ABSTRACT
The spindle assembly checkpoint (SAC) is a 'wait-anaphase' mechanism that has evolved in eukaryotic cells in response to the stochastic nature of chromosome-spindle attachments. In the recent past, different aspects of the SAC regulation have been described. However, the role of microRNAs in the SAC is vaguely understood. We report here that Mad1, a core SAC protein, is repressed by human miR-125b. Mad1 serves as an adaptor protein for Mad2 - which functions to inhibit anaphase entry till the chromosomal defects in metaphase are corrected. We show that exogenous expression of miR-125b, through downregulation of Mad1, delays cells at metaphase. As a result of this delay, cells proceed towards apoptotic death, which follows from elevated chromosomal abnormalities upon ectopic expression of miR-125b. Moreover, expressions of Mad1 and miR-125b are inversely correlated in a variety of cancer cell lines, as well as in primary head and neck tumour tissues. We conclude that increased expression of miR-125b inhibits cell proliferation by suppressing Mad1 and activating the SAC transiently. We hypothesize an optimum Mad1 level and thus, a properly scheduled SAC is maintained partly by miR-125b.
Subject(s)
Apoptosis , Cell Cycle Proteins/metabolism , MicroRNAs/metabolism , Mitosis , Nuclear Proteins/metabolism , 3' Untranslated Regions , Anaphase , Base Sequence , Calcium-Binding Proteins/metabolism , Cell Cycle Proteins/antagonists & inhibitors , Cell Cycle Proteins/genetics , Cell Line, Tumor , Cell Proliferation , Chromosome Aberrations , Down-Regulation , HCT116 Cells , Hep G2 Cells , Humans , M Phase Cell Cycle Checkpoints , Mad2 Proteins , MicroRNAs/genetics , Nuclear Proteins/antagonists & inhibitors , Nuclear Proteins/genetics , Repressor Proteins/metabolismABSTRACT
In-situ capped nanocrystalline gamma-Fe2O3, Co3O4, and Cu2O were prepared in 1,4-butanediol in aerobic conditions. X-ray diffraction (XRD) patterns show that the synthesised samples are nanocrystalline cubic oxides with crystallite sizes 9.5 nm, 13.4 nm, and 11 nm, respectively. Raman spectroscopy shows peaks at 350 cm(-1), 500 cm(-1), and 700 cm(-1), indicating that the iron oxide is gamma-Fe2O3; Mössbauer spectroscopy shows the presence of two Fe3(3+) sites. Transmission electron microscopy images show that the particle sizes of gamma-Fe2O3 and Co3O4 samples are 8.9 nm and 7 nm, respectively. The absence of agglomeration indicates that the synthesised nanoparticles are capped. FT-IR spectra show the presence of an organic moiety in the sample which acts as a capping agent. Thermogravimetry shows that the capping is stable up to 873 K in gamma-Fe2O3, and up to 400 K in Co3O4. The samples are soluble in water to form stable hydrosols. During synthesis of gamma-Fe2O3 a 6-line ferrihydrite is formed as an intermediate, which is stable in solution up to 473 K, and transforms to gamma-Fe2O3 at 483 K, by rapid dissolution-reprecipitation. In the syntheses of Co3O4 and Cu2O, no intermediates are formed.
Subject(s)
Nanotubes/chemistry , Oxides/chemistry , Polymers/chemistry , Cobalt/chemistry , Copper/chemistry , Crystallization , Ferric Compounds/chemistry , Iron , Materials Testing , Microscopy, Electron, Transmission , Nanostructures , Nanotechnology , Spectroscopy, Fourier Transform Infrared , Spectroscopy, Mossbauer , Spectrum Analysis, Raman , Temperature , Thermogravimetry , X-Ray DiffractionABSTRACT
One hundred patients with congestive cardiac failure (52 males and 48 females) with age ranging from 16 to 56 yrs (mean age 42 +/- 6) were studied to determine the relative prevalence of systolic and diastolic failures, their clinical profiles and common aetiologies. Age matched 25 control subjects were also studied to established a normal range of echocardiographic values for LV diastolic function. Thirty eight patients (38%) were found to have pure diastolic heart failure and another 5 (5%) and 57 (57%) were detected to have mixed and systolic failures respectively. An attempt to correlate the clinical assessment of diastolic failure with echo doppler study showed the sensitivity and specificity of the clinical criteria for diagnosis of diastolic heart failure to be 100% and 91.94% respectively. Of the 38 cases of diastolic failure detected 39.5% had hypertension, 31.6% ischaemic heart disease and 13.16% hypertrophic cardiomyopathy.
