ABSTRACT
Objective: To investigate the association between plasma selenium exposure and the risk of impaired glucose regulation (IGR). Methods: A case-control study was conducted to select IGR patients who were admitted to the outpatient clinic of the Department of Endocrinology to perform oral glucose tolerance test(OGTT) at the Tongji Hospital affiliated to the Tongji Medical College from September 2004 to 2016 as a case group. Participants with normal glucose tolerance recruited from an unselected group of population undergoing routine health examinations in the same hospital were selected as a control group. The control group was matched according to the age (±5 years old) and sex of the case group. The inclusion criteria for subjects recruited were as follows: age ≥30 years, body mass index (BMI) <40â¯kg/m(2), no history of a diagnosis of IGR or type 2 diabetes, and no history of receiving pharmacological treatment for hyperlipidemia or hypertension. Patients with any clinically systemic disease such as neurological or endocrine disease, acute illness, chronic inflammatory disease or infectious disease were excluded from the study. A total of 1 957 subjects, 897 in the case group and 1 060 in the control group, were included. Questionnaires were used to collect information of all subjects, and peripheral venous blood was collected after fasting and OGTT, respectively. Plasma selenium, fasting blood glucose, blood lipid (total cholesterol, triglycerides, high density lipoprotein cholesterol, and low density lipoprotein cholesterol) and 2 h OGTT plasma glucose concentration were detected, respectively. The subjects were divided into low, medium and high concentration groups according to the tertiles of plasma selenium concentration in the control group. The multivariate unconditional logistic regression analysis was performed to analyze the association between plasma selenium exposure and IGR. Results: The age (mean±SD) of the case and control group was (53.71±11.38) and (53.95±12.17) years old. The plasma selenium concentration [M (P(25), P(75))] in the case group was 92.81(77.07, 107.05) µg/L, which was significantly higher than the control group [88.73 (77.13, 100.88) µg/L] (P<0.05). The results of multivariate unconditional logistic regression analysis showed that after adjusting for age, sex, BMI, family history of diabetes and hypertension, the risk of IGR was higher in the high-concentration group and the low-concentration group compared with the middle-concentration group, the values of OR (95%CI) were 1.22 (95%CI: 0.94-1.59) and 1.81 (95%CI: 1.42-2.30), respectively. Conclusion: The study suggested a U-shaped association between plasma selenium and IGR.
Subject(s)
Diabetes Mellitus, Type 2 , Glucose Intolerance , Selenium , Adult , Aged , Blood Glucose/metabolism , Body Mass Index , Case-Control Studies , Child, Preschool , China/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Glucose , Humans , Middle Aged , Selenium/bloodABSTRACT
Cervical necrotising fasciitis is a progressive deep infection of the neck associated with high mortality, and skillful management of the airway is critical for operations under general anaesthesia. Tracheostomy under local anaesthesia has been considered the gold standard of airway management in patients with deep neck infections, but it may be difficult or impossible in advanced cases. We report here our experience over 6 years (January 2008 and December 2013) during which a total of 15 patients was diagnosed with cervical necrotising fasciitis. Of 6 patients, admitted between January 2008 and March 2010, 5 had routine tracheostomy under local anaesthesia, 1 had direct laryngoscopy intubation, and 9 who were admitted between Spring 2010 and December 2013 were treated with nasotracheal intubation. Postoperatively all patients were given moderate sedation and analgesia. Nasotracheal intubation was continued until the infection had been controlled. During intubation patency of the endotracheal tube was maintained by humidification with a continuous pump of 0.45% sodium chloride and suction. All 15 patients (10 men and 5 women, mean age 62 years, range 36-93) required an emergency drainage procedure under general anaesthesia. Fourteen of the 15 had evidence of compromise of the airway, but emergency intervention was not required. Since Spring 2010, 9 consecutive patients had required nasotracheal intubation, including 7 video laryngoscopies and 2 fibreoptic bronchoscopies. No other interventions were required. Patients were intubated postoperatively from 3 to 14 days, and there were no problems with the airway. Advanced techniques for control of the airway have a high rate of success in patients with necrotising fasciitis and could be an appropriate alternative to a traditional airway. Postoperative sedation and analgesia should be considered as routine management of pain and anxiety.
