Myocardial infarction (MI) is the most common cause of cardiac injury in the Western world. Cardiac injury activates innate immune mechanisms initiating an inflammatory reaction. Inflammatory ...cytokines and vascular cell adhesion molecules (VCAM) promote adhesive interactions between leukocytes and endothelial cells, resulting in the transmigration of inflammatory cells into the site of injury. Low vitamin D levels are associated with higher prevalence of cardiovascular risk factors and a higher risk of MI. In this paper, we examine the effects of short-term vitamin D supplementation on inflammatory cytokine levels after an acute coronary syndrome. We recruited patients arriving to the hospital with an acute MI. All patients received optimal medical therapy and underwent a coronary catheterization. Half of the patients were randomly selected and treated with a daily supplement of vitamin D (4,000 IU) for 5 days. A short course of treatment with vitamin D effectively attenuated the increase in circulating levels of inflammatory cytokines after an acute coronary event. Control group patients had increased cytokine and cellular adhesion molecules serum concentrations after 5 days, while the vitamin D-treated group had an attenuated elevation or a reduction of these parameters. There were significant differences in VCAM-1 levels, C-reactive protein, and interleukin-6. There were trends toward significance in interleukin-8 levels. There were no significant differences in circulating levels of intercellular adhesion molecule 1, E-selectin, vascular endothelial growth factor, and tumor necrosis factor-α. These findings provide information on the anti-inflammatory effects of vitamin D on the vascular system and suggest mechanisms that mediate some of its cardioprotective properties. There is place for further studies involving prolonged vitamin D treatment in patients suffering from ischemic heart disease.
Vitamin D is increasingly associated with the pathology of cognition and mental illness. Vitamin D receptors have been detected on neurons that regulate behavior.
To assess vitamin D serum ...concentrations in patients with major depression and schizophrenia as compared to healthy controls and to determine if a correlation exists between serum levels of vitamin D and disease activity.
We recruited 50 patients with schizophrenia and compared them to 33 patients with major depression and 50 controls with no major psychopathology. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia and the Hamilton Depression scale for depression were administered on the same day the blood samples were drawn. We used LIAISON 25-OH vitamin D (DiaSorin) immunoassay to measure serum concentrations of 25-OH vitamin D.
Lower serum vitamin D concentrations were detected among patients with schizophrenia (15.0 +/- 7.3 ng/ml) compared to patients with depression (19.6 +/- 8.3 ng/ml) and to controls (20.2 +/- 7.8 ng/ml, P < 0.05). We found no correlation between disease activity, measured by the PANSS score, and vitamin D levels.
Serum vitamin D levels were lower in patients with schizophrenia as compared to patients with depression and to healthy controls. No correlation was found between serum concentration and disease activity. Additional studies are needed to elucidate the role of vitamin D in the autoimmune mechanism and in the pathogenesis of schizophrenia.
The Oriental hornet
Vespa orientalis (Hymenoptera, Vespinae) coordinates its daily activities (e.g. flights out of the nest associated with digging activities and removal of the dug soil from the ...nest) with the amount of insolation. Thus, the stronger the insolation, the more intense the flight activity and vise versa. The hornet's cuticle bears a few yellow stripes interposed among brown parts of the gastral cuticle. These yellow stripes are composed of two elements, namely, a transparent cuticle and underneath it a layer of yellow granules. When the hornets are exposed to UV light, the layer containing the yellow granules is less active than in hornets kept in the dark. This diminished activity entails a lower production of glucose as well as of several enzymes prevalent also in the liver of mammals, like creatine kinase, alanine aminotransferase, aspartate transaminase. Thus solar irradiation stimulates and produces a change in the metabolic activities of the hornet. The fact that hornets link their flight activity with the insolation leads us to speculate that the sun contributes energetically to the hornet's activity.
To assess whether elevated levels of estriol (E
3) in pregnancy are a factor in the fetal environment associated with undescended testes, we carried out a two-part study: case-control followed by a ...retrospective cohort study on cryptorchid boys born in the Sapir Medical Center (Kfar Saba, Israel). We found significantly lower pregnancy urinary E
3 levels in cryptorchid newborns as compared to controls; however, subgroup comparison yielded significantly higher pregnancy unconjugated E
3 levels in the infants who underwent orchiopexy as compared to those who did not.
Monoclonal gammopathy of undetermined significance is defined by the presence of: low serum and/or urine monoclonal protein level; less than 10% plasma cells in bone marrow; normal serum calcium, ...creatinine and hemoglobinlevels; and no bone lesions on full skeletal X-ray survey.
To study the necessity of bone marrow examination for the diagnosis and clinical course of MGUS.
We retrospectively screened the medical records of all patients in whom monoclonal protein was found in the serum during 2001-2002 in the medical laboratories of Meir Medical Center. Asymptomatic patients who had serum monoclonal immunoglobulin G < 3.0 g/dl or IgA < 2.0 g/dl or IgM < 1.0 g/dl without anemia, renal failure, hypercalcemia or any bone lesions on skeletal survey were eligible. Full records of patients who were evaluated in the hematology clinic were available (group 1). The remaining patients were followed by their family physicians; thus we had access only to their electronic files including laboratory results and new diagnoses (group 2). Demographic and clinical parameters as well as clinical course werewere evaluated.
