Diabetic autonomic neuropathy: evidence for apoptosis in situ in the rat

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75065/1/j.1365-2982.2004.00524.x.pd

Cholinesterase Inhibitors and Hospitalization for Bradycardia: A Population-Based Study

Laura Park-Wyllie and colleagues examined the health records of more than 1.4 million older adults and show that initiation of cholinesterase inhibitor therapy is associated with a more than doubling of the risk of hospitalization for bradycardia

TUNEL – an efficient prognosis predictor of salivary malignancies

Biological markers are necessary for predicting prognosis of salivary malignancies and better understanding the pathogenesis of salivary cancer. We analysed terminal deoxynucleotidyl transferase (TdT)-mediated biotinylated deoxyuridine-triphosphate (dUTP)-biotin nick-end labelling (TUNEL), p53 and Ki67 expression in 66 patients with malignant salivary tumours by immonohistochemistry, and correlated the data with survival, disease-free survival, tumour grade, stage, and local and distant metastasis. TUNEL efficiently predicted poor prognosis in salivary malignancies. The 5-year (5Y) survival probability dropped significantly with the level of TUNEL staining (from 83% in negatively stained tumours to 57 and 24% in TUNEL positively stained levels 1 and 2, respectively), (P=0.042). Extensive Ki67 staining (in addition to TUNEL) reduced the 5Y-survival rate even further and addition of positively stained p53 dropped the 5Y-survival rate to 0. The correlation rates between TUNEL and Ki67 was 58% (P=0.0001), and between TUNEL and p53 it was 50% (P=0.035). Concurrently, TUNEL correlated with metastasis, extracapsular spread, grade and stage. The correlation between TUNEL, p53 and Ki67 staining and survival probabilities, and the pathological grade, stage and metastasis spread of salivary malignancies makes this a highly effective tool in patient follow-up and prognosis

“Where, O Death, Is Thy Sting?” A Brief Review of Apoptosis Biology

Apoptosis was a term introduced in 1972 to distinguish a mode of cell death with characteristic morphology and apparently regulated, endogenously driven mechanisms. The effector processes responsible for apoptosis are now mostly well known, involving activation of caspases and Bcl2 family members in response to a wide variety of physiological and injury-induced signals. The factors that lead of the decision to activate apoptosis as opposed to adaptive responses to such signals (e.g. autophagy, cycle arrest, protein synthesis shutoff) are less well understood, but the intranuclear Promyelocytic Leukaemia Body (PML body) may create a local microenvironment in which the audit of DNA damage may occur, informed by the extent of the damage, the adequacy of its repair and other aspects of cell status

Small DNA Pieces in C. elegans Are Intermediates of DNA Fragmentation during Apoptosis

While studying small noncoding RNA in C. elegans, we discovered that protocols used for isolation of RNA are contaminated with small DNA pieces. After electrophoresis on a denaturing gel, the DNA fragments appear as a ladder of bands, ∼10 nucleotides apart, mimicking the pattern of nuclease digestion of DNA wrapped around a nucleosome. Here we show that the small DNA pieces are products of the DNA fragmentation that occurs during apoptosis, and correspondingly, are absent in mutant strains incapable of apoptosis. In contrast, the small DNA pieces are present in strains defective for the engulfment process of apoptosis, suggesting they are produced in the dying cell prior to engulfment. While the small DNA pieces are also present in a number of strains with mutations in predicted nucleases, they are undetectable in strains containing mutations in nuc-1, which encodes a DNase II endonuclease. We find that the small DNA pieces can be labeled with terminal deoxynucleotidyltransferase only after phosphatase treatment, as expected if they are products of DNase II cleavage, which generates a 3′ phosphate. Our studies reveal a previously unknown intermediate in the process of apoptotic DNA fragmentation and thus bring us closer to defining this important pathway

Inhibition of telomerase activity by HDV ribozyme in cancers

<p>Abstract</p> <p>Background</p> <p>Telomerase plays an important role in cell proliferation and carcinogenesis and is believed to be a good target for anti-cancer drugs. Elimination of template function of telomerase RNA may repress the telomerase activity.</p> <p>Methods</p> <p>A pseudo-knotted HDV ribozyme (g.RZ57) directed against the RNA component of human telomerase (hTR) was designed and synthesized. An in vitro transcription plasmid and a eukaryotic expression plasmid of ribozyme were constructed. The eukaryotic expression plasmid was induced into heptocellular carcinoma 7402 cells, colon cancer HCT116 cells and L02 hepatocytes respectively. Then we determine the cleavage activity of ribozyme against human telomerase RNA component (hTR) both in vitro and in vivo, and detect telomerase activity continuously.</p> <p>Results</p> <p>HDV ribozyme showed a specific cleavage activity against the telomerase RNA in vitro. The maximum cleavage ratio reached about 70.4%. Transfection of HDV ribozyme into 7402 cells and colon cancer cells HCT116 led to growth arrest and the spontaneous apoptosis of cells, and the telomerase activity dropped to 10% of that before.</p> <p>Conclussion</p> <p>HDV ribozyme (g.RZ57) is an effective strategy for gene therapy.</p

