Is factor V Leiden a risk factor for fetal loss?

A successful pregnancy is dependent on the development of adequate placental circulation. The abnormalities of placental vasculature may result in a number of gestational pathologies, including fetal loss. The aim of our study was to determine whether women with f V Leiden are at an increased risk of pregnancy loss. For this purpose we assessed three groups of women. In a prospective group we examined 30 females with spontaneous abortions for f V Leiden. In a retrospective group we assessed the frequency of abortions in 80 women (172 pregnancies) with f V Leiden (72 heterozygous, 8 homozygous) from 57 unrelated families. In a control group we evaluated the frequency of abortions in 45 women without f V Leiden. Factor V Leiden was found in 3% of women in the 1st group. Fetal loss occurred in 10% of women in the 2nd group and in 9% in the 3rd group. Factor V Leiden was not found to be a risk factor for fetal loss in our study group.     

Synergy between tumour necrosis factor α and granulocyte-macrophage colony-stimulating factor in neutrophil stimulation

We have examined the interaction between the cytokines, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor α (TNFα) on polymorphonuclear leukocyte (PMN) function and on PMN responses to further stimulation with formyl Met Leu Phe (fMLP). Incubation of PMN with TNFα (0.3 nM) and, to a lesser extent, with GM-CSF (1 nM) directly stimulated superoxide anion (O ⁻₂ ) generation and increased the response to subsequent stimulation of PMN by fMLP (100 nM). However, the combination of GM-CSF and TNFα did not result in increased O ⁻₂ generation and there was no synergistic effect of the combination of these cytokines on the priming of fMLP-induced O ⁻₂ generation. The combination of TNFα and GM-CSF did result in a striking synergism in the stimulation of PAF generation, and, whereas neither stimulus alone resulted in detectable PAF release, the combination elicited the release of significant levels of PAF. The observation of significant PAF release from PMN exposed to TNFα and GM-CSF indicates that overt neutrophil stimulation with phagocytic or soluble stimuli may not be required for expression of at least some of the PMN pro-inflammatory capacity.

     

Hemolin-A lepidopteran anti-viral defense factor?

Immunity in insects has largely focused on responses towards bacteria and fungi, but recently the study of immune responses against viral infections has also received attention. In Lepidoptera, phagocytosis and encapsulation mediated by hemocytes, and apoptosis are part of the response against virus infection; however, many studies also suggest the presence of unknown factors involved in the anti-viral defense. An up-regulation of the lepidopteran-specific pattern recognition protein Hemolin after baculovirus infection in the Chinese oak silkmoth and discovery of putative virus responsive elements in the up-stream regions of Hemolin in the Cecropia moth and the Tobacco horn worm could suggest that Hemolin is involved in virus defense. In this paper, a number of studies investigating baculovirus pathogenesis, and others analyzing Hemolin expression have been revisited leading to the speculation that Hemolin could be engaged in several anti-viral processes.     

Platelet-derived growth factor and platelet-derived growth factor receptor-α expression in the normal human thymus and thymoma

Platelet-derived growth factor (PDGF) and its receptors (PDGFRs) are strongly involved in the normal development of several organs, tumour angiogenesis and malignant progression and metastasis. Few studies concerning their expression, distribution and role in normal and pathological human thymus are available in the literature. The aim of this study has been to analyse the immunohistochemical expression of PDGF and PDGFR-α in prenatal and postnatal normal human thymus and thymomal biopsy specimens. The results demonstrated immunoreactivity to both PDGF and PDGFR-α in all specimens, but the intensity, distribution and number of positive cells were different in normal thymus and thymomas, and also among different tumour types. PDGF and PDGFR-α were weakly expressed in foetal and postnatal humans with a different distribution between cortex and medulla in both blood vessels and epithelial cells, whereas they were overexpressed in thymoma, especially in type B2 and B3, in the tumour epithelial cells. Overall, these data suggest that PDGF and PDGFR-α may be involved in the pathophysiology of the human thymus.     

Are epidermal growth factor and transforming growth factor responsible for pseudoepitheliomatous hyperplasia associated with granular cell tumors?