Both groups (57 and 255 patients, respectively) had similar demographic, laboratory and clinical characteristics. Bone marrow examination was performed in 30 of 57 patients (group 1): 16 were normal, 8 had an excess of normal plasma cells, and 6 had excess of pathologic plasma cells. However, only in two of the latter six could a diagnosis of multiple myeloma be established. All group 1 patients were followed for 22 +/- 11 months and onlytwo developed overt multiple myeloma. During the same period, 6 of 255 patients (group 2) were diagnosed as multiple myeloma and 3 as MGUS in other hospitals. The rest had a stable course with no change in their laboratory values.
Our findings suggest that bone marrow examination should not be performed routinely in patients who fulfill strict clinical and laboratory criteria of MGUS.
The significance of the glycosylphosphatidylinositol (GPI) anchor is unknown. Since GPI-anchored proteins mediate signaling, it has been suggested that the GPI structure serves as a ...signal-transducing element. However, the division of signaling functions between transmembrane and GPI-anchored proteins is unclear. Studies of distinct membrane-anchored forms of the same protein may resolve this issue. The adhesion molecule CD58 is expressed on the cell surface in both a transmembrane and a GPI-anchored form and hence provides a useful model. We studied CD58 in the human B lymphoblastoid cell line JY. In addition to mediating adhesion, CD58 is involved in signal transduction. Incubation of JY cells with immobilized anti-CD58 Abs results in extensive tyrosine phosphorylation and in secretion of TNF-alpha. We demonstrate that CD58 is associated with protein kinase(s) and with several kinase substrates. We further demonstrate that both CD58 isoforms are involved. CD58 in JY variant cells, which express only the transmembrane form, as well as CD58 in JY variant cells, which express only the GPI-anchored form, are associated with kinase activity. This association results in a phosphorylation pattern that is common to the variant and to wild-type JY cells. Thus, these findings suggest that the capacity of GPI-anchored proteins to interact with kinases is not always dependent on the GPI anchor itself.
In this study we describe two patients with congenital absence of alpha-fetoprotein (AFP). The pathological examination results, including an immunohistochemical stain, which define qualitatively the ...levels of AFP detected by the biochemical studies and the comparative genomic hybridization (CGH) are enclosed. A description of the suggested functions of AFP and the means of its production are set forth. An explanation is suggested for the lack of symptoms in a newborn with undetectable levels of AFP and the mechanism by which this condition might occur.
The adhesion molecule CD58 is expressed on the cell surface in both a transmembrane form and a glycosylphosphatidylinositol (GPI)-anchored form. Here we report that CD58 is released from JY cells ...following cross-linking by immobilized anti-CD58 monoclonal antibodies. Antibodies to other cell surface proteins, as well as PMA and LPS, did not trigger CD58 release. The release resulted from membrane cleavage, since biotin-labeled CD58 was released from biotinylated cells, and down-modulation of CD58 surface expression accompanied accumulation of soluble CD58 in culture media. We have previously reported the isolation of JY variant cells, which lack expression of GPI-anchored proteins and thus express only the transmembrane form of CD58. Here we show that these variant cells release CD58 upon crosslinking, indicating that the transmembrane isoform is released, probably by proteolysis. Antibodies directed to the cytoplasmic domain of CD58, in contrast to antibodies against an extracellular epitope of CD58, did not react with released CD58, supporting a membrane cleavage mechanism. It is also shown that CD58, released from 3Hethanolamine-labeled JY cells, contained ethanolamine. This result demonstrates that the GPI-anchored CD58 can be released in parallel to the transmembrane isoform and that this release does not result from proteolytic cleavage, since cleavage by a protease would have removed the ethanolamine. The present data suggest that the two isoforms of CD58 are released upon antibody binding and that their release is mediated by distinct mechanisms.
The effect of persistent measles virus infection on the expression of major histocompatibility complex (MHC) class I antigens was studied. Mouse neuroblastoma cells C1300, clone NS20Y, were ...persistently infected with the Edmonston strain of measles virus. The persistently infected cell line, NS20Y/MS, expressed augmented levels of both H-2Kk and H-2Dd MHC class I glycoproteins. Activation of two interferon(IFN)-induced enzymes, known to be part of the IFN system: (2'-5')oligoadenylate synthetase and double-stranded-RNA-activated protein kinase, was detected. Measles-virus-infected cells elicited cytotoxic T lymphocytes that recognized and lysed virus-infected and uninfected neuroblastoma cells in an H-2-restricted fashion. Furthermore, immunization of mice with persistently infected cells conferred resistance to tumor growth after challenge with the highly malignant NS20Y cells. The rationale for using measles virus for immunotherapy is that most patients develop lifelong immunity after recovery or vaccination from this infection. Patients developing cancer are likely to have memory cells. A secondary response induced by measles-virus-infected cells may therefore induce an efficient immune response against non-infected tumour cells.