Subject(s)
Airway Management/methods , Fasciitis, Necrotizing/therapy , Neck/pathology , Adult , Aged , Aged, 80 and over , Analgesia/methods , Anesthesia, General/methods , Anesthesia, Local/methods , Bronchoscopy/methods , Conscious Sedation/methods , Female , Humans , Humidity , Intubation, Intratracheal/instrumentation , Intubation, Intratracheal/methods , Laryngoscopy/methods , Male , Middle Aged , Optical Fibers , Pain Management/methods , Retrospective Studies , Sodium Chloride/therapeutic use , Suction/methods , Tracheostomy/methods , Video RecordingABSTRACT
OBJECTIVES: To determine the prevalence and clinical associations of Mycoplasma genitalium in urethral, rectal and pharyngeal specimens collected from men who have sex with men (MSM) attending male-only saunas. METHODS: A cross-sectional study of 521 MSM attending six male-only saunas in Melbourne was conducted between October 2001 and September 2002. Stored urine and rectal and pharyngeal swabs were tested for M genitalium by real-time polymerase chain reaction. The prevalence of M genitalium and clinical associations were determined. RESULTS: A high prevalence (12.9%; 95% CI 10.2% to 15.9%) of sexually transmitted infections (STIs) was found in MSM. M genitalium (2.1%; 95% CI 1.1% to 3.6%) was less common than Chlamydia trachomatis (8.1%; 95% CI 5.9% to 10.6%, p<0.001), and Neisseria gonorrhoeae (4.8%; 95% CI 3.2% to 6.9%, p = 0.02). M genitalium was most likely to be detected as an asymptomatic rectal (1.6%; 95% CI 0.8% to 3.0%) or urethral infection (0.6%; 95% CI 0.2% to 1.6%, p = 0.12), but was absent from the pharynx. In comparison, C trachomatis was more common in the rectum (6.2%; 95% CI 4.3% to 8.6%) than urethra (1.8%; 95% CI 0.9% to 3.2%, p = 0.004), and was uncommon in the pharynx (0.6%; 95% CI 0.1% to 1.6%). Urethral infection with N gonorrhoeae (0.2%; 95% CI 0.01% to 1.0%) was rare, but it was as common in the pharynx (2.5%; 95% CI 1.4% to 4.2%) as the rectum (2.2%; 95% CI 1.2% to 3.8%). No significant demographic or behavioural associations with M genitalium were identified. CONCLUSION: M genitalium was less common than C trachomatis and N gonorrhoeae in MSM attending male-only saunas and was most often detected as an asymptomatic rectal or a urethral infection but was absent from the pharynx. To inform STI screening strategies in MSM, more data are needed to understand how common M genitalium infection is in urethral and non-urethral sites in MSM, and how it contributes to clinical symptoms.
Subject(s)
Homosexuality, Male , Mycoplasma Infections/microbiology , Mycoplasma genitalium/isolation & purification , Sexually Transmitted Diseases/microbiology , Steam Bath , Adolescent , Adult , Aged , Aged, 80 and over , Chlamydia trachomatis/isolation & purification , Cross-Sectional Studies , Humans , Male , Middle Aged , Mycoplasma Infections/epidemiology , Neisseria gonorrhoeae/isolation & purification , Pharynx/microbiology , Polymerase Chain Reaction , Prevalence , Recreation , Rectum/microbiology , Risk Factors , Sexually Transmitted Diseases/epidemiology , Urethra/microbiology , Victoria/epidemiology , Young AdultABSTRACT
Niemann-Pick disease type C (NP-C) is a lipid storage disorder characterized by the accumulation of unesterified cholesterol and glycolipids in the lysosomal/late endosomal system of certain cells in the central nervous system (CNS) and visceral organs. Clinical symptoms include progressive neurological deterioration and visceral organomegaly. Miglustat, a small iminosugar molecule approved for the treatment of Gaucher disease, reversibly inhibits glucosylceramide synthase, which catalyses the first committed step in glycosphingolipid synthesis. The physicochemical properties of miglustat allow it to cross the blood-brain barrier and suggest possible benefits in lysosomal storage diseases affecting the CNS. Here, we present findings in two children with NP-C, aged 14 years (patient 1) and 9 years (patient 2), treated with miglustat for 1 year. Before treatment, patient 1 presented with severe difficulties in swallowing and walking, and patient 2 with problems mostly affecting communication and social interaction. Videofluoroscopic studies in patient 1 demonstrated a substantial improvement in swallowing by month 6 of treatment, and ambulation index measurements indicated improved walking. Mini Mental-State Examination (MMSE) assessments in patient 2 showed cognitive improvement by month 6, which was sustained up to month 12. Liver/spleen volume and plasma chitotriosidase activities were stabilized in both cases. There was no weight loss during treatment. Patient 1 experienced severe but self-limiting paresthesia, which was not associated with peripheral neuropathy. We conclude that miglustat can provide therapeutic benefits in CNS symptoms and allows stabilization of systemic disease in childhood-onset NP-C. Further follow-up is crucial to determine the long-term maintenance of these effects.
