A viral protease-mediated cleavage of the transmembrane glycoprotein of Mason-Pfizer monkey virus can be suppressed by mutations within the matrix protein.

The envelope glycoprotein precursor of retroviruses undergoes proteolytic cleavage in the Golgi complex to yield the mature surface and transmembrane (TM) glycoproteins of the virus. We report here that the TM glycoprotein of Mason-Pfizer monkey virus undergoes a second proteolytic processing event during a late maturation step that can follow virus release and Gag polyprotein cleavage. Cleavage results in the conversion of the cell-associated TM glycoprotein (gp22) to a virus-associated gp20. Processing continues after virus release and yields virions that contain predominantly gp20. A mutation within the active site of the Mason-Pfizer monkey virus aspartyl protease was shown to block both TM glycoprotein cleavage and the processing of the Gag polyprotein precursor. The role of the viral protease in cleavage of the TM glycoprotein localizes the cleavage site to the cytoplasmic domain of this protein. Surprisingly, point mutations within the matrix (MA) coding region of the gag gene can affect the extent to which gp22 is processed to gp20 and in one case [p10(MA)-A79V] results in greater than 90% inhibition of gp22 cleavage. The data provide genetic evidence of a specific interaction between the capsid proteins and the cytoplasmic domain of the TM glycoprotein of a retrovirus. This interaction is required for cytoplasmic domain cleavage to occur and may play a critical role in virus assembly and viral infectivity.     

Impact of single immunosuppressive drug withdrawal on lymphocyte immunoreactivity

Background

Chronic rejection is a major cause of graft loss in kidney transplant recipients. Nonadherence to drug therapy is a well-recognized cause of chronic rejection leading to long-term graft dysfunction and failure for transplant recipients. Immunosuppressive medications with short half-lives that require frequent dosing, such as tacrolimus, complicate transplant regimens and may increase noncompliance. Regimens could be simplified using drugs with long half-lives requiring once-daily administration, such as sirolimus. The impact of missing doses of single agents has not been studied extensively. Erratic compliance or temporary discontinuation of immunosuppressive drugs may have significant implications for chronic rejection.

Methods

Our study evaluated the impact of single drug withdrawal of commonly used immunosuppressive agents (sirolimus and tacrolimus) on lymphocyte responses. We analyzed lymphocyte proliferation, cytokine secretion, and adenosine triphosphate generation using a crossover study design with normal healthy patients. Lymphocyte proliferation was assessed using 5-bromo-2-deoxyuridine incorporation, and T cell function was analyzed by examining adenosine triphosphate generation.

Results

Our results indicate that sirolimus exerts prolonged suppression of lymphocyte proliferation and decreased interleukin 17A that lasts up to 48 h after drug withdrawal. In comparison, tacrolimus did not have a similar effect on lymphocyte proliferation or interleukin 17A secretion.

Conclusion

Future analysis of sirolimus in diverse transplantation populations merits investigation.     

The impact of early cytomegalovirus infection after kidney transplantation on long‐term graft and patient survival

This prospective observational cohort study is an extension of a previous study reporting effects of cytomegalovirus (CMV) on graft and patient survival in 471 patients who underwent kidney transplantation between 1994 and 1997. CMV pp65 antigen was measured every 7–14 d during the first three months after transplantation, given as number of CMV pp65‐positive cells per 10⁵ leukocytes. A positive test was defined as CMV infection. None of the patients received CMV prophylaxis or preemptive treatment. During a median of 13.7 (7.1–14.9) yr, the number of death‐censored graft losses was 118 (25%) and of patient deaths 224 (48%). CMV infection was an independent significant risk factor for mortality in multivariate analysis (HR = 1.453, 95% CI 1.033–2.045, p = 0.032), adjusting for patient and donor age, preemptive transplantation, HLA‐DR and ‐AB mismatches, living donor, acute rejection during the first three months, donor–recipient CMV IgG antibody status and diabetic nephropathy. In univariate analysis, CMV infection was significantly associated with death‐censored graft loss but the association was not significant in multivariate model. CMV infection early after kidney transplantation is a predictor of overall mortality but not of death‐censored graft loss after a median observation period of 13.7 yr.     

The necessity of a test reading after 1 week to detect late positive patch test reactions in patients with oral lichen lesions

Objectives

Establishing the clinical relevance of contact allergy to dental materials in patients with oral lichen lesions (OLL) may be difficult, and tests are often read only on day 3 or day 4; also, concentration of the tested allergens may vary. Several studies on dermatitis patients have shown that additional positive patch test reactions can be found after day 4. Therefore, the aim of the present study was to analyse the frequency of late positive reactions to potential allergens in patients with OLL.

Material and methods

Eighty-three of 96 consecutive patients with biopsy-verified OLL were patch-tested with a recently developed lichen series. The patches were removed after 48 h and reactions read 3 and 7 days after application.

Results

A total of 129 contact allergies were found, and 26 (20.2 %) of the allergic reactions in 23 patients were seen on day 7 only. The 25.2 % increase in positive test reactions with an additional reading on day 7 in addition to day 3 was statistically significant. Metals were the substances with the highest frequency of late positive reactions.

Conclusions

Patients with OLL cannot be considered properly investigated with regard to contact allergy, unless the testing has been performed with mandatory readings on day 3 (or day 4) and day 7.

Clinical relevance

Late patch test readings are crucial in order to elucidate the role of contact allergy to dental materials in the aetiology of OLL.     

RNA viruses in community-acquired childhood pneumonia in semi-urban Nepal; a cross-sectional study

Background  

Pneumonia is among the main causes of illness and death in children <5 years of age. There is a need to better describe the epidemiology of viral community-acquired pneumonia (CAP) in developing countries.     

Therapeutic electrical stimulation in cerebral palsy: a randomized, controlled, crossover trial

The aim of this study was to evaluate the effect of therapeutic electrical stimulation (TES) applied to antagonists of spastic leg muscles on gross motor function in children with spastic diplegic cerebral palsy. Twelve children between 5 and 12 years of age completed a 24-month crossover study in which six were randomly assigned to receive TES for the first 12 months and the remaining six for the last 12 months. Physiotherapy and a home training program were not altered. All were evaluated blindly in terms of tests of motor function and video recordings at the start and at 12 and 24 months. At the end of the study parents/carers gave a subjective assessment of the effect of TES. No significant effect of TES on motor or ambulatory function was found on the blinded evaluation, but parents of 11 of the 12 children stated that TES had a significant effect. We conclude that it is unlikely that TES has a significant effect on motor and ambulatory function in spastic diplegia.     

Personality and behaviour in eight-year-old,non-handicapped children with birth weight under 1500 g

Personality and behavioural characteristics of a population-based cohort of 29 very low-birth-weight (VLBW) infants were compared with those of 29 matched, term controls at eight years of age. The VLBW infants were born to families of lower socioeconomic status (p = 0.04) and had a lower mean IQ (93 versus 104, p = 0.008) and motor abilities (p = 0.028). Based on the questionnaire personality inventory for children, the VLBW children had more learning difficulties and school coping problems, and the VLBW boys had more conduct and emotional problems than the controls. Except for conduct problems, these differences persisted after controlling for socioeconomic status. Generally, there were significant relationships between behaviour, IQ and motor abilities. In conclusion, VLBW may be a risk factor for the development of school coping and behavioural problems independent of socioeconomic status but often coexist with impaired cognitive and neuromotor function.     

Phototoxicity of Dictamnus alba *

Phytophotodermatitis from Dictamnus alba was observed in three patients. Thin-layer chromatography and spectrophotometry disclosed the occurrence of 5-methoxypsoralen: md 8-methoxypsoralen in the plant extracts which was also demonstrated by their photo-toxic activity in vitro.