Ribosome display and affinity maturation: from antibodies to single V-domains and steps towards cancer therapeutics

Vascular endothelium is an important site for a wide array of immunological processes such as inflammation, atherosclerosis and allograft rejection. Culture methods of mouse vascular endothelium would provide an important in vitro correlate to immunological murine in vivo models. We describe a simple method to culture mouse vascular endothelium from thoracic aorta. Our cultured cells express typical phenotypic (CD105, CD31, CD106), morphological and ultrastructural (intercellular junctions, Weibel-Palade bodies) markers of vascular endothelium. They also possess functional receptors for uptake and processing of acetylated low-density lipoproteins. The mouse vascular endothelium within our system expresses high levels of MHC class I and MHC class II after activation with IFN-gamma. In addition, these cells express the accessory molecules CD80 and CD54, while they lack constitutive expression of CD86 and CD40, providing them the means to function as antigen presenting cells. Alloreactive CD4(+) and CD8(+) T lymphocytes demonstrate evidence of DNA synthesis after co-culture with activated vascular endothelium indicating their commitment to proliferation. In conclusion, we describe a simple culture system to isolate and grow mouse vascular endothelium, which provides a powerful tool to study biological interactions in vitro.     

Platelet monoamine oxidase activity and life stress as predictors of psychopathology and coping in a community sample

The present study, using a diathesis-stress model, attempted to confirm prior findings with platelet monoamine oxidase (MAO) activity and stress in a middle-aged, non-clinic population. One hundred and seventy-eight adult males from a statewide community club were tested for platelet MAO activity and stressful life events and were also given a variety of psychological measures of both psychopathology and psychosocial coping. The data were examined both for correlations across the total sample and for a comparison of high-risk groups (top and bottom 15% of MAO activity) with a middle MAO group. Low platelet MAO activity was related to a higher incidence of contact with mental health professionals, and more frequent use of alcohol and cigarette smoking. High MAO activity was related to higher levels of anxiety and somatization. High levels of stress were related to increased psychosocial problems reported for female and family members, higher scores on two schizophrenia-related MMPI scales (schizophrenia and paranoia subscales), but fewer idiosyncratic associations, elevated hypomanic, depression, and anxiety scores, increased alcohol use, and increased use of prescribed antianxiety and sedative medication. Neither MAO nor stress were related to current levels of psychosocial coping. Moreover, no interaction effects were uncovered for MAO activity and stress combined.     

A cell surface monoclonal antibody (H366) helps to discriminate human cytotoxic from suppressor T cells.

A study has been undertaken to differentiate T cytotoxic (Tc) and T suppressor (Ts) cell subsets using a monoclonal antibody termed H366 (mouse IgG2b) previously reported to phenotype natural killer and killer (NK/K) cells. Mononuclear cell suspensions from 14 normal subjects were depleted of H366+ cells by means of complement dependent cytotoxicity and the remaining cells were phenotyped with CD8 and CD4 monoclonal antibodies. The effects of depletion with H366 plus complement (C1) on the induction and activity of suppressor and cytotoxic T cells was also examined. The results indicate that H366 antibody recognizes in addition to NK/K cells, a population of Tc but not Ts or helper cells. Therefore, H366 antibody can be useful for obtaining Ts enriched lymphocyte subpopulations and this property may also be used for the enumeration of suppressor cells in the peripheral blood in disease states.     

Long-term metabolic effects of truncal vagotomy and gastrojejunostomy for chronic duodenal ulcer

In a review of 305 consecutive patients who had undergone truncal vagotomy and gastrojejunostomy for duodenal ulceration 5-15 (mean 10.5) years before, symptomatic and metabolic sequelae were related to a dietary survey in 109 patients. The incidence of post vagotomy symptoms was related to the incidence of weight loss and reduced dietary energy intake. The dietary survey did not show any trends in the incidence of weight loss since operation. Biochemical steatorrhoea occurred in 48% of 96 patients, but this was not related to dietary fat intake, or to weight loss unless diarrhoea was also present. Anaemia was noted in 13% of patients, but the incidence was not related to dietary survey, age, symptoms or post-vagotomy gastric acid output.     