Subject(s)
1-Deoxynojirimycin/analogs & derivatives , Enzyme Inhibitors/therapeutic use , Glucosyltransferases/antagonists & inhibitors , Niemann-Pick Disease, Type C/drug therapy , 1-Deoxynojirimycin/pharmacology , 1-Deoxynojirimycin/therapeutic use , Adolescent , Child , Cognition/drug effects , Deglutition/drug effects , Enzyme Inhibitors/pharmacology , Glucosyltransferases/metabolism , Humans , Interpersonal Relations , Niemann-Pick Disease, Type C/enzymology , Niemann-Pick Disease, Type C/physiopathology , Niemann-Pick Disease, Type C/psychology , Recovery of Function/drug effects , Severity of Illness Index , Time Factors , Treatment Outcome , Verbal Behavior/drug effects , WalkingABSTRACT
PURPOSE: A previous study has shown that the pulsatile ocular blood flow (POBF) in eyes with asymmetric age-related macular degeneration (AMD) differs. Whereas eyes with drusen have higher POBF than contralateral eyes with disciform scarring, the POBF of eyes with drusen is lower relative to contralateral eyes with choroidal neovascularization (CNV). This study was designed to assess whether the POBF of eyes with CNV changes after transpupillary thermotherapy (TTT), using the contralateral eyes with drusen or scarring without TTT as controls. METHODS: In total, 26 patients with CNV in one eye and drusen or scarring in the other were enrolled in this prospective case series. Eyes with CNV were treated with TTT. POBF was measured monthly in both eyes of each subject. RESULTS: Before TTT, the POBF of eyes with CNV was 1179+/-317 microl/min. After TTT, the POBF of CNV eyes had decreased at 1 month (1015+/-273 microl/min, P=0.002) and 2 months (945+/-398 microl/min, P=0.011) of follow-up, but had rebounded at 3 months (P=0.441) and 6 months (P=0.084). CONCLUSIONS: These findings suggest that TTT decreases the pulsatile choroidal blood flow in eyes with CNV in patients with asymmetric AMD and the effects persist for 2 months. POBF may be used as a modality to monitor the therapeutic effects of CNV in asymmetric exudative AMD.
Subject(s)
Choroidal Neovascularization/physiopathology , Eye/blood supply , Hyperthermia, Induced , Macular Degeneration/therapy , Aged , Blood Pressure , Female , Humans , Macular Degeneration/physiopathology , Male , Manometry , Prospective Studies , Pulsatile Flow , Retinal Drusen/physiopathologyABSTRACT
A six-year-old boy was diagnosed with beta-thalassaemia major during infancy. Since then, he required monthly blood transfusion and irregular iron chelation therapy. He had hepatosplenomegaly and elevated liver enzymes; the serum ferritin was up to 3800 ng/mL. An echocardiogram showed left-ventricular enlargement. His one-antigen-mismatched mother was chosen as a bone marrow donor. He was pretreated with intensive red blood cell transfusion and hydroxyurea for 6 weeks prior to conditioning. The conditioning included total body irradiation (300 cGy), busulfan (14 mg/kg), cyclophosphamide (160 mg/kg) and anti-thymocyte globulin (rabbit; 90 mg/kg). Marrow cell dose was 5.4 x 108/kg. Graft versus host disease (GVHD) prophylaxis included cyclosporine A (CSA) and methylprednisolone. Neutrophil engraftment occurred on day 23. Grade II acute GVHD occurred on day 45. The patient developed complications including septicaemia, haemorrhagic cystitis, intracranial haemorrhage and heart failure. He subsequently recovered from the complications without sequelae. The patient remained transfusion-independent at a follow-up examination after 18 months. This case suggested that a mismatched family member may be considered as a bone marrow donor for beta-thalassaemia major. In places where conventional treatment is not feasible, for example, in China, this approach may be an alternative option. A more intensive immunosuppressive regimen and a higher marrow cell dose may be important for successful engraftment. High-dose anti-thymocyte globulin may also prevent severe GVHD.
