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At least 1,243 records · Page 69Linked to original sources
PubMed2002

Parvovirus B19: a pathogen responsible for more than hematologic disorders.

The clinical and pathomorphological patterns of parvovirus B19 (PVB19)-associated diseases is the result of a balance between virus, host target cells and immune response. It is a characteristic feature of PVB19 that in patients with various other preexisting diseases, e.g., many hemolytic anemias, immune complex-mediated vasculitic disorders, and primary or secondary immunodeficiencies, the underlying diseases can be triggered, aggravated or complicated by severe organ manifestations. Identification of PVB19 by means of routine histology and immunohistology is only given in lytic infections occurring in transient aplastic anemia or nonimmune hydrops fetalis by the detection of viral inclusion bodies in erythroid precursor cells. In all other PVB19-associated diseases, molecular pathological methods must be applied. In this report, quantitative real-time polymerase chain reaction was used to determine the viral load in formalin-fixed and paraffin-embedded tissues derived from various organs. Using in situ hybridization it was demonstrated that endothelial cells of the microcirculatory periphery of the heart and hepatobiliar system in lytic infections are PVB19-specific target cells in children and adults. Because treatment of lytic PVB19 infection has been successfully applied, the pathologist should be alerted to include PVB19 into the diagnostic spectrum of viral disease, especially in immunocompromised patients.

Adult↗
PubMed2001

Role of the kinetochore protein Ndc10 in mitotic checkpoint activation in Saccharomyces cerevisiae.

Mitotic checkpoints delay cell cycle progression in response to alterations in the mitotic apparatus, thus ensuring correct chromosome segregation. While improper spindle orientation activates the Bub2/Bfa1-dependent checkpoint in budding yeast, delaying exit from mitosis, lack of bipolar kinetochore-microtubule attachment activates a signal transduction cascade that prevents both anaphase onset and exit from mitosis by inhibiting the Cdc20/APC (Anaphase Promoting Complex)-mediated proteolysis of securin and inactivation of mitotic cyclin-dependent kinases (CDKs), respectively. Proteolysis of the securin Pdsl is necessary to liberate the separase Esp1, which then triggers sister chromatid separation, whereas inactivation of mitotic CDKs is a prerequisite for exit from mitosis and for starting a new round of DNA replication in the next cell cycle. In budding yeast, this latter checkpoint response involves the proteins Mad1, 2, 3, Bub1 and Bub3, whose vertebrate counterparts localize to unattached kinetochores. Mutations that alter other kinetochore proteins result in mitotic checkpoint activation, while the ndc10-1 mutation not only impairs kinetochore function, but also disrupts the checkpoint response, indicating a role for Ndc10 in this process. Here we present evidence that Ndc10 is not part of the Bub2/Bfa1-dependent pathway, and its role in the checkpoint response might also be different from that of the other Mad and Bub proteins. Indeed, Ndc10, unlike other mitotic checkpoint proteins, is not required for the mitotic block induced by overexpression of the Mpsl protein kinase, which is implicated in mitotic checkpoint control. Furthermore, the delay in mitotic exit caused by non-degradable Pds1, which does not require Mad and Bub proteins, depends on Ndc10 function. We propose that a pathway involving Ndc10 might monitor defects in the mitotic apparatus independently of the Mad and Bub proteins. Since the Espl separase is required for exit from mitosis in both ndc10-1 and nocodazole-treated mad2delta cells, the two signal transduction cascades might ultimately converge on the inactivation of Esp1.

Cell Cycle↗
PubMed2004

Cerebral vasculitis and intracerebral hemorrhage in Henoch-Schönlein purpura treated with plasmapheresis.