Subject(s)
Heart Failure/physiopathology , Adolescent , Adult , Diastole , Echocardiography, Doppler , Female , Humans , Male , Middle AgedABSTRACT
We compared the effects of Hydralazine and Isosorbide dinitrate (ISDN) with those of an angiotensin-converting-enzyme inhibitor, captopril on mortality in patients with chronic congestive heart failure (NYHA class III and IV). Patients receiving conventional treatment with digoxin and diuretics were randomly assigned to receive either placebo (n = 51), hydralazine-ISDN. (n = 50) or captopril (n = 52) in a double blind trial. At the end of 6 months there were 14 deaths in the placebo group (27.4%) as compared with 11 deaths in the hydralazine-ISDN group (22%)--a mortality reduction of 20% (P > 0.05) and 10 deaths in the captopril group (19.2%)--a mortality reduction of 30% (p > 0.05). At the end of one year, mortality was 50%, 42% and 30% in the placebo, hydralazine-ISDN and captopril groups respectively with a mortality reduction of 16% in the hydralazine-ISDN group (p > 0.05) and 40% in the captopril group (p < 0.05) compared to the placebo group. The mortality reduction was mainly due to reduction in deaths attributed to progressive heart failure. The data suggests that the addition of captopril to conventional treatment significantly reduces mortality in patients with severe congestive heart failure. Hydralazine-isorobide dinitrate also reduced mortality but statistically this was not significant.
Subject(s)
Captopril/therapeutic use , Heart Failure/drug therapy , Hydralazine/therapeutic use , Isosorbide Dinitrate/therapeutic use , Vasodilator Agents/therapeutic use , Adult , Aged , Chi-Square Distribution , Chronic Disease , Double-Blind Method , Drug Therapy, Combination , Female , Heart Failure/mortality , Humans , Male , Middle Aged , Vasodilation/drug effectsSubject(s)
Hypertension/therapy , Adolescent , Adult , Antihypertensive Agents/therapeutic use , Blood Pressure , Child , Female , Humans , Hypertension/diagnosis , Hypertension/physiopathology , Male , Middle Aged , Risk Factors , Time FactorsABSTRACT
With the aim of reducing myocardial infarction size, isosorbide dinitrate (ISDN) was tried in 27 patients of acute myocardial infarction (AMI). There was 11% reduction of infarction size, in the ISDN treated group, in comparison to that of non treated group, though the result was not statistically significant. But, many of the in-hospital complications were significantly less in the treated group. After a critical analysis of the result it was concluded that a statistically insignificant result, as regard reduction of infarction size in AMI, cannot always exclude the utility of a drug therapy in AMI.
Subject(s)
Isosorbide Dinitrate/therapeutic use , Myocardial Infarction/drug therapy , Creatine Kinase/analysis , Female , Humans , Isoenzymes , Male , Middle Aged , Myocardial Infarction/enzymologySubject(s)
Bundle-Branch Block/diagnosis , Electrocardiography , Sick Sinus Syndrome/diagnosis , Aged , Chronic Disease , Female , Humans , Male , Middle AgedSubject(s)
Myocardial Contraction , Myxedema/diagnosis , Systole , Adult , Female , Heart Ventricles/physiopathology , Humans , Male , Middle Aged , Myxedema/drug therapy , Thyrotropin/blood , Thyroxine/bloodSubject(s)
Heart Block/etiology , Surgical Procedures, Operative/adverse effects , Adult , Aged , Bundle-Branch Block/complications , Female , Humans , Male , Middle Aged , RiskSubject(s)
Early Ambulation , Length of Stay , Myocardial Infarction/rehabilitation , Female , Humans , Male , Middle Aged , Patient Discharge , Prospective StudiesSubject(s)
Cardiac Pacing, Artificial , Heart Block/therapy , Adult , Aged , Female , Heart Block/mortality , Humans , Long-Term Care , Male , Middle Aged , Pacemaker, ArtificialABSTRACT
Breakage of a pacer lead due to the pacemaker-twiddler's syndrome (PTS) occurred in 4 of 62 survivors following epicardial-intramural pacer lead implantation with the pulse generator placed in each case in a subcostal left upper quadrant subcutaneous pocket. The abdominal pulse generator pocket appears to invite spontaneously occurring PTS, more so in a pregnant woman. The important predisposing factor to the development of PTS is an excessively spacious pulse generator pocket containing a pool of fluid. Addition of a few simple modifications to the technique of cardiac pacing would prevent the complication; these include implantation of the pulse generator in a plane deeper to the pectoral muscles, suspending the pulse generator from the clavicle and application of vacuum-suction drainage to the generator pocket in the initial phase of wound healing. In the presence of an optimally fitting pulse generator pocket, PTS should be rare with subclavicular subpectoral pulse generator implantation without active patient participation. The syndrome may not be as rare a cause of pacer lead malfunction as may appear from the relative paucity of reports in the literature.