Subject(s)
Bone Marrow Purging/methods , Bone Marrow Transplantation/methods , beta-Thalassemia/therapy , Child , Follow-Up Studies , Graft Survival , Graft vs Host Disease/prevention & control , HLA Antigens/analysis , Histocompatibility Testing , Humans , Male , Parents , Risk Assessment , Severity of Illness Index , Tissue Donors , Transplantation Immunology , Transplantation, Homologous , Treatment Outcome , beta-Thalassemia/diagnosisABSTRACT
Phototherapy is effectively employed for the treatment of neonatal hyperbilirubinemia, but it may influence the physiological hemodynamics of the infants, such as skin blood flow, insensible water loss and the redistribution of cardiac output. This is a retrospective chart review study involved totally 42 very low birth weight prematures(birth body weight less than 1500 gm, VLBW) who received conventional or fiberoptic phototherapy. Infants with congenital malformation, severe cardiorespiratory instability and the requirement of diuretics, inotropics or blood transfusion were excluded. The body weight loss, daily intake/output and bilirubin level during the initial four days of phototherapy were analyzed. The results showed the efficacy of both methods was the same, while the fiberoptic therapy group had significantly more urine output(p < 0.05), the body weight loss was not statistically significant. It is possible that the fiberoptic therapy group had less insensible water loss and less attenuation of the decrease of renal blood flow, this resulted in more urine output.
Subject(s)
Infant, Very Low Birth Weight , Jaundice, Neonatal/therapy , Phototherapy/methods , Chi-Square Distribution , Female , Humans , Infant, Newborn , Male , Retrospective StudiesABSTRACT
A series of vanilloid-type beta-adrenoceptor blockers derived from antioxidant traditional Chinese herbal medicines were synthesized and tested for their antioxidant and adrenoceptor antagonistic activities. They all possessed significant beta-adrenoceptor blocking activities under in vitro experiments and radioligand binding assays. In addition, some compounds were further examined in in vivo tests and produced antagonist effects matching that of propranolol and labetalol by measurements of antagonism toward (-)isoproterenol-induced tachycardia and (-)phenylephrine-induced pressor responses in anesthetized rats. Furthermore, all of the compounds had antioxidant effects inherited from their original structures. In conclusion, compound 11 had the most potent beta-adrenoceptors blocking activity, 12 and 13 possessed high cardioselectivity, whereas 14, 15 and 16 possessed additional alpha-adrenoceptor blocking activity and 15 is the most effective antioxidant of all. The antioxidant activity may be due to their alpha and beta unsaturated side chain at position 1 and ortho-substituted methoxy moiety on 4-phenoxyethylamine.
Subject(s)
Adrenergic beta-Antagonists/chemical synthesis , Adrenergic beta-Antagonists/pharmacology , Antioxidants/chemical synthesis , Antioxidants/pharmacology , Adrenergic beta-Antagonists/metabolism , Animals , Antioxidants/metabolism , Brain/drug effects , Brain/metabolism , Guinea Pigs , In Vitro Techniques , Lipid Peroxidation , Magnetic Resonance Spectroscopy , Radioligand Assay , Rats , Rats, WistarABSTRACT
OBJECTIVE: To isolate and determine the strain of anamorph of Cordyceps sinensis collected from Naqu Tibet. METHOD: Isolating the strains of anamorph of Cordyceps sinensis collected from Baqing Shuoxian, Biru Counties by means of the ascope, tissue, ossified larva and body liquid. RESULT: Same strain of anamorph of Cordyceps sinensis was obtained with 4 different methods. CONCLUSION: The strain of Hirsutella sinensis is the anamorph of C. sinensis from Naqu Tibet.
