Induction of DR\IA antigens in human liver allografts: An immunocytochemical and clinicopathologic analysis of twenty failed grafts

Twenty failed human liver allograft specimens obtained at the time of retransplantation procedures were studied using a panel of monoclonal antibodies (T11, T4, T8, NK, B1, OKM1, OKM5, Ia, DR). A clinicopathologic analysis was used to distinguish between graft failures secondary to rejection (n=10) and those due, at least in part, to other causes (n=10). T lymphocytes constituted the major infiltrating cellular population in the liver in rejection cases, but significant numbers of B cells and monocytes/macrophages were present also. Following transplantation, but not before, the bile duct epithelium, as well as portal and central vein and hepatic artery endothelium expressed DR/Ia antigens. These structures are preferential targets of the rejection reaction. The selective destruction of bile ducts in livers undergoing rejection was manifested in these patients by striking elevations of serum gamma glutamyl transpeptidase (GGTP) activity, a marker of biliary epithelial damage. The induced expression of DR/Ia antigens on structures targeted for immune destruction may be an important event in the pathogenesis of liver allograft rejection. © 1985 by The Williams and Wilkins Co

Capturing Hiproofs in HOL Light

Hierarchical proof trees (hiproofs for short) add structure to ordinary proof trees, by allowing portions of trees to be hierarchically nested. The additional structure can be used to abstract away from details, or to label particular portions to explain their purpose. In this paper we present two complementary methods for capturing hiproofs in HOL Light, along with a tool to produce web-based visualisations. The first method uses tactic recording, by modifying tactics to record their arguments and construct a hierarchical tree; this allows a tactic proof script to be modified. The second method uses proof recording, which extends the HOL Light kernel to record hierachical proof trees alongside theorems. This method is less invasive, but requires care to manage the size of the recorded objects. We have implemented both methods, resulting in two systems: Tactician and HipCam

Impaired glucose tolerance or newly diagnosed diabetes mellitus diagnosed during admission adversely affects prognosis after myocardial infarction: An observational study

Objective To investigate the prognostic effect of newly diagnosed diabetes mellitus (NDM) and impaired glucose tolerance (IGT) post myocardial infarction (MI). Research Design and Methods Retrospective cohort study of 768 patients without preexisting diabetes mellitus post-MI at one centre in Yorkshire between November 2005 and October 2008. Patients were categorised as normal glucose tolerance (NGT n = 337), IGT (n = 279) and NDM (n = 152) on predischarge oral glucose tolerance test (OGTT). Primary end-point was the first occurrence of major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal MI, severe heart failure (HF) or non-haemorrhagic stroke. Secondary end-points were all cause mortality and individual components of MACE. Results Prevalence of NGT, impaired fasting glucose (IFG), IGT and NDM changed from 90%, 6%, 0% and 4% on fasting plasma glucose (FPG) to 43%, 1%, 36% and 20% respectively after OGTT. 102 deaths from all causes (79 as first events of which 46 were cardiovascular), 95 non fatal MI, 18 HF and 9 non haemorrhagic strokes occurred during 47.2 ± 9.4 months follow up. Event free survival was lower in IGT and NDM groups. IGT (HR 1.54, 95% CI: 1.06–2.24, p = 0.024) and NDM (HR 2.15, 95% CI: 1.42–3.24, p = 0.003) independently predicted MACE free survival. IGT and NDM also independently predicted incidence of MACE. NDM but not IGT increased the risk of secondary end-points. Conclusion Presence of IGT and NDM in patients presenting post-MI, identified using OGTT, is associated with increased incidence of MACE and is associated with adverse outcomes despite adequate secondary prevention

Analyses of Sustained Vowels in Down Syndrome (DS): A Case Study Using Spectrograms and Perturbation Data to Investigate Voice Quality in Four Adults With DS

OBJECTIVES: Automatic acoustic measures of voice quality in people with Down syndrome (DS) do not reliably reflect perceived voice qualities. This study used acoustic data and visual spectral data to investigate the relationship between perceived voice qualities and acoustic measures. STUDY DESIGN: Participants were four young adults (two males, two females; mean age 23.8 years) with DS and severe learning disabilities, at least one of whom had a hearing impairment. METHODS: Participants imitated sustained /i/, /u/, and /a/ vowels at predetermined target pitches within their vocal range. Medial portions of vowels were analyzed, using Praat, for fundamental frequency, harmonics-to-noise ratio, jitter, and shimmer. Spectrograms were used to identify the presence and the duration of subharmonics at onset and offset, and mid-vowel. The presence of diplophonia was assessed by auditory evaluation. RESULTS: Perturbation data were highest for /a/ vowels and lowest for /u/ vowels. Intermittent productions of subharmonics were evident in spectrograms, some of which coincided with perceived diplophonia. The incidence, location, duration, and intensity of subharmonics differed between the four participants. CONCLUSIONS: Although the acoustic data do not clearly indicate atypical phonation, diplophonia and subharmonics reflect nonmodal phonation. The findings suggest that these may contribute to different perceived voice qualities in the study group and that these qualities may result from intermittent involvement of supraglottal structures. Further research is required to confirm the findings in the wider DS population, and to assess the relationships between voice quality, vowel type, and physiological measures

Inhibition of apoptosis in human tumour cells by the tumour-associated serpin, SCC antigen-1

The squamous cell carcinoma antigen (SCC Ag) is a tumour-associated protein and a member of theserineproteaseinhibitor (serpin) family. The SCC Ag has been used as a serologic tumour marker for SCC progression, and its elevated serum levels are a risk factor for disease relapse. However, the biologic significance of this intracytoplasmic protein in cancer cells remains unknown. In this report, we demonstrated that apoptosis induced by 7-ethyl-10-hydroxycamptothecin, tumour necrosis factor-α (TNF-α) or interleukin (IL)-2-activated natural killer (NK) cells was significantly inhibited in tumour cells transduced with the SCC Ag-1 cDNA, as compared to control cells in vitro. Also, inhibition of the SCC Ag-1 expression in tumour cells by transfection of antisense SCC Ag-1 cDNA was accompanied by significantly increased sensitivity of these cells to apoptosis induced by etoposide or TNF-α. The mechanism of protection of tumour cells from apoptosis involved inhibition of caspase-3 activity and/or upstream proteases. In vivo, tumour cells overexpressing the SCC Ag-1 formed significantly larger tumours in nude mice than the SCC Ag-1-negative controls. Thus, overexpression of the SCC Ag-1, a member of the serpin family, in human cancer cells contributed to their survival by mediating protection from drug-, cytokine- or effector cell-induced apoptosis. © 2000 Cancer Research Campaig