Granular cell tumors (GCT) are uncommon benign neoplasms that have a predilection for the head and neck region. These tumors can frequently be associated with pseudoepitheliomatous hyperplasia (PEH), which in turn may be mistaken for squamous cell carcinoma. Although epidermal growth factors are overexpressed in squamous cell carcinomas of the head and neck, their presence in PEH, especially its relation to GCT, is unknown. We hypothesize that the expression of epidermal growth factor receptor (EGFR), epidermal growth factor (EGF), and transforming growth factor alpha (TGFalpha) in GCT have a role in the development of PEH overlying some GCT. Sections from 13 cases of GCT (five with overlying PEH) were examined histologically and evaluated immunohistochemically using monoclonal antibodies for EGFR, EGF, and TGFalpha. These were compared with nine cases of PEH independent of GCT. Two of five GCT with overlying PEH and two of six GCT without overlying PEH stained positively for TGFalpha. None of the GCT stained with EGFR or EGF. All cases of PEH, whether or not associated with GCT, were reactive for EGFR and EGF. Four of the five cases of PEH overlying GCT stained with TGFalpha. The staining pattern and intensity of all three antibodies were comparable to that of the adjacent normal squamous mucosa. Among the three antibodies, only TGFalpha in GCT appears to be related to the development of PEH. Epidermal growth factor receptor and EGF do not seem to be directly involved. The reason of PEH formation associated with GCT in the absence of growth factors is unknown.     

Patellar tendon length--the factor in patellar instability?

Patellar tendon length has been compared in 42 knees with a history of patellar dislocation, and 51 control knees. A lateral X-ray and a magnetic resonance image (MRI) were taken of each knee. The mean radiological patellar tendon length was 46 mm in the controls and 53 mm in the dislocation group. From MRI images, the mean was 44 mm in controls and 52 mm in the dislocation group. This means that the patellar tendon is significantly (P<0.0001) longer in patients with a history of patellar dislocation on both MRI and X-ray. There is no significant difference (P=0.52) between X-ray and MRI measurements of tendon length. The distance between the tibial plateau and the point of tendon insertion was also measured and found to be 28 and 29 mm in the control and dislocation groups, respectively. There is no significant difference between these two measures (P=0.19). In conclusion, patella alta is caused by a long patellar tendon rather than a low insertion into the tibia. Measuring the length of the patellar tendon using MRI is more specific and more sensitive than the Caton-Deschamps index for patellar instability.     

Nerve growth factor: neurotrophin or cytokine?

Nerve growth factor (NGF) is a neutrophin exerting an important role in the development and functions of the central and peripheral nervous system. However, it has recently been documented that several immune cells - such as mast cells, lymphocytes and eosinophils - produce, store and release NGF. Moreover, NGF high and low affinity receptors are widely expressed in the immune system, thus indicating the potential of responding to this neurotrophin through an autocrine mechanism. In fact, NGF influences development differentiation, chemotaxis and mediator release of inflammatory cells as well as fibroblast activation through a complex network influenced by other pro-inflammatory cytokines. Finally, NGF is increased in biological fluids of several allergic, immune and inflammatory diseases. Data reviewed suggest, therefore, that NGF might also be viewed as a (Th2?) cytokine with a modulatory role in allergic inflammation and tissue remodeling.     

Tumor necrosis factor inhibitors – state of knowledge

Tumor necrosis factor (TNF) is considered a major proinflammatory cytokine, affecting various aspects of the immune reaction. All five TNF inhibitors currently available on the market (i.e., etanercept, infliximab, adalimumab, certolizumab and golimumab) are top sellers, although indicated only in autoimmune diseases, including rheumatoid arthritis, Crohn''s disease and psoriasis. This article briefly discusses the background and place for TNF inhibitors in modern therapy. The main safety aspects of TNF inhibitor administration are described in particular, with special consideration of the available meta-analyses. Finally, perspectives on the next-generation TNF inhibitors and their use in the clinic are given.     

What is the genetic factor in migraine?

Migraine is frequently assumed to have an hereditary origin, but what this hereditary factor is, no one really knows. Researchers are currently trying to find defects in genes which could either cause, or tend towards, the development of migraine. This approach is deemed mistaken for two reasons: firstly, pain, being only a signal of an essential monitoring system, cannot be an inheritable factor on its own without the accompanying physiological or pathological processes which give rise to it; and secondly, physicians, almost universally, fail to examine a large part of the head, viz., the mandible and maxillae and their appendages, before making their diagnoses or providing treatment, thereby contravening the fundamental principle of properly examining patients. It is hereby suggested, and evidence is offered showing that impacted teeth could be the long sought-after 'hereditary' factor causing migraine.