Subject(s)
Fungi/isolation & purification , Lepidoptera/microbiology , Animals , Cordyceps/isolation & purification , Lepidoptera/anatomy & histology , TibetABSTRACT
OBJECTIVE: To Clarify the cause of the disease of Cordyceps sinensis host insect Paecilomyces muscardine. METHOD: Separately observing eggs, larvals, pupals, adults and their circumstances causing diseases in every stage. Adopting separately Hemolymph, bodies of dead insects and conidiospores; separating and culturing them, them observing and identifying the inoculum. Inoculating healthy larvals from the purely separated and cultured plants of inoculum. RESULT AND CONCLUSION: The original inoculum of the disease is Paecilongces frinoues, which may often be found in the period of larvals and seldom found in the period of pupals but never in that of adults and eggs. The main symptom of larval is dullness and weakness. But the typical Symptom is a layer of a kind of white power of conidiospore on the surface of the dead body which comes into being later stage.
Subject(s)
Lepidoptera/microbiology , Mycoses/microbiology , Paecilomyces/isolation & purification , Animals , Cordyceps , Materia MedicaABSTRACT
OBJECTIVE: To understand the morphological and anatomical characteristics of Dendrobium nobile so as to provide scientific basis for its domestication and cultivation. METHOD: The root's morphological development and interior structure were investigated. RESULT AND CONCLUSION: Dendrobium has peculiar structure which determines that this plant requires a growing environment with high water and air ventilation properties.
Subject(s)
Dendrobium/anatomy & histology , Plants, Medicinal/anatomy & histology , Plant Roots/anatomy & histologyABSTRACT
The Jem-1 (JEM-1, HGMW-approved symbol BLZF1) gene mapping to human chromosome 1q24 codes for a ubiquitously expressed 3-kb mRNA, translated in a 45-kDa nuclear protein. Recent studies have shown a deficient expression of this gene in acute promyelocytic leukemia (APL). However, treatment with retinoids was able to upregulate JEM-1 mRNA in maturing NB4 leukemia cells. Here, we report the characterization of the structural organization of JEM-1. By hybridization screening of a human genomic library derived from blood mononuclear cells, five overlapping genomic DNA clones were isolated. These clones extend over 34 kb of the human genome and comprise the complete JEM-1 gene and a 4-kb 5'flanking region. Determination of the exon-intron structure of Jem-1 revealed seven exons whose junctions with introns exhibited typical splice sequences. A shorter transcript (Jem-1s, 1.3 kb) generated by exon 3 extension and polyadenylation was identified. Its translation generated a 23-kDa protein that exhibited a cytoplasmic localization. 5'RACE-PCR identified a major transcription start site (TSS) located at 403 nt upstream of the ATG. Computer analysis of the 1. 8-kb 5'flanking region showed that it lacks a TATA box, Inr motifs or DPE motifs, but it contains a typical CCAAT box located 95 bp upstream of the TSS. Sequencing also revealed potential cis-acting elements for multiple transcription regulators including Sp1, GATA, C/EBP, AP-1, and Pu1. No retinoic acid receptor elements or retinoic X receptor elements were detected. This 1.8-kb DNA sequence showed a strong constitutive promoter activity determined by a luciferase-reporter gene assay in transiently transfected HeLa cells. Retinoids further increased luciferase expression 2.7-fold. We demonstrated that the 1-kb distal sequence contains yet unidentified elements reducing constitutive transcription. Thus, the maximal constitutive promoter activity was assigned to a -432 + 101 region overlapping the TSS. These data support the idea of a constitutive expression of JEM-1, but a negative regulation in APL released by retinoids.
