Fulltext search in archive

Tyrosine kinase (TK) activity in primary mononuclear blood cells (MNBC) derived from chronic myelogenous leukemia (CML) patients in the chronic phase as well as from healthy donors was measured by a sensitive time-resolved fluorescence method using the Delfia® Tyrosine Kinase kit. The level of phosphotyrosine was assessed in parallel by flow-cytometry. The experimental protocol for Delfia® was optimized using a K562 cell line. A large part (20 to 50%) of the fluorescence signal from K562 cells was sensitive to Imatinib mesylate, an inhibitor of Bcr-Abl tyrosine kinase, which is currently the leading drug in CML treatment. In primary MNBC, the direct contribution of Bcr-Abl itself to the signal was low. However, a 48h treatment of MNBC with 5 μM Imatinib resulted in a significant reduction of the observed TK activity (mean TK activity value: 56% of control) paralleled by a decrease in the phosphotyrosine level in the CML group. Modification of TK activity by Imatinib was observed also in the donor group. Imatinib mesylate thus probably affects cell signalization even in Bcr-Abl negative cells.

Cell shape, adhesion, and motility are affected by Ca-regulated pathways, which depend on Ca-binding proteins. One such protein is calreticulin, a ubiquitous and major Ca-binding protein, resident in the ER of eukaryotic cells. In the lumen of the ER, calreticulin is a lectin-like chaperone, sharing this function with an ER-membrane protein, calnexin. Calreticulin also functions as an ER-lumenal Ca store and plays a central role in intracellular Ca homeostasis, including the regulation of store-operated Ca influx via plasma membrane and ER Ca channels. Calreticulin also affects processes outside of the ER; most notably, it modulates expression of several genes, some of them adhesion related, such as vinculin and fibronectin. Curiously, changes in the expression level of calreticulin strongly affect tyrosine phosphorylation of cellular proteins, which is known to affect many adhesion-related functions. Consequently, calreticulin affects cell adhesion via the regulation of expression of proteins important in adhesion, as well as via its effects on intracellular signalling pathways. One of the proteins differentially phosphorylated in a calreticulin-dependent manner is β-catenin, a structural component of cadherin-mediated adhesion complexes and a part of the Wnt signalling pathway. We suggest that the observed changes in cell adhesiveness may be due to calreticulin's influence on a signalling pathway from the ER, which includes the β-catenin/vinculin protein system. Differential expression of calreticulin may affect the phosphorylation status of β-catenin by either inhibition of specific phosphotyrosine kinase(s) or activation of phosphotyrosine phosphatase(s). This is likely to affect the balance between complexed and free β-catenin and impinge further down on the Wnt signalling. At present, the mechanism by which calreticulin affects gene expression can only be speculated upon, but our data indicate that calreticulin, via its effects on Ca release from the ER, may indirectly control the expression of several genes by interfering with calcineurin activity and the ability of the transcription factor, NFAT-3, to translocate to the nucleus. The activation of calcineurin depends on the sustained release of Ca from ER stores, which is dependent on calreticulin.
In summary, we propose that calreticulin may be a centrally located connector molecule in a signalling network in the lumen of the ER. Calreticulin is uniquely endowed for such regulation because it is a multifunctional protein that interacts with several other ER proteins in a Ca-dependent manner, suggesting that it may function as a signalling "toggle switch". We therefore hypothesize that calreticulin regulates gene expression by participating in an "ER-to-nucleus" signalling pathway, which parallels an "ER-to-cell surface" pathway based upon post-translational events.