A randomized controlled trial evaluating combination detection of HIV in Malawian sexually transmitted infections clinics

IntroductionHIV diagnosis is the necessary first step towards HIV care initiation, yet many persons living with HIV (PLWH) remain undiagnosed. Employing multiple HIV testing strategies in tandem could increase HIV detection and promote linkage to care. We aimed to assess an intervention to improve HIV detection within socio‐sexual networks of PLWH in two sexually transmitted infections (STI) clinics in Lilongwe, Malawi.MethodsWe conducted a randomized controlled trial to evaluate an intervention combining acute HIV infection (AHI) screening, contract partner notification and social contact referral versus the Malawian standard of care: serial rapid serological HIV tests and passive partner referral. Enrolment occurred between 2015 and 2019. HIV‐seropositive persons (two positive rapid tests) were randomized to the trial arms and HIV‐seronegative (one negative rapid test) and ‐serodiscordant (one positive test followed by a negative confirmatory test) persons were screened for AHI with HIV RNA testing. Those found to have AHI were offered enrolment into the intervention arm. Our primary outcome of interest was the number of new HIV diagnoses made per index participant within participants’ sexual and social networks. We also calculated total persons, sexual partners and PLWH (including those previously diagnosed) referred per index participant.ResultsA total of 1230 HIV‐seropositive persons were randomized to the control arm, and 561 to the intervention arm. Another 12,713 HIV‐seronegative or ‐serodiscordant persons underwent AHI screening, resulting in 136 AHI cases, of whom 94 enrolled into the intervention arm. The intervention increased the number of new HIV diagnoses made per index participant versus the control (ratio: 1.9; 95% confidence interval (CI): 1.2 to 3.1). The intervention also increased the numbers of persons (ratio: 2.5; 95% CI: 2.0 to 3.2), sexual partners (ratio: 1.7; 95% CI: 1.4 to 2.0) and PLWH (ratio: 2.3; 95% CI: 1.7 to 3.2) referred per index participant.ConclusionsCombining three distinct HIV testing and referral strategies increased the detection of previously undiagnosed HIV infections within the socio‐sexual networks of PLWH seeking STI care. Combination HIV detection strategies that leverage AHI screening and socio‐sexual contact networks offer a novel and efficacious approach to increasing HIV status awareness.     

Use of psychoactive substances in three medical specialties: anaesthesia,medicine and surgery

In order to determine the prevalence of psychoactive substance use in three specialty groupings, 1,624 questionnaires were sent to physicians in medicine, surgery and anaesthesia; all had trained at the same academic institution. A response rate of 57.8% was achieved. Comparison of prevalence of impairment rates showed no differences between Surgery (14.4%), Medicine (19.9%) and Anaesthesia (16.8%). Substance abuse was clearly associated with a family history of abuse; 32.1% of the abusers had a family history of such abuse compared with 11.7% of the non-abusers. Increased stress at various career stages did not appear to increase substance abuse; problem areas during medical life times were similar for each specialty. Substances most frequently used were marijuana (54.7%), amphetamines (32.9%); and benzodiazepines (25.1%). Seventy-three used psychoactive drugs which were non-prescribed. Drug counselling programmes were judged inadequate by most. Use of alcohol and drugs by faculty members was reported by a number of respondents.     

Integrated communications perspectives and the practice of total quality management

Communication is becoming increasingly identified as a significant factor influencing the ability of the NHS to achieve high-quality outcomes. Typically, organizations have tended to conceptualize communication as a process dealing with external relationships. Emphasizes the importance of both internal and external communications, and argues that the NHS now needs to integrate both these dimensions of the communication function. Proposes a strategic framework which suggests how this can be accomplished. Proposes and discusses a communications-centred model of the management process in the light of this approach. This model integrates perspectives which have hitherto dichotomized management as either a science or an art. It also locates communication at the heart of effective management. Finally, suggests the NHS is uniquely well placed to provide data on the impact and costs of total communication programmes.