Subject(s)
Chromosomes, Human, Pair 1 , Nuclear Proteins/genetics , Transcription Factors/genetics , 5' Untranslated Regions/analysis , Animals , Base Sequence , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors , Binding Sites , COS Cells , Chromosome Mapping , Cloning, Molecular , DNA, Complementary , Electronic Data Processing , Exons , Gene Expression , HeLa Cells , Humans , Introns , Molecular Sequence Data , Poly A , Promoter Regions, Genetic/physiology , RNA, Messenger/analysis , Transcription, Genetic , TransfectionABSTRACT
A new halimane diterpene, 3beta,5beta, 16alpha-trihydroxyhalima-13(14)-en-15,16-olide (1), and a new oxoprotoberberine alkaloid, (-)-8-oxopolyalthiaine (2), along with 20 known compounds, were isolated from a methanolic extract of Polyalthia longifolia var. pendula. The structures of compounds 1 and 2 were established by spectroscopic analysis. Several of these compounds were evaluated for cytotoxicity toward a small panel of human cell lines.
Subject(s)
Alkaloids/isolation & purification , Antineoplastic Agents, Phytogenic/isolation & purification , Berberine Alkaloids , Diterpenes/isolation & purification , Plants, Medicinal/chemistry , Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes/pharmacology , Drug Screening Assays, Antitumor , Humans , Magnetic Resonance Spectroscopy , Plant Extracts/chemistry , Plant Extracts/pharmacology , Spectrophotometry, Ultraviolet , Tumor Cells, CulturedABSTRACT
To elucidate the molecular mechanism of all-trans-retinoic acid (ATRA)-induced differentiation of acute promyelocytic leukemia (APL) cells, the gene expression patterns in the APL cell line NB(4) before and after ATRA treatment were analyzed using complementary DNA array, suppression-subtractive hybridization, and differential-display-polymerase chain reaction. A total of 169 genes, including 8 novel ones, were modulated by ATRA. The ATRA-induced gene expression profiles were in high accord with the differentiation and proliferation status of the NB(4) cells. The time courses of their modulation were interesting. Among the 100 up-regulated genes, the induction of expression occurred most frequently 12-48 hours after ATRA treatment, while 59 of 69 down-regulated genes found their expression suppressed within 8 hours. The transcriptional regulation of 8 induced and 24 repressed genes was not blocked by cycloheximide, which suggests that these genes may be direct targets of the ATRA signaling pathway. A balanced functional network seemed to emerge, and it formed the foundation of decreased cellular proliferation, maintenance of cell viability, increased protein modulation, and promotion of granulocytic maturation. Several cytosolic signaling pathways, including JAKs/STAT and MAPK, may also be implicated in the symphony of differentiation. (Blood. 2000;96:1496-1504)
Subject(s)
Antineoplastic Agents/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Leukemia, Promyelocytic, Acute/genetics , Leukemia, Promyelocytic, Acute/pathology , Tretinoin/pharmacology , Antineoplastic Agents/therapeutic use , Cell Differentiation/drug effects , Cell Differentiation/genetics , Humans , Leukemia, Promyelocytic, Acute/drug therapy , Signal Transduction/drug effects , Signal Transduction/genetics , Tretinoin/therapeutic use , Tumor Cells, CulturedABSTRACT
OBJECTIVE: To establish a gas chromatography fuzzy clustering analytical method for classifying of origin fungi of the Chinese traditional medicine, Hongqu. METHODS: The volatile and nonvolatile components of 7 ordinary species of Monascus including M. aurantiacus Lee, etc. were analyzed by capillary gas chromatog raphy using FID: Inlet temperature 280 degrees C, detector temperature 280 degrees C, temperature program 130 degrees C, 5 min-->10 degrees C.min-1-->200 degrees C, 10 min. RESULTS: In the peak number and contents of volatile and nonvolatile components of Monascus exist obviously differences through which Monascus can be distinguished easily by the main fingerprint peaks within 20 minutes. CONCLUSION: The capillary gas chromatography fuzzy clustering analytical method is useful to the identification of Monascus fungi.
