the eukaryotic filamentous fungus Neurospora crassa. The nop-1 amino acid sequence predicts a protein that shares up to 81.8% amino acid identity with archaeal opsins in the 22 retinal binding pocket residues, including the conserved lysine residue that forms a Schiff base linkage with retinal. Evolutionary analysis revealed relatedness not only between NOP-1 and archaeal opsins but also between NOP-1 and several fungal opsin-related proteins that lack the Schiff base lysine residue. The results provide evidence for a eukaryotic opsin family homologous to the archaeal opsins, providing a plausible link between archaeal and visual opsins. Extensive analysis of Deltanop-1 strains did not reveal obvious defects in light-regulated processes under normal laboratory conditions. However, results from Northern analysis support light and conidiation-based regulation of nop-1 gene expression, and NOP-1 protein heterologously expressed in Pichia pastoris is labeled by using all-trans [3H]retinal, suggesting that NOP-1 functions as a rhodopsin in N. crassa photobiology.
Preferential binding of SeqA protein to hemimethylated oriC, the origin of Escherichia coli chromosomal replication, delays methylation by Dam methylase. Because the SeqA-oriC interaction appears to be essential in timing of chromosomal replication initiation, the biochemical functions of SeqA protein and Dam methylase at the 13-mer L, M, and R region containing 4 GATC sequences at the left end of oriC were examined. We found that SeqA protein preferentially bound hemimethylated 13-mers but not fully nor unmethylated 13-mers. Regardless of strand methylation, the binding of SeqA protein to the hemimethylated GATC sequence of 13-mer L was followed by additional binding to other hemimethylated GATC sequences of 13-mer M and R. On the other hand, Dam methylase did not discriminate binding of 13-mers in different methylation patterns and was not specific to GATC sequences. The binding specificity and higher affinity of SeqA protein over Dam methylase to the hemimethylated 13-mers along with the reported cellular abundance of this protein explains the dominant action of SeqA protein over Dam methylase to the newly replicated oriC for the sequestration of chromosomal replication. Furthermore, SeqA protein bound to hemimethylated 13-mers was not dissociated by Dam methylase, and most SeqA protein spontaneously dissociated 10 min after binding. Also, SeqA protein delayed the in vitro methylation of hemimethylated 13-mers by Dam methylase. These in vitro results suggest that the intrinsic binding instability of SeqA protein results in release of sequestrated hemimethylated oriC.
Sarcoidosis is a chronic, multisystemic disorder of unknown etiology. The incidence of central nervous system involvement is as high as 5%. Although steroids have been the cardinal treatment for sarcoidosis, many patients become symptomatically unresponsive to them. Other patients may suffer from glucose intolerance, cataracts, and obesity, which are adverse effects of high-dose steroids. Various reports in the literature suggest that some chemotherapeutic agents and/or radiation may be useful in these situations. We present three patients with neurosarcoidosis who were treated with radiation at a single institution. We also review previous reports on radiation-treated neurosarcoid patients. While the results vary, some patients clearly derive symptomatic benefits from low-dose radiation. Since the side effects of low-dose cranial irradiation are minimal, it may be prudent to use radiation therapy for patients who are refractory to steroids or who suffer adversely from high-dose steroids.
CD4+ lymphocytes exhibit variable permissiveness to the replication of HIV-1. A cohort of sexually-exposed-yet-uninfected individuals were previously shown to have CD4+ lymphocytes refractory for M-tropic viral replication. In particular, two individuals from this population whose CD4+ lymphocytes exhibited complete resistance to M-tropic viral replication were later shown to be homozygous for a 32bp (delta32) deletion in the gene encoding for CCR5. In screening diverse populations, HIV-1 infected individuals heterozygous for the delta32 allele were statistically favored in their disease course to harbor lower viral loads and exhibit slower rates of CD4+ cell loss when compared to control CCR5 wild-type individuals. Further comparative analysis between individuals in the exposed but uninfected cohort who demonstrated intermediate levels of in vitro viral replication and CD4+ lymphocytes isolated from uninfected delta32 heterozygous individuals indicate that reduced levels of in vitro M-tropic replication are a CCR5-related phenomenon: CD4+ lymphocytes from these individuals were more sensitive to the HIV-1 blocking effects of recombinant chemokines, displayed lower CCR5 cell surface expression levels and a proportionate increase in the production of RANTES when compared to CD4+ lymphocytes from control individuals. These results suggest that the CCR5 phenotype is important in determining the replicative capacity of M-tropic HIV-1 in vitro. The implications of these results with relation to HIV-1 transmission and disease progression are discussed.