The authors investigated whether cytosolic free calcium concentration ([Ca²⁺]c) plays a role in hydrogen peroxide-induced pancreatic acinar AR42J cells apoptosis. We analysed mitochondrial depolarization, [Ca²⁺]c determination and caspase-3 activity by fluorimetric methods, and cytochrome c release by subcellular fractionation and western blotting. The data shown that hydrogen peroxide, which causes a sustained [Ca²⁺]c increase, induces mitochondrial depolarization and cytochrome c release, and activation of caspase-3. Dimethyl-BAPTA loading did not affect hydrogen peroxide-evoked mitochondrial apoptosis, suggesting that these responses are independent of increases in [Ca²⁺]c. Treatment with thapsigargin, to induce extensive calcium store depletion and subsequent increases in [Ca²⁺]c, also stimulates mitochondrial depolarization cytochrome c release, and caspase-3 activation. Similar results were observed in AR42J cells loaded with dimethyl-BAPTA, suggesting that activation of apoptosis by thapsigargin does not require rises in [Ca²⁺]c. However, the blockade of mitochondrial calcium entry by pretreating with Ru360 showed protection against hydrogen peroxide- and thapsigargin-induced mitochondrial apoptosis. These results indicate that the apoptosis evoked by hydrogen peroxide and thapsigargin is mediated by mitochondrial calcium uptake.

Nanotechnology is an emerging field of science which is producing nano-sized materials. Some nanomaterials are having a significant impact in health care. Of these, carbon nanotubes (CNTs) represent one of the most promising materials in the field of nano-science and technology. Their potential in industrial applications has brought them much attention and the wide spectrum of usage has made it imperative that the impact of CNTs on human health and the environment is investigated thoroughly. In addition to their various beneficial applications, there is a potential for hazardous effects on human health. For example, the potential hazards through inhalation of CNTs have not been sufficiently evaluated. CNTs produce reactive oxygen species (ROS) which are associated with diminishing cellular activities, such as a decrease in the mitochondrial membrane potential etc. This paper reviews the hazardous influence of CNTs on human health and the environment. Specifically, the effects of CNTs on lung toxicity, skin irritation and CNTs cytotoxicity on various cell lines are reviewed. Biomedical applications and biocompatibility of carbon nanotubes are also summarized.

Circadian rhythms, rhythms of about 24 h in various physiological functions, are getting extensively characterized at the molecular level. The generation of circadian rhythms is acknowledged to originate from oscillations in the expression of several clock genes as well as in the regulation of their protein products. While the general entrainment of organisms to the light-dark cycle of the environment is mainly achieved through the master clock of the suprachiasmatic nucleus in mammals, the molecular clockwork is functional in various organs and tissues. The molecular components of the circadian system have been found to be essential for a diversity of basic and homeostatic systems ranging from the control of cell cycle, the regulation of cardiac and metabolic function, to the fine-tuning of sleep and mental health. The present review will focus on the involvement of clock genes in human health and diseases.

Apigenin is a member of the flavone family of flavonoids and possesses anti-inflammatory, free radical scavenging and anti-carcinogenic properties. Hydrogen peroxide, which is generated during oxidative stress, is known to damage proteins, nucleic acids and cell membranes and also has been implicated in cancer, ageing and several chronic neurogenerative diseases. The present study focuses on the protective effect of apigenin against genotoxic doses of hydrogen peroxide (H₂O₂) using sister chromatid exchanges (SCEs) and cytokinesis blocked micronucleus (CBMN) assay. The treatment with 50, 100 and 150 μM of H₂O₂ results in a significant dose dependent increase in the frequency of SCEs and MN. The treatment with 100 μM of H₂O₂ along with 5, 10 and 20 μM of apigenin results in a dose dependent significant decrease in the frequency of SCEs and MN on cultured human lymphocytes. A similar result was obtained with treatment with 150 μM of H₂O₂ along with 5, 10 and 20 μM of apigenin. The results of the present study suggest a protective effect of apigenin against hydrogen peroxide induced genotoxic damage on cultured human lymphocytes.