Subject(s)
Monascus/classification , Chromatography, Gas , Cluster Analysis , Medicine, Chinese Traditional , Monascus/chemistryABSTRACT
To clone zinc finger genes expressed in hematopoietic system, we designed primers based on conserved Cys(2)/His(2) zinc finger sequences to amplify corresponding domains from mRNA of normal bone marrow and leukemia cell line NB4. DNA fragments of novel zinc finger genes were chosen and used as probe pool to screen cDNA libraries or subject to rapid amplification of cDNA ends in order to obtain full-length cDNA. Six cDNAs including whole open reading frame of zinc finger proteins, named as ZNF191, ZNF253 (BMZF-1), ZNF255 (BMZF-2), ZNF256 (BMZF-3), ZNF257 (BMZF-4), and ZNF254 (BMZF-5) were obtained. All six belong to the Krüppel-like zinc finger gene family, and typical transcriptional regulatory motifs exist in the N-terminal moiety, such as the SCAN box in ZNF191, and the KRAB domains in ZNF253, ZNF254, ZNF256, and ZNF257. A previously undefined sequence nominated as Krüppel-related novel box, which may represent a new transregulatory motif, was revealed at the N terminus of ZNF255. The transregulatory function of non-zinc finger regions of ZNF191, ZNF253, and ZNF255 were addressed in yeast and mammalian cells. The results indicated that ZNF255 might be a conditional transactivator, whereas ZNF253 and ZNF191 displayed a suppressive effect on the transcription in yeast and/or mammalian systems.
Subject(s)
Hematopoietic Stem Cells/metabolism , Zinc Fingers/genetics , Amino Acid Sequence , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Cells, Cultured , Cloning, Molecular , DNA, Complementary , Evolution, Molecular , Fetal Blood , Hematopoietic Stem Cells/cytology , Humans , Leukemia, Promyelocytic, Acute , Molecular Sequence Data , Open Reading Frames , Organ Specificity , Phylogeny , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sequence Alignment , Sequence Homology, Amino Acid , Tumor Cells, CulturedABSTRACT
Hypoxic pulmonary vasoconstriction underlies the development of high-altitude pulmonary edema. Anecdotal observations suggest a beneficial effect of garlic in preventing high-altitude symptoms. To determine whether garlic influences pulmonary vasoconstriction, we assessed the effect of garlic on pulmonary pressures in rats subjected to alveolar hypoxia and on vasoconstriction in isolated pulmonary arterial rings. Garlic gavage (100 mg/kg body wt) for 5 days resulted in complete inhibition of acute hypoxic pulmonary vasoconstriction compared with the control group. No difference in mean arterial pressure or heart rate response to hypoxia was seen between the groups. Garlic solution resulted in a significant dose-dependent vasorelaxation in both endothelium-intact and mechanically endothelium-disrupted pulmonary arterial rings. The administration of NG-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor) inhibited the vasodilatory effect of garlic by 80%. These studies document that garlic blocks hypoxic pulmonary hypertension in vivo and demonstrate a combination of endothelium-dependent and -independent mechanisms for the effect in pulmonary arterial rings.
Subject(s)
Garlic/therapeutic use , Hypertension, Pulmonary/prevention & control , Hypoxia , Muscle, Smooth, Vascular/physiology , Phytotherapy , Plant Extracts/pharmacology , Plants, Medicinal , Pulmonary Artery/physiology , Acetylcholine/pharmacology , Animals , Blood Pressure , Endothelium, Vascular/physiology , Hypertension, Pulmonary/physiopathology , In Vitro Techniques , Male , Muscle Contraction/drug effects , Muscle Contraction/physiology , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/physiopathology , NG-Nitroarginine Methyl Ester/pharmacology , Phenylephrine/pharmacology , Pulmonary Alveoli/physiology , Pulmonary Alveoli/physiopathology , Pulmonary Artery/drug effects , Pulmonary Artery/physiopathology , Rats , Rats, Sprague-Dawley , VasoconstrictionABSTRACT