BACKGROUND: Finasteride, a specific inhibitor of type II 5alpha-reductase, decreases serum and scalp dihydrotestosterone and has been shown to be effective in men with vertex male pattern hair loss. OBJECTIVE: This study evaluated the efficacy of finasteride 1 mg/day in men with frontal (anterior/mid) scalp hair thinning. METHODS: This was a 1-year, double-blind, placebo-controlled study followed by a 1-year open extension. Efficacy was assessed by hair counts (1 cm2 circular area), patient and investigator assessments, and global photographic review. RESULTS: There was a significant increase in hair count in the frontal scalp of finasteride-treated patients (P < .001), as well as significant improvements in patient, investigator, and global photographic assessments. Efficacy was maintained or improved throughout the second year of the study. Finasteride was generally well tolerated. CONCLUSION: In men with hair loss in the anterior/mid area of the scalp, finasteride 1 mg/day slowed hair loss and increased hair growth.
We report here that ultraviolet irradiation substantially reduced the mRNA and protein of the two major nuclear retinoid receptors, RAR-gamma and RXR-alpha, in human skin in vivo. Pre-treatment with retinoic acid mitigated this loss of nuclear retinoid receptors. Ultraviolet irradiation caused a near-total loss of retinoic acid induction of two RAR/RXR target genes, cellular retinoic acid binding protein-II and RA 4-hydroxylase, but did not affect 1,25-dihydroxyvitamin D3 induction of the vitamin D receptor/RXR-regulated gene vitamin D 24-hydroxylase. In effect, ultraviolet irradiation causes a functional vitamin A deficiency that may have deleterious effects on skin function, contributing to skin photo-aging and carcinogenesis.
Accumulating evidence has emphasized the importance of immunocompetent cells in determining the psoriatic phenotype. We have investigated the effect of 1alpha,25-dihydroxycholecalciferol, the naturally occurring active form of vitamin D3, cyclosporine A, and interleukin-10 on the phenotype of human psoriatic skin xenotransplants. First, psoriatic skin transplants were injected with either 1alpha,25-dihydroxy- cholecalciferol, cyclosporine A, or interleukin-10. Second, we determined the ability of autologous lymphocytes, activated in vitro using staphylococcal enterotoxin B and interleukin-2 and then exposed to either 1alpha, 25-dihydroxycholecalciferol or cyclosporine A, to induce psoriatic lesions if they were injected into the dermis of uninvolved skin grafts. We found that injections into transplanted psoriatic plaques of either 1alpha,25-dihydroxycholecalciferol or cyclosporine A, but not interleukin-10, resulted in a consistent reduction in the clinical and histologic score of psoriasis with remission towards uninvolved psoriatic skin. Injection of activated immunocytes into symptomless psoriatic skin grafts, changed the grafts towards plaque-type psoriasis with silvery scale, parakeratosis, elongated rete pegs, acanthosis, and dermal angiogenic reaction. In contrast, if activated immunocytes were exposed to 1alpha, 25-dihydroxycholecalciferol or cyclosporine A prior to injection, only minimal changes occurred. It was determined that neither staphylococcal enterotoxin B and interleukin-2 activation by itself, nor the drugs investigated, changed the CD4/CD8 ratio of activated (CD25 + ) cells. Our results are consistent with the hypothesis that psoriasis may be induced by activated T lymphocytes, and indicate that novel immunomodulatory drugs can serve to inhibit the pathogenetic ability of immunocytes in psoriasis.
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Engagement of the B7 family of molecules on antigen-presenting cells with their T cell-associated ligands, CD28 and CD152 (cytotoxic T lymphocyte-associated antigen-4 [CTLA-4]), provides a pivotal costimulatory signal in T-cell activation. We investigated the role of the CD28/CD152 pathway in psoriasis in a 26-week, phase I, open-label dose-escalation study. The importance of this pathway in the generation of humoral immune responses to T cell-dependent neoantigens, bacteriophage phiX174 and keyhole limpet hemocyanin, was also evaluated. Forty-three patients with stable psoriasis vulgaris received 4 infusions of the soluble chimeric protein CTLA4Ig (BMS-188667). Forty-six percent of all study patients achieved a 50% or greater sustained improvement in clinical disease activity, with progressively greater effects observed in the highest-dosing cohorts. Improvement in these patients was associated with quantitative reduction in epidermal hyperplasia, which correlated with quantitative reduction in skin-infiltrating T cells. No markedly increased rate of intralesional T-cell apoptosis was identified, suggesting that the decreased number of lesional T cells was probably likely attributable to an inhibition of T-cell proliferation, T-cell recruitment, and/or apoptosis of antigen-specific T cells at extralesional sites. Altered antibody responses to T cell-dependent neoantigens were observed, but immunologic tolerance to these antigens was not demonstrated. This study illustrates the importance of the CD28/CD152 pathway in the pathogenesis of psoriasis and suggests a potential therapeutic use for this novel immunomodulatory approach in an array of T cell-mediated diseases.