The ubiquitous polyamines putrescine, spermidine and spermine fulfil an array of physiological roles in man. In particular, their participation in cell growth and proliferation has been of great interest in relation to their roles in tumour growth and in wound healing. Both endogenous and dietary polyamines take part in such processes. The deprivation of exogenous polyamines emerges as a promising strategy in tumour therapy. Thus, reliable information on their content in foods is needed for dieticians. This review continues our previous comprehensive review on the topic, summarising data on the polyamine content in foods published from 2005 to April 2009. Some new data has appeared. Bovine, porcine and chicken liver, kidney, spleen and heart all have a high content of spermine; bovine liver also of spermidine. Losses of spermidine and spermine up to one half of their original levels occur during both cold and frozen storage and during various thermal treatments. Cultivated mushrooms were reported to contain very high levels of spermidine. Recent results have proved that polyamine content varies widely within a food item, and this complicates the application of available data for the controlled nutrition of patients.

The present study was undertaken to provide more information of the translocation of AgNORs to the nucleolar periphery in human early granulocyte progenitors such as myeloblasts and promyelocytes. The bone marrow smears of patients untreated or treated with the cytostatic therapy appeared to be a convenient model for such study because they possessed a satisfactory number of these cells. The translocation of AgNORs to the nucleolar periphery in early granulocytic progenitors was observed in all studied patients but with different incidence. Since the translocation of AgNORs to the nucleolar periphery was induced in experimental studies in vitro by the cell ageing, it seems to be likely that even some granulocyte progenitors in patients suffering from chronic myeloid leukaemia might age without a further differentiation. In addition, the incidence of such cells was markedly and significantly increased by the targeted cytostatic therapy with imatinib. At this occasion it should be noted that these patients were also characterised by a significantly decreased granulopoiesis.

Six clinically healthy blood donor dogs were used to evaluate the effect of desmopressin (DDAVP) on haemochromocytometric and clotting parameters,. They received subcutaneously a physiological solution (placebo) and DDAVP (1μg/kg) with a two-weeks wash-out period between treatments. Blood samples were collected immediately before the injection, after 30 minutes, then after 1, 2, 3, 4, 5 and 6 hours. Two-way repeated measure analysis of variance (ANOVA) showed no significant effect of DDAVP vs placebo, except for white blood cell (WBC) count, and in particular on neutrophils. In conclusion, DDAVP administration in healthy donor dogs does not induce modification in blood cell count and clotting parameters, except of WBC.

Estrogen replacement therapy (ERT) engenders much debate since several studies contradict its efficacy as a palliative therapy for cognitive decline and neurodegenerative diseases. Signaling transduction pathways alter brain cell activity, survival, and morphology by facilitating transcription factor activation and protein production. The steroidal hormone estrogen and the anti-depressant drug lithium can interact also through these signaling transduction pathways resulting in transcription factor activation. The transcription factor cAMP response element binding protein (CREB) is affected by both estrogen and lithium, and CREB regulates genes involved in learning, memory and neuronal survival. CREB is activated upon phosphorylation at serine 133 by protein kinases and, estrogen and its receptors (ER) facilitate this phosphorylation. Glycogen synthase kinase-3beta (GSK-3β) attenuates CREB's transcriptional properties via subsequent phosphorylation of its serine 129, and lithium is known as a negative regulator of GSK-3β, thus facilitating CREB response element binding. Interestingly, ERα function and DNA-binding properties are facilitated by GSK-3β. In this review we include protein modeling depicting the interaction of CREB/GSK-3β and ERα/GSK-3β using I-TASSER and PatchDock web servers. Understanding the molecular pathways of estrogen will assist in identifying a palliative therapy for menopause-related dementia, and lithium may serve this purpose by acting as a selective estrogen-mediated signaling modulator.

The nucleolus is a large nuclear domain generated by the act of building ribosomes. It illustrates the compartmentation of the nuclear functions, since it is in the nucleolus that transcription of the ribosomal genes, maturation and processing of the 47S ribosomal RNAs (rRNAs) into 18S, 5.8S and 28S rRNA, and almost complete assembly of the 40S and 60S ribosome subunits take place. The shape, size and organization of the nucleoli vary with their activity. Nuleolar activity is a cell cycle dependent-process. In electron microscopy, the nucleolus exhibits three main components: fibrillar centers (FCs), a dense fibrillar component (DFC) and a granular component (GC), corresponding to different steps of ribosome biogenesis. The steady state between transcription, processing and export of ribosomal subunits engenders this organization. Conversely, inactivation or blockage of one of these processes modifies the organization of the nucleolus and ultimately induces nucleolar disassembly. The nucleolus is also a plurifunctional domain, a key partner of chromatin architecture in the nucleus and it plays a crucial role in several cellular functions in addition to ribosome production.
The nucleolus is assembled at the end of mitosis, is active during interphase, and disassembled in prophase. The nucleolar transcription and processing machineries are inherited from parental to daughter cells through mitosis. The polymerase I (pol I) transcription machinery is repressed during mitosis although assembled with ribosomal genes. Repression of pol I transcription is achieved at the end of prophase and is maintained during mitosis through phosphorylation of transcription factors by the cyclin-dependent kinase (CDK) 1. The nucleolar processing machineries relocalize from the nucleolus towards the periphery of all chromosomes until telophase and this chromosome association depends on CDK1 activity. As a consequence of natural inhibition of CDK1 activity, pol I transcription is restored in telophase. The processing machineries are recruited to the sites of rDNA transcription after a temporary transit in foci known as prenucleolar bodies.
In conclusion, the behavior of the nucleolus illustrates the fact that the dynamics of nuclear organization are integrated in a network of interactions and controls that is largely dependent on the coordination of cell cycle controls.

Nitric oxide (NO) is a free radical endogenously produced by nitric oxide synthase. This molecule possesses many important functions in the mammalian organism. The role of NO in regulating cell death and proliferation is now widely recognized. In cultured primary hepatocytes both proapoptotic and antiapoptotic NO effects have been reported. However, most reports support its role in the inhibition of apoptosis. NO has been shown to suppress apoptosis in a model of inflammation and cholestasis, and inhibits spontaneous apoptosis. NO antiapoptotic function was exerted via inhibition of both activity and activation of caspases either directly by nitrosylation, or indirectly via an cGMP-dependent pathway. Both spontaneous and induced hepatocyte apoptosis can be determined by biochemical and morphological methods, which cover various aspects of the apoptotic process, and have a different specificity for detection of apoptotic cell death.

The effects of irradiation (200kV X-ray, 5 Gy), extremely low frequency electromagnetic fields (ELF-EMF, 50 Hz, 60±0.2 μT) and/or heat shock (HS, 41°C for 30 min) on the expression of several heat shock genes (HSP27, HSP60, HSP70, HSP75, HSP78, HSP90) in human HL-60 leukaemia cells was studied by RT-PCR. In addition, the effects of these stressors on cell cycle progression in exponentially and asynchronously growing cell cultures were studied by flow cytometry. The dynamics of cell division during successive cell cycles was monitored by fluorescence-labelling of the cells with carboxyfluorescein succinimidyl ester (CFSE). Finally, the cell cycle distribution was studied by staining with propidium iodide (PI). With respect to HSP gene expression the three stressors produced similar effects. The combination of stressors (ELF-EMF and HS or Radiation and HS) strongly induced transcription of the HSP70 gene above the level induced by each stressor alone. The cell cycle analysis, however, revealed striking differences in the cellular response to each stressor. Of particular interest was the observed thermoprotective effect of ELF-EMF in heat shocked cells, an effect that was not seen in cells which were exposed to X-rays in the presence of thermal stress.

A significant aspermatogenic activity, ascertained by microscopic studies of seminiferous tubules and interstitial tissue, and by the observation of the entrance of immunity and fibrocytic cells in mice injected with polyspermine (PS) or polyspermine conjugated to monomeric or dimeric RNase A (PS-RNase A or PS-dimeric RNase A, respectively), was found either in mice injected or in non-injected testes. Polyspermine and its complexes with RNase A destroyed all spermatogenic and intertestitial tissue, including Leydic cells, as well as their ability to secrete testosterone. The total loss of spermatogenic activity in injected testes is irreversible because spermatogonia cells also were destroyed. The injection of PS into both mice testes determined the total degeneration of testicle tissue in 50% of injected testes. The second half of testes was also partly degenerated, and if they were re-injected, almost all testes were fully destroyed. PS-dimeric RNase A injected once into both testicles produced a stronger degeneration and also the interruption of testosterone secretion in comparison with the effects due to injection of mice with PS or PS-RNase A. In all mice treated with these substances, as well as in rats in which PS was injected twice into their testes, we detected polymorfonucleates, monocytes, plasma cells, lymphocytes and fibrocytic cells. Antibodies against PS, PS-RNase A or PS-dimeric RNase A did not influence the aspermatogenic activity. Animals in which a repeated intra-peritoneal injection was carried out did not lose body mass and remained in good condition, with the exception of mice injected with spermine.

The epidermal stem cell plays a pivotal role in the function of squamous epithelia in physiological as well as in pathological conditions such as cancer. This review summarizes data about the glycobiology of normal squamous epithelia and related tumors with respect to epithelial cell differentiation and search for a glycophenotype specific for epidermal stem cells using labeled plant and endogenous lectins. Although the glycophenotype typical for epithelial cells at the stage of low differentiation level were found, no typical cell surface saccharidic markers of stem cells were detected. The nuclear binding of galectin-1 seems to be specific for the keratinocyte population prepared from hair follicles enriched for multipotent stem cells. The close topographical relationship of nuclear galectin-1 binding sites with SC35 splicing factor suggests some role for these glycoepitopes in pre-mRNA splicing. The data shown in this paper can be employed for diagnostic purposes and for cell therapy of skin defects and indicate the importance of the use of endogenous lectins as probes in biology and medicine.

Down syndrome (DS) is often accompanied by autoimmune diseases. Among those, autoimmune thyroid disease, type 1 diabetes and celiac disease are the most common. The major cause of enhanced vulnerability of DS patients to a variety of autoimmune diseases is impaired immune response, with multiple abnormalities in all components of the immune system, especially in cell-mediated immunity. This could explain a significantly higher frequency of autoimmune disorders in DS compared to the general population. The diagnosis of autoimmune diseases accompanying DS could be complicated by masking effects of the underlying features of the syndrome such as failure to thrive, short stature and delayed puberty. However, screening for immunological signs of coexistent autoimmunity such as tissue-specific antibodies and monitoring insulin secretion, glucose levels, thyroid function and other metabolic parameters should help in early diagnosis of coexistent autoimmunity in DS patiens.

Phenylhydrazine (PHZ) and its derivatives were first given a medical application at the end of the 19^th century but with very little benefit. However, this compound seems to be very useful in models studying mechanisms of haemolytic anaemia. Phenylhydrazine induces a reactive oxygen species formation, peroxidation of lipids and oxidative degradation of spectrin in the membrane skeleton. PHZ-induced haemolytic injury seems to be derived from oxidative alternations to red blood cell proteins. This compound can modulate immune reactions.

The editorial boards with responsible reviewers in scientific journals might play a very important role and should be of a great help for authors. It is a reasonable hope that the journals with such reviewers might be very much respected as well as and highly evaluated without overestimation of the impact factor.

As more information accumulates on the detailed dynamics of life processes, emphasis on steady state behaviour gives way to the recognition that the organism is a multi-oscillator. Systems biology takes account of the controls and balances on inputs and outputs between the environment and the open system of the functioning organism. The matching of the system to its periodic environment performed by biological clocks (circadian, tidal, lunar, annual) is belatedly acknowledged and exploited in applied biomedicine, even as detailed mechanisms continue to be elucidated. Ancestral shorter-period (ultradian) oscillations, rhythms and clocks are all-pervasive in intracellular regulation and control. Yeast in continuous culture shows all these characteristics as well as population coherence. Temporal organisation of tissues, organs and of the whole organism; its construction, operation and maintenance are extensions of these dynamic principles.

For the psychiatrist, lithium is an effective drug for both the treatment and prophylaxis of bipolar disorder. The molecular mechanisms underlying its therapeutic actions have not yet been fully explained. The effects of lithium on a number of enzymes and biological processes have been studied. Inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) have been suggested as the relevant intracellular targets for lithium action. The discovery of the role of GSK-3, the Wnt signalling system, and the anti-apoptotic factor Bcl-2 has led to the suggestion that there could be a therapeutic use for lithium in neurodegenerative disorders, such as Alzheimer's disease.

Calreticulin is a Ca²⁺-binding protein of the ER/SR, from where it acts as a chaperone, and affects calcium homeostasis, gene expression and cell adhesion. Cell adhesion to the extracellular matrix can generate transmembrane signals important for cell survival and migration. In a variety of cell types, integrin stimulation by ECM proteins, such as fibronectin, leads to changes in intracellular protein tyrosine phosphorylation. Tyrosine phosphorylation leads to the co-localization of focal adhesion kinase, vinculin and paxillin at focal contacts. Interaction between focal adhesion kinase and paxillin is critical for the activation of signaling cascades involved in cell survival and motility. Fibroblasts either over- or underexpressing calreticulin show differences in their adhesive properties, which are related to the calmodulin/CaMKII pathway. Inhibition of these pathways causes the weekly adhesive calreticulin underexpressing cells to behave like the calreticulin overexpressers, through increased spreading and increased levels of focal adhesion kinase, paxillin and fibronectin. We propose that calreticulin, via its Ca²⁺-homeostatic effects, may affect fibronectin synthesis and matrix assembly by modulating fibronectin gene expression, and by influencing formation of cellular adhesions, both of which are instrumental in matrix assembly and remodelling. Interestingly, it appears that besides the calmodulin/CaMKII pathway, differential calreticulin expression also modulates the c-src pathway.

We tested the potency to reactivate AChE inhibited by diisopropyl fluorophosphates (DFP) by using bis-pyridinium oxime reactivators connected with CH₂CH₂OCH₂CH₂ linkers between two pyridinium rings. The potency was strongly dependent on oxime functional groups, and the bis-oxime derivatives 1,1-[Oxybis(ethylene)]-bis[4-(hydroxyimino)methyl]pyridinium dibromide (1) and 1,1-[Oxybis(ethylene)]-bis[2-(hydroxyimino)methyl]pyridinium dichloride (2) are more potent than mono-oxime compounds 1-(4-hydroxyiminomethyl-1-pyridino)-5-(4-carbamoyl-1-pyridino)-3-oxapentane dibromide (3) and 1-(3-hydroxyiminomethyl-1-pyridino)-5-(4-carbamoyl-1-pyridino)-3-oxapentane dibromide (4). Not only is the number of oxime groups an important structural factor, but also their position. The in vitro reactivation ability of the most potent bis-pyridinium oxime 2 was further evaluated for the housefly (HF) AChE inhibited by DFP and the bovine red blood cell (RBC) AChE inhibited by paraoxon. The reactivation ability of oxime 2 at 5x10^-3M concentration was almost 80% for HF-AChE inhibited by DFP and 82.1% for RBC-AChE inhibited by paraoxon.

B-chronic lymphocytic leukemia (B-CLL) is the most common form of leukemia in the western world. It results from a relentless accumulation of small mature monoclonal lymphocytes. Following a recent demonstration of a significant increase in the proliferative pool of CLL cells in vivo, the gradual accumulation of malignant B-CLL cells seems to be primarily the consequence of their selective survival advantages relative to their normal B-cell counterparts. As the disease is mainly caused by defective apoptosis it is thus a good candidate for treatment by proapoptotic agents. Even though a large amount of research has been done during the last past years, the prognosis has not changed. Because of this, new therapeutic strategies are urgently needed, especially those that could switch on new apoptotic responses. In order to test the ability of parthenolide, a sesquiterpene lactone, to induce apoptosis and cytotoxicity of B-CLL cells in vitro, we cultured these cells in the presence of this substance. Incubations were continued for 3 days. Samples of cells were taken from cultures at 0, 24, 48 and 72 hours to measure apoptosis and cell viability. Peripheral Blood Mononuclear Cells (PBMCs) from five normal donors were submitted to the same techniques and served as control samples. In this study we show for the first time that parthenolide has a potent apoptotic and cytotoxic effect on B-CLL. It is noteworthy that this substance has almost no impact on normal PBMCs. This evidence suggests that parthenolide might be a promising therapy for B-CLL.

Rhythmic changes in a number of haematological characteristics have been described in many published papers during the 20^th and at the beginning of the 21^st century. The best known are circadian rhythms, which are mostly correlated with the light/dark regime, inducing rhythmic changes in levels of melatonin, synchronised by a suprachiasmatic nucleus and the retinohypothalamic input. These circadian rhythms in men and diurnal animals have an inverse relationship to rhythms in nocturnal beings. Some haematological rhythms are modified by other synchronisers. Knowledge of circadian rhythms in haematological characteristics is important for both the faultless clinical interpretation of laboratory data and the search for mechanisms participating in rhythm regulation.

Hodgkin's Disease (HD) is one of the malignant diseases with good chances for a cure. The prognosis for cure depends on the initial stages and the outcome after initial treatment. Stages I or II at diagnosis, or a complete remission after initial treatment are good indicators for the best prognosis to patients.
A frequent problem faced by clinicians is met at the post-therapy stage because of the difficulty of distinguishing between dead tissue and disease activity in residual masses. Considering that these two situations include therapy options that run from treatment abstention to autologous stem cell transplantation, it is extremely important to distinguish them accurately.
Classical Tomography Scan (CT Scan), Gallium scintigraphy, Magnetic Resonance Imaging (MRI) or Positron Emission Tomography (PET) are used to investigate residual masses. In order to clarify the best way to confirm the post-treatment status of patients affected by HD, we describe in this paper our experience of using PET to solve those problem situations where a CT Scan or MRI were not conclusive and Gallium was negative.

Quality control of the endoplasmic reticulum plays a critical role in protein folding, modification and modification of a secretory pathway. As endoplasmic reticulum chaperones, calreticulin and calnexin have similar substrate specificity and share several common features. Yet, surprisingly, mice bearing a disruption in the calreticulin gene die from a lesion in cardiac development and develop significant metabolic problems whereas calnexin-deficient mice are born alive with, yet not understood, neurological problems. Studies with calreticulin and calnexin gene knockout mice and calreticulin- and calnexin-deficient cell lines indicate that calnexin is unable to compensate for the loss of calreticulin and conversely, calreticulin cannot compensate for the loss of calnexin. Calreticulin or calnexin deficiency or reduction in the level of ERp57 protein (ERp57 heterozygote mice) leads to development of metabolic disorders as documented by sever changes serum lipids and carbohydrates composition in these animals. These observations indicate that calreticulin, calnexin and ERp57, in addition of being involved in maturation of glycoproteins in the endoplasmic reticulum, perform other distinct functions including affecting energy metabolism.

The present study was undertaken to provide more information on the nucleolar size, number and distribution of AgNORs (silver stained nucleolus organizer regions) in nucleolar bodies of aging leukemic granulocytic progenitor cells represented by cultured K562 cells. In these aging and starving cells without further differentiation and with translocated AgNORs to the nucleolar periphery, the diameter of the nucleolar size was reduced together with a reduction in the number of these nucleolar compartments. However, after re-feeding cell cultures, the nucleolar size increased again. Similarly, the number of AgNORs also increased and was distributed in the whole nucleolar body as in control cells. Such cells apparently entered into the cycle and proliferation documented by the re-occurrence of mitotic divisions in studied cultures, an increased number of AgNORs and increased nuclear size. This observation suggests that early granulocytic precursors with translocated nucleolar AgNORs might represent a transitionally quiescent population of cells which may return to a fully proliferating state.