Vanidilol, [4'-(2-hydroxy-3-(tert-butylamino)propoxy)-3'-methoxyphenyl] -benzaldehyde, newly synthesized from vanillin, is a vanilloid-type beta-adrenoceptor blocker. The beta-adrenoceptor-blocking properties of vanidilol were studied both in vivo and in vitro. Intravenous injection of vanidilol (1.0, 3.0, 5.0 mg/kg) in anesthetized Wistar rats produced a decrease in blood pressure and a dose-dependent bradycardia response. Vanidilol inhibited the tachycardia effects induced by (-)isoproterenol, but had no blocking effect on the arterial pressor responses induced by phenylephrine. In isolated guinea-pig tissues, vanidilol attenuated the (-)isoproterenol-induced positive chronotropic and inotropic effects of the atria and trachea relaxation responses in a concentration-dependent manner. The parallel shift to the right of the concentration-response curve of (-)isoproterenol suggested that the agent was a beta-adrenoceptor competitive antagonist. The apparent pA2 values for vanidilol on the right atria, left atria and trachea were 7.67 +/- 0.03, 7.89 +/- 1.02 and 7.66 +/- 0.15, respectively, denoting that vanidilol was a nonselective beta-blocker. The intrinsic sympathomimetic activity of vanidilol and propranolol was determined on isolated atria and trachea from reserpinized guinea pigs. Propranolol caused significantly negative inotropic and chronotropic effects at 10(-6) mol/l or above, whereas vanidilol possessed less cardiodepressant activities than propranolol. In reserpinized tracheal strips, vanidilol produced dose-dependent relaxant responses, but propranolol was ineffective. Preincubating the preparations with ICI 118,551 (0.1-10 nmol/l), a beta 2-adrenoceptor antagonist, significantly shifted the concentration-relaxation curves of vanidilol to a region of higher concentrations. In isolated guinea-pig thoracic aorta, vanidilol (0.1-10 mumol/l) inhibited the phenylephrine (10(-5) mol/l)-induced tonic contraction in vascular smooth muscle which was related to the block of calcium influx. In 20% saline-perfused rabbits, vanidilol showed a marked delay in intraocular pressure recovery, demonstrating an ocular hypotensive action. Binding characteristics of vanidilol and propranolol were evaluated in [3H]dihydroalprenolol binding to porcine ventricular membranes. Vanidilol was less potent than propranolol in competing for the beta-adrenoceptor-binding sites. On the other hand, vanidilol had a high hydrophilicity in comparison with propranolol. In conclusion, vanidilol exhibited nonselective beta-adrenoceptor blocking, vasorelaxant and ocular hypotensive activities, but was devoid of alpha-adrenoceptor blocking and beta 1-agonist activity. Partial beta 2-adrenoceptor agonist activity and inhibitory activity on calcium influx may share in the vasorelaxant activity.
Subject(s)
Adrenergic beta-2 Receptor Agonists , Adrenergic beta-Agonists/pharmacology , Adrenergic beta-Antagonists/pharmacology , Antihypertensive Agents/pharmacology , Vasodilator Agents/pharmacology , Animals , Benzaldehydes/chemical synthesis , Benzaldehydes/therapeutic use , Blood Pressure/drug effects , Drug Evaluation, Preclinical , Female , Guinea Pigs , Heart Rate/drug effects , In Vitro Techniques , Intraocular Pressure/drug effects , Male , Ocular Hypotension/drug therapy , Rabbits , Radioligand Assay , Rats , Rats, Wistar , Trachea/drug effectsABSTRACT
Retinoid-induced proliferation causing hyperleukocytosis is a severe complication of retinoid therapy in t(15;17) acute promyelocytic leukaemia. The molecular basis of this phenomenon is unknown. It is possible that the transiently enhanced cell proliferation results from RA-induction of growth regulatory genes. Using Differential Display of cDNAs from NB4 cells we have identified Jem, a novel gene transcript which is upregulated by retinoids during the early proliferative response in maturating cells but not in resistant cells. A 2.7 kb cDNA was cloned and sequenced. The open reading frame contains a 400 amino acid sequence corresponding to a novel 45 kDa basic protein (pI 8.9). The JEM DNA sequence is detected by FISH on human chromosome 1 at q24. The Jem peptide sequence shows a 'leucine-zipper' dimerisation motif with limited homology to Fos/Jun and ATF/CREB proteins and several putative phosphorylation sites. An atypical basic region may correspond to an unknown DNA-binding domain. The C-terminal end of Jem spans a long stretch featuring a PEST motif. After transfection into COS cells, the Jem protein shows a ponctuated nuclear localisation. We hypothesise that this novel nuclear factor may act as a transcription factor, or a coregulator, involved in either cell growth control and/or maturation.