1,25-Dihydroxyvitamin D3 (D3) exerts its effects by binding to and activating nuclear vitamin D3 receptors (VDRs) that regulate transcription of target genes. We have investigated regulation of VDR levels in human skin in vivo and in cultured human keratinocytes. Quantitative ligand-binding analysis revealed that human skin expressed approximately 220 VDRs per cell, which bound D3 with high affinity [(dissociation constant (Kd) = 0.22 nM]. In human skin nuclear extracts, VDR exclusively bound to DNA containing vitamin D3 response elements as heterodimers with retinoid X receptors. Topical application of D3 to human skin elevated VDR protein levels 2-fold, as measured by both ligand-binding and DNA-binding assays. In contrast, the D3 analog calcipotriene had no effect on VDR levels. Topical D3 had no effect on VDR mRNA, indicating that D3 either stimulated synthesis and/or inhibited degradation of VDRs. To investigate this latter possibility, recombinant VDRs were incubated with skin lysates in the presence or absence of D3. The presence of D3 substantially protected VDRs against degradation by human skin lysates. VDR degradation was inhibited by proteasome inhibitors, but not lysosome or serine protease inhibitors. In cultured keratinocytes, D3 or proteasome inhibitors increased VDR protein without affecting VDR mRNA levels. In cells, VDR was ubiquitinated and this ubiquitination was inhibited by D3. Proteasome inhibitors in combination with D3 enhanced VDR-mediated gene expression, as measured by induction of vitamin D3 24-hydroxylase mRNA in cultured keratinocytes. Taken together, our findings indicate that low VDR levels are maintained, in part, through ubiquitin/proteasome-mediated degradation and that low VDR levels limit D3 signaling. D3 exerts dual positive influences on its nuclear receptor, simultaneously stimulating VDR transactivation activity and retarding VDR degradation.
The external elastic lamina (EEL) serves as a barrier for cells and macromolecules between the media and adventitia in the vascular wall. We evaluated the morphological changes and quantitative assessments of the EEL architecture in the coronary circulation of pigs fed with a high cholesterol diet. Confocal microscopy analysis of the EEL from hypercholesterolemic coronary arteries revealed an altered pattern characterized by fragmentation and disorganization of the EEL associated with an increase in the thickness. Computerized digital analysis of the images obtained by confocal scanning microscopy demonstrated that compared to normal coronary arteries, the EEL of hypercholesterolemic coronary arteries decreased in the percentage of their elastin content (30.80 +/- 1.64% vs. 47.85 +/- 1.82%, p = 0.001). The percentage of elastin content was negatively correlated with the vessel wall area (r = -0.82, p = 0.001). The immunoreactivity for matrix metalloproteinase-3 (MMP-3) increased in cholesterol-fed coronary arteries, predominantly in the neointima and adventitia. This study demonstrates that experimental hypercholesterolemia induced ultrastructural changes of the EEL in coronary circulation. The EEL may also be an atherosclerosis-prone area compared with the intima. The EEL may play an important role in the development of structural changes which characterizes the early phase of coronary atherosclerosis and vascular remodeling.
OBJECTIVE: In order to solve the difficult problem of one-stage repair of degloving injury of multiple fingers, the common pedicled ilio-inguinal-hypogastric subdermal vascular network skin flap was designed and the multi-lobes skin flap was performed subsequently. METHODS: From 1993 to 1996, there were 5 cases with degloving injuries of multiple fingers were treated by this flap. There were 2 males and 3 females and the age ranged from 7 to 19 years old. RESULTS: After operation, the pedicles of the flap was detached between 12 to 16 days and all of the flaps survived completely. Patients were followed up for 6-18 months. After repair, the contour and skin colour of the digits were excellent, and the motion of the interphalangeal joints and skin sensation were good. CONCLUSION: The conclusion was as follows: The newly designed skin flap was characterized by the advantages of duration of treatment being short, excellent contour and more rapid recovery of function. It could be used for one-stage repair of degloving injury of multiple fingers.
In order to investigate if the enhanced expression of Rb confers increased cellular resistance to adriamycin, we made Rb stable transfectants from colon carcinoma cells, SW620. Rb stable transfectants exhibited 5- to 10-fold more resistance to adriamycin than the control cells. To study the correlation between enhanced Rb expression and MDR1 expression, products of the Rb gene and the MDR1 gene in Rb stable transfectants were measured by Western blot analysis. These Rb transfectants showed increased MDR1 expression. Transient transfection of the MDR1 promoter-CAT reporter gene and the Rb gene demonstrated that Rb up-regulated MDR1 promoter activity in SW620 cells. Rb may, at least partly, contribute to a role in protecting cells from carcinogen exposure by up-regulating the MDR1 gene.