Spectroscopically Determined Collagen Pyr/deH-DHLNL Cross-Link Ratio and Crystallinity Indices Differ Markedly in Recombinant Congenic Mice with Divergent Calculated Bone Tissue Strength

Whole bone strength can be partitioned into structural and material components. In three-point bending tests of 6-month-old female humeri from the HcB/Dem recombinant congenic series, strains HcB/8 and HcB/23 differed markedly in calculated failure stress but not ash percentage. Fourier transform infrared spectroscopic imaging was used to determine whether differences in the ratio of pyridinoline (pyr; nonreducible) to dehydrodihydroxynorleucine (de-DHLNL; reducible) collagen cross-links (XLR), mineral crystallinity, or spatial ordering could account for the strains' differing biomechanical performance. HcB/8 had significantly higher XLR and significantly higher crystallinity than HcB/23. XLR and crystallinity were highly and similarly correlated in both strains. There were no significant differences between the strains' one-dimensional spatial correlation functions, suggesting no difference in short-range order between them. The strong correlation between XLR and crystallinity reflects the interdependence of the protein and mineral elements of bone. The data illustrate the importance of material properties in addition to mineral quantity to bone tissue strength.     

The history of mast cell and basophil research – some lessons learnt from the last century

This year (2013) marks the 50th anniversary of death of Otto Carl Willy Prausnitz (1876–1963) and Heinz Küstner (1897–1963). The two physicians, when working at the Hygiene Institute at the University of Breslau, Germany (Prausnitz was the Head of the Institute), described in 1921 what is still called today the Prausnitz–Küstner or PK reaction showing that allergy could be transferred from the allergic person by transferring serum to a healthy person. Their discovery ended the belief that an anaphylactic/allergic reaction was caused by poisons, but to the contrary showed that the presence of the hypersensitivity factor could be transferred to other people. We know now that this factor is immunoglobulin E (IgE), sensitizing mast cells and basophils to respond to an allergic stimulus. We take this occasion to retrace some of the important discoveries and lessons learnt from the last century relating to the function of these two cell types as effectors of the IgE system and the mediators they produce.     

Plasmapheresis in the treatment of an acute pancreatitis due to protease inhibitor‐induced hypertriglyceridemia

The use of protease inhibitors such as ritonavir to treat HIV‐infected individuals has been associated with lipodystrophy, combined hyperlipidemias, and hypertriglyceridemia‐induced pancreatitis. We report here on the treatment by plasmapheresis of a HIV‐patient who presented with a rapid onset of severe ritonavir‐induced hypertriglyceridemia complicated with an acute pancreatitis. A 35‐year‐old HIV‐1 positive male following 3 weeks of ritonavir treatment presented with nausea, abdominal pain, a distended abdomen, and the following laboratory values: amylase (238 U/L), lipase (864 U/L), total cholesterol (27.1 mmol/L), and triglycerides (62.9 mmol/L). Following two plasmaphereses, the levels of total cholesterol, triglycerides, lipase, and amylase declined drastically and the patient was discharged home after 4 days with lipid and pancreatic enzyme levels within the reference range. To our knowledge, this is the first case of pancreatitis due to a PI‐induced hyperlipidemia in a HIV‐patient treated with plasmapheresis in an acute setting. J. Clin. Apheresis. 16:157–159, 2000. © 2001 Wiley‐Liss, Inc.     

Intra-operative quality assessment of coronary artery bypass grafts.

Early coronary artery bypass graft (CABG) failure is a troubling complication that may result in a wide range of problems, including refractory angina, myocardial infarction, low cardiac output, arrhythmia, and fatal heart failure. Early graft failures are related to poor quality and size of the distal native vascular bed, coagulation abnormalities, or technical problems involving the graft conduits and anastomoses. Unfortunately, graft failure is difficult to detect during surgery by visual assessment, palpation, or conventional monitoring. We evaluated the accuracy and utility of a transit-time, ultrasonic flow measurement system for measurement of CABGs. There were no differences between transit-time measurements and volumetric-time collected samples in an in vitro circuit over a range of flows from 10 to 100ml/min (Bland and Altman Plot, 1.96 SD). Two hundred and ninety-eight CABGs were examined in 125 patients. Graft flow rate was proportional to the target vessel diameter. Nine technical errors were detected and corrected. Flow waveform morphology provided valuable information related to the quality of the anastamosis, which led to the immediate correction of technical problems at the time of surgery.     

The role of keratinocyte growth factor in melanogenesis: a possible mechanism for the initiation of solar lentigines

Please cite this paper as: The role of keratinocyte growth factor in melanogenesis: a possible mechanism for the initiation of solar lentigines. Experimental Dermatology 2010; 19 : 865–872. Abstract: Solar lentigines (SLs) are hyperpigmentary lesions presented on sun‐exposed areas of the skin and associated with ageing. The molecular mechanism of SL initiation is not completely understood. Ultraviolet B (UVB) stimulates keratinocytes to produce interlukin‐1 alpha (IL‐1α), which then induces keratinocyte growth factor (KGF) secretion; therefore, we examined their possible roles in the induction of SLs. We found that KGF increases pigment production in both pigmented epidermal equivalents and human skin explants. In addition, UVB exposure increases KGF expression, and KGF treatment induces tyrosinase (TYR) expression in primary melanocytes. The KGF‐induced pigmentary changes were confirmed using pigmented Yucatan swine, and human skins grafted onto immuno‐deficient mice. In both model systems, the topical treatment with KGF, alone or in combination with IL‐1α, resulted in the in vivo formation of hyperpigmentary lesions with increased pigment deposition and elongated rete ridges, which resemble the histological features of human SLs. Preliminary immunohistochemical analysis of human skins showed a moderate increase in KGF, and a strong induction in KGF receptor (KGFR) in SL lesions. In summary, KGF increases pigment production and deposition in vitro and in vivo. Moreover, we show for the first time the in vivo generation of hyperpigmentary lesions with histological resemblance to human SLs and indicate the involvement of KGF/KGFR in the molecular pathology of human SLs.     

Component‐resolved diagnostics to direct in venom immunotherapy: Important steps towards precision medicine

Stings of Hymenoptera can induce IgE‐mediated systemic and even fatal allergic reactions. Venom‐specific immunotherapy (VIT) is the only disease‐modifying and curative treatment of venom allergy. However, choosing the correct venom for VIT represents a necessary prerequisite for efficient protection against further anaphylactic sting reactions after VIT. In the past, therapeutic decisions based on the measurement of specific IgE (sIgE) levels to whole venom extracts were not always straightforward, especially when the patient was not able to identify the culprit insect. In the last years, the increasing knowledge about the molecular structure and relevance of important venom allergens and their availability as recombinant allergens, devoid of cross‐reactive carbohydrate determinants, resulted in the development of an advanced component‐resolved diagnostics (CRD) approach in venom allergy. Already to date, CRD has increased the sensitivity of sIgE detection and enabled the discrimination between primary sensitization and cross‐reactivity, particularly in patients with sensitization to both honeybee and vespid venom. Hence, CRD in many patients improves the selection of the appropriate immunotherapeutic intervention. Moreover, the detailed knowledge about sensitization profiles on a molecular level might open new options to identify patients who are at increased risk of side‐effects or not to respond to immunotherapy. Therefore, increasing potential of CRD becomes evident, to direct therapeutic decisions in a personalized and patient‐tailored manner. Reviewed here are the state of the art options, recent developments and future perspectives of CRD of Hymenoptera venom allergy.