Severe neurological complications in Henoch-Schonlein purpura (HSP) are rare. We report a 13-year-old girl with HSP receiving oral steroid therapy for HSP nephritis who presented with acute onset of headache, confusion, and loss of bilateral vision. However, immediate cranial computed tomography showed merely a small intracranial hematoma in the left occipital area, which was not consistent with her clinical manifestations. The subsequent magnetic resonance imaging of the brain demonstrated bilateral, multifocal abnormalities with features consistent with cerebral vasculitis. Therapeutic plasmapheresis was performed immediately and there was rapid clinical improvement. In conclusion, we propose that plasmapheresis is a reliable and effective therapy and may be considered as the first-line treatment in this critical condition to prevent massive intracerebral hemorrhagic complication of this immune complex-mediated cerebral vasculitis leading to irreversible neurological sequelae or mortality.

Adolescent↗
PubMed2005

Glomerulonephritis associated with chronic infection from long-term central venous catheterization.

There have been few reports on immune complex-mediated glomerulonephritis associated with chronic infection from long-term central venous catheterization in adulthood. We report here on a 13-year-old boy with nephritis who exhibited glomerulonephritis that had been induced by the long-term use of central venous catheters, and its resolution after extraction of the central venous catheter. A diagnosis of glomerulonephritis associated with chronic infection caused by long-term central venous catheterization was made, based on the absence of clinical findings after removal of the catheter, hypocomplementemia, pathology findings resembling membranoproliferative glomerulonephritis, and detection of Staphylococcus epidermidis from culture of the removed catheter culture. For clinicians using long-term central venous access for parenteral feeding, rapid catheter exchange is necessary for patients with fever of unknown origin.

Adolescent↗
PubMed2000

Alport-like glomerular changes in a patient with nephrotic syndrome: report of a case.

We report a 17-year-old Saudi girl who presented with nephrotic syndrome at the age of 7 years. A renal biopsy revealed a mildly proliferative immune complex-mediated glomerulonephritis, which on ultrastructural examination revealed prominent thickening of the capillary basement membranes, along with marked splitting and lamellation of lamina densa resembling those seen in Alport syndrome. These changes were even more pronounced in renal biopsies performed 1 and 3 years later, respectively. Thorough clinical evaluations and follow-up of more than 10 years failed to reveal any evidence of Alport syndrome. Review of the literature revealed four similar cases reported previously. Diffuse and prominent Alport-like glomerular changes may rarely be seen in patients with nephrotic syndrome in the absence of Alport syndrome. Pathogenesis of these changes, however, remains to be understood.

Adolescent↗
PubMed2006

Differential regulation of c-Fos and FosB in the rat brain after amygdala kindling.

Members of the inducible transcription factor Fos family, that are part of the AP-1 complex that binds to the corresponding promoter site, are implicated in the regulation of gene transcription after acute and chronic seizures. However, little is known about the temporal expression of the AP-1 transcription factors and if individual proteins composing this complex have distinct roles in development and maintenance of permanent epilepsy. In this study, the AP-1 binding capacity, its content of different Fos proteins, and the anatomical specificity, were analyzed 2 or 18 h after achieving full kindling in rats. The same analysis was performed in fully kindled animal receiving a new stimulus after a 3-week pause to determine the extent of stability of the AP-1 transcription factors. While both c-Fos and FosB were induced in all cortical areas after a single stimulus, only FosB-immunoreactivity remained after 18 h. A single stimulation to kindled animals left undisturbed for 3 weeks induced a long-lasting upregulation of AP-1 binding in the frontal cortex, but not in the hippocampus suggesting a permanent exposure of AP-1 heterocomplexes in the frontal cortex. Supershift assays showed that FosB is the dominant component of the long-term AP-1 complex. It is concluded that the AP-1 binding complex in fully kindled rats is composed of different proteins, and that FosB-containing AP-1 complexes mediate long-term effects in the frontal cortex.

Amygdala↗
PubMed2005

Pathological laughter and behavioural change in childhood pontine glioma.

Children with pontine glioma usually present classically with ataxia, motor deficits and cranial nerve palsies. The pons has generally not been regarded as a structure that mediates complex affective behaviour. However, we report nine children who either at the time of presentation or progression demonstrated marked behavioural changes manifesting as either "pathological laughter" or separation anxiety in the form of school refusal. A mechanism of how pontine lesions can cause such complex affective and cognitive behaviour has been suggested to consist of the disruption of a network of cerebro-ponto-cerebellar pathways and the evidence for this mechanism is discussed.

Anxiety, Separation↗
PubMed2001

Psychosis Due to Neurologic Conditions.

Psychosis arises with considerable frequency in a number of neurologic conditions. The treatment of such patients is often challenging, as many of the treatments for psychosis pose some risk of worsening the underlying neurologic condition. Although psychosis may emerge in the context of any neurologic condition that sufficiently disrupts the functioning of or connections between limbic, paralimbic, frontal, subcortical areas mediating complex sensory perception, interpretation, and thought or language organization, secondary psychoses are most often encountered in patients with Alzheimer's disease (Parkinson's disease receives dopaminomimetic therapies) and epilepsy. Psychosis, and particularly delusions and visual hallucinations, may arise in Alzheimer's disease. Based on the available literature, the first-line therapy for this problem is risperidone 0.5 to 3 mg per day. If this treatment proves unsuccessful, low-dose haloperidol or olanzapine should be considered next. If these treatments prove unsuccessful, quetiapine should then be considered. Finally, clozapine may be useful for treatment-refractory psychosis due to Alzheimer's disease, but due caution is warranted given its considerable anticholinergic properties and potential for worsening cognition in these patients. Although disease-emergent psychosis (paranoid delusions and visual hallucinations) may develop in patients with Parkinson's disease, psychosis due to dopaminomimetic therapy is much more common. When such symptoms develop, the accepted first step is to taper anti-parkinsonian medications were possible. Anticholinergic medications, amantadine, selegiline, and dopamine receptor agonists should be reduced or discontinued, provided that the patient can tolerate changes in motor symptoms attendant to such reductions. When these reductions are not feasible or fail to improve treatment-emergent psychosis, low-dose quetiapine or clozapine may be useful. The greatest body of evidence supports the effectiveness of these treatments and their relative lack of adverse effects on motor function. When psychosis develops in the context of epilepsy, the generally accepted first step is to maximize anticonvulsant therapy in an effort to reduce the possible contribution of electrophysiologic disturbances in the described areas to psychotic symptoms. When interictal psychosis persists despite such adjustments, initiation with low-dose atypical antipsychotics carries the least risk of lowering seizure threshold and should be considered.

Journal Article↗
PubMed1990

A reexamination of the relationship between growth hormone secretion and slow wave sleep using delta wave analysis.

Sleep onset growth hormone secretion is a reliable and reproducible finding in young adults and children. Secretion typically occurs during the first non-REM period of sleep and, despite some evidence to the contrary, growth hormone secretion has frequently been associated with the first period of slow wave sleep. By measuring delta wave activity (0.5-2 Hz) instead of slow wave sleep and, accounting for the within subject variability, it has not been possible to demonstrate a consistent or statistically significant linear relationship between delta wave activity and sleep-related growth hormone secretion. This suggests the presence of more complex mediating factors and the possibility that sleep onset and growth hormone secretion are two separate processes which are independently stimulated by events associated with sleep onset.

Adolescent↗
PubMed1989

Immunohistochemical studies on distribution of GABAA receptor complex in the rat brain using antibody against purified GABAA receptor complex.

The distribution of the gamma-aminobutyric acid (GABA)A receptor/benzodiazepine receptor/Cl- channel complex in the rat brain was examined immunohistochemically using the specific antibody against purified GABAA receptor complex. The immunization of white albino rabbit with purified GABAA receptor complex resulted in the formation of specific antibody as indicated by the immunoprecipitation test. Immunohistochemical examinations using the antiserum on rat brain slices by the peroxidase-antiperoxidase method revealed the presence of the following immunoreactive sites which coincided with a previous report using antibody against L-glutamic acid decarboxylase; ventromedial nucleus of hypothalamus, red nucleus, globus pallidus, zona compacta and zona reticulata of substantia nigra, layers of Purkinje cells and granular cells of cerebellum, layers III-V of cerebral cortex and stratum radiatum of hippocampus. These results strongly suggest that immunohistochemical application of the antibody against the purified GABAA receptor complex is a useful tool for identifying GABAergic neurons having GABAA receptor complex-mediated synapses.

Animals↗
PubMed1986

Expression of human T antigens in interspecies hybridomas.

Interspecies hybrids were constructed by fusing normal human male peripheral blood mononuclear cells with BW5147, a HGPRT- thymoma derived from an AKR mouse. Hybrid cells were selected in HAT media in culture dishes containing 1 X 10(7) human red blood cells. Twelve weeks after fusion, hybridomas were diluted to 10-15 cells/well and characterized for their expression of the human immune cell surface antigens HLA-DR, T3, T4, and T8 using fluorescent microscopy and cytographic analysis. More than 70% of the hybrid colonies expressed human T-cell surface antigens. Moreover the specific human repetitive DNA (ALU) bound to DNA sequences isolated from the hybridomas after Southern transfers. However, the same hybrids did not have a statistically significant increase in their chromosome number when compared to the mouse parent cell line. Several of the hybridomas produced a soluble factor capable of stimulating the growth of the IL-2 restricted murine cell line CTLL-2 and supported DNA synthesis in human peripheral T-cell populations. Panning experiments demonstrated that the IL-2 producing hybridomas could be enriched by selecting for the human T-cell surface antigen T3. The results presented here indicate that mouse X human hybridomas which express a broad range of human lymphocyte markers can be constructed and maintained in continuous culture for extended periods of time. It also appears that the T3-Ti receptor complex mediates the proliferation of T cells through the T3 molecules linkage to the secretion and/or production of IL-2. The usefulness of interspecific T-cell hybrids as an immunogenetic research tool as well as the significance of the mapping data are discussed.

Animals↗
PubMed1995

Preferential block of desensitizing AMPA receptor in hippocampal neurons by gamma-D-glutamylaminomethylsulfonic acid.

The (RS)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolopropionic acid (AMPA)/kainate receptor-channel complex mediates fast components of excitatory synaptic currents in the central nervous system. Distinguishing between these components is a difficult pharmacological task. As was recently reported, gamma-D-glutamylaminomethylsulfonic acid (GAMS) may be a selective kainate receptor antagonist. We have tested this possibility in experiments which were carried out on acutely isolated rat hippocampal neurons. It appeared that 1 mM GAMS first blocked 83 +/- 1% of the fast desensitizing 128 microM AMPA-gated current, but only 38 +/- 6% of the non-desensitizing current component and reached, at higher GAMS concentrations, a plateau at about 50% of the control steady state current level. In contrast to the blocking action of GAMS on AMPA-gated currents, 4-fold higher concentrations of GAMS were needed to block currents elicited by 256 microM kainate application. It is suggested that several subunit compositions of the AMPA-gated receptor could coexist on a single hippocampal cell. Furthermore, GAMS has a certain preference for subunit assemblies which could mediate fast desensitizing and, a portion of, the non-desensitizing current component.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1983

Minireview. The nephrotoxicity of cisplatin.

Cisplatin is a cancer chemotherapeutic agent whose clinical use is complicated by its dose related kidney toxicity. Since the histopathological profile of cisplatin nephrotoxicity appears similar to that of other heavy metals, it has been commonly presumed that cisplatin nephrotoxicity is related to the platinum moiety. However, the delayed time course and development of cisplatin nephrotoxicity is not characteristic of heavy metal nephropathy. Furthermore, cisplatin nephrotoxicity is stereospecific to the cis and not the trans isomer, indicating that the platinum atom is not the proximate nephrotoxicant. It is likely that a metabolite of cisplatin, possibly an aquated and/or hydroxylated complex, mediates the nephrotoxicity of cisplatin.

Acute Kidney Injury↗
PubMed1996

Effects of beta- and gamma-carboline derivatives of DNA topoisomerase activities.

beta-Carbolines, harman (1-methