Techniques: species' finest blend--humanized mouse models in inflammatory skin disease research

Differences between humans and mice often hamper the transfer of promising results from the bench to the clinic. For ethical reasons, research that involves patients is limited, and so there is an urgent need for models that mimic the human situation as closely as possible. In recent years, there has been considerable progress in generating humanized mouse models, and their application to drug discovery has proved fruitful. So, how can mice be humanized, and how can humanized mice be employed in immunology research and drug discovery? In this article, we answer these questions, focusing on T-cell-mediated skin diseases as an example.     

Development of a forced choice photographic questionnaire for photic phenomena and its testing - repeatability, reliability and validity

AIM: To design, develop and test a system for analysis of photic phenomena. METHOD: Extensive background research, patient interviews and theoretical studies led to development of a set of photographic images resembling photic phenomena experienced by patients. These photographic images were processed and digitally altered to create scales of severity for each photic phenomenon in which patients indicated their severity of symptoms by choice of image. The system was tested for stability and validity. RESULTS: The system showed excellent repeatability and reliability. Face, content, criterion and construct validity were all found to be acceptable. CONCLUSION: The photographic images of photic phenomena analyser is an acceptable, validated measure for the assessment of photic phenomena, in both pseudophakic patients and those with cataract.     

Selectin and selectin ligand binding: a bittersweet attraction

Inhibition of leukocyte migration into target organs has long been an attractive, though challenging, basis for anti-inflammatory strategies. However, to date, the manipulation of leukocyte rolling along blood vessels has not yielded successful new therapies. An important study may now open new avenues in this exciting field of anti-inflammatory therapies by introducing a putative inhibitor of poly-N-acetyllactosamine biosynthesis that affects selectin ligand activity and shows efficacy in a rodent skin inflammation model.     

Expectant management of early pregnancies of unknown location: a prospective evaluation of methods to predict spontaneous resolution of pregnancy

Objective To assess prospectively the ability of two multiparameter diagnostic models and their individual components to predict the outcome of early pregnancies which could not be identified on transvaginal ultrasound scan.
Design Prospective observational study.
Setting Dedicated early pregnancy unit in an inner city teaching hospital.
Population Women with a positive urine pregnancy test and clinical suspicion of early pregnancy complications.
Methods A full medical history, clinical examination and transvaginal ultrasound scan were carried out at the initial visit. When the location of the pregnancy could not be ascertained by ultrasound, serum beta-human chorionic gonadotrophin ( β -hCG) and progesterone levels were measured. All women were managed expectantly until either a normal pregnancy was visualised on scan; the pregnancy resolved spontaneously or intervention was required due to a worsening of clinical symptoms or non-declining β -hCG levels.
Main outcome measures Spontaneous resolution of pregnancy (i.e. cessation of symptoms and decline in serum β -hCG level to < 20 iu/L) without need for any active intervention.
Results Of the 104 women recruited, 72 (69%) pregnancies resolved spontaneously. Both multiparameter diagnostic models identified resolving pregnancies with positive predictive values  ≥ 95%  . Their performances were not significantly better compared with individual progesterone levels which achieved a positive predictive value of 97% using a cutoff level of 20 nmol/L.
Conclusion Serum progesterone measurement alone is as accurate as more complex diagnostic models for the prediction of successful expectant management in pregnancies of unknown location.     

A novel, soluble homologue of the human IL-10 receptor with preferential expression in placenta

The cytokine receptor family type 2 (CRF2) comprises receptors for important immunomediators like interferons and interleukin-10 (IL-10). We identified a novel member of this family which represents the first exclusively soluble receptor in this group and was therefore designated as CRF2-soluble 1 (CRF2-s1). The CRF2-s1 gene covers about 28 kb and is located on chromosome 6 in close proximity to the CRF2 members interferon (IFN)-gamma receptor 1 and IL-20 receptor 1. It comprises seven exons and generates two different mRNA splice variants, CRF2-s1-long and CRF2-s1-short. CRF2-s1-long and CRF2-s1-short encode proteins of 263 and 231 amino acids, respectively. A comparison of predicted protein structures led to the postulation that each receptor variants binds a different ligand. Quantitative analysis of human mRNA expression revealed a very restricted pattern for both splice forms. CRF2-s1 turned out to be the first member of this receptor family which was expressed neither in resting nor in stimulated leucocyte populations. CRF2-s1-long was only expressed in placenta, whereas CRF2-s1-short was additionally expressed in human mammary gland and, at a lower level, in skin, spleen, thymus and stomach. The preferential expression of CRF2-s1 in placenta suggests a role for this receptor in establishing and maintaining successful pregnancy.     

Difficult cases in heart failure: reversible cardiomyopathy due to atrial fibrillation in a 46-year-old patient

The authors describe the challenging case of a 46-year-old patient who presented with a 2-week history of exertional dyspnea, paroxysmal nocturnal dyspnea, and orthopnea. He was found to have left ventricular failure and atrial fibrillation with a rapid ventricular rate. Initial work-up revealed dilated cardiomyopathy with marked left ventricular dysfunction, without any obvious cause. He received standard medical therapy for left ventricular dysfunction and his symptoms improved. Electrical cardioversion to sinus rhythm and maintenance resulted in complete recovery of left ventricular function within 6 months. (c)2001 CHF, Inc.