Search for CP violation in D+→ϕπ+ and D+s→K0Sπ+ decays

A search for CP violation in D + → ϕπ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fb−1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (−0.04 ± 0.14 ± 0.14)% for candidates with K − K + mass within 20 MeV/c 2 of the ϕ meson mass. A search for a CP -violating asymmetry that varies across the ϕ mass region of the D + → K − K + π + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+s→K0Sπ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%

Long-term outcome and prognosis of dissociative disorder with onset in childhood or adolescence

<p>Abstract</p> <p>Background</p> <p>In the majority of cases short-term treatment outcome of juvenile dissociative disorder is rather favourable. In contrast, the long-term course seems to be less positive, but meaningful results are still fragmentary. The aim of this follow-up study is to bridge this gap to some extent describing the long-term outcome of juvenile dissociative disorder in a clinical sample. To our knowledge there is no comparable other long-term follow-up study which is based on a case definition according to actual classification systems using standardized interviews for individual assessment of the patients at the time of follow-up.</p> <p>Methods</p> <p>The total study group was made up of all patients treated for dissociative disorder at our department for child and adolescent psychiatry between 1983 and 1992 (<it>N </it>= 62). Two of these former patients committed suicide during the follow-up period (3%). We got information on the clinical course of 27 former patients (44%). 17 out of these 27 former patients were female (63%). The mean age of onset of dissociative disorder was11.7 years and the mean follow-up time was 12.4 years. Most of the patients were reassessed personally (n = 23) at a mean age of 24.8 years using structured interviews covering dissociative disorders, other Axis I disorders and personality disorders (Heidelberg Dissociation Inventory HDI; Expert System for Diagnosing Mental Disorders, DIA-X; Structured Clinical Interview for DSM-IV, SCID-II). Social adjustment was assessed by a semi-structured interview and by patient self report (Social Adjustment Scale – Self Report, SAS-SR). Psychosocial outcome variables were additionally assessed in 36 healthy controls (67% female, mean age = 22.9 years).</p> <p>Results</p> <p>At the time of follow-up investigation 82.6% of the patients met the criteria for some form of psychiatric disorder, while 26.1% were still suffering from dissociative disorder. A total of 56.5% presented with an Axis I disorder (especially anxiety, dissociative and somatoform disorders). Personality disorders were seen in 47.8% (especially borderline, obsessive-compulsive and negativistic personality disorders). More dissociative symptoms and inpatient treatment in childhood or adolescence were significantly related to a lower level of psychosocial adjustment in adulthood.</p> <p>Conclusion</p> <p>Treatment strategies have to consider that in a significant portion of young patients initial recovery may not be stable over time. Limitations of the study refer to the small sample size and the low rate of former patients taking part in the follow-up investigation.</p

Expression of Bcl-2 and Bax in Mouse Renal Tubules during Kidney Development

Bcl-2 and Bax play an important role in apoptosis regulation, as well as in cell adhesion and migration during kidney morphogenesis, which is structurally and functionally related to mitochondria. In order to elucidate the role of Bcl-2 and Bax during kidney development, it is essential to establish the exact location of their expression in the kidney. The present study localized their expression during kidney development. Kidneys from embryonic (E) 16-, 17-, 18-day-old mouse fetuses, and postnatal (P) 1-, 3-, 5-, 7-, 14-, 21-day-old pups were embedded in Epon. Semi-thin serial sections from two E17 kidneys underwent computer assisted 3D tubule tracing. The tracing was combined with a newly developed immunohistochemical technique, which enables immunohistochemistry on glutaraldehyde fixated plastic embedded sections. Thereby, the microstructure could be described in detail, and the immunochemistry can be performed using exactly the same sections. The study showed that Bcl-2 and Bax were strongly expressed in mature proximal convoluted tubules at all time points, less strongly expressed in proximal straight tubules, and only weakly in immature proximal tubules and distal tubules. No expression was detected in ureteric bud and other earlier developing structures, such as comma bodies, S shaped bodies, glomeruli, etc. Tubules expressing Bcl-2 only were occasionally observed. The present study showed that, during kidney development, Bcl-2 and Bax are expressed differently in the proximal and distal tubules, although these two tubule segments are almost equally equipped with mitochondria. The functional significance of the different expression of Bcl-2 and Bax in proximal and distal tubules is unknown. However, the findings of the present study suggest that the mitochondrial function differs between mature proximal tubules and in the rest of the tubules. The function of Bcl-2 and Bax during tubulogenesis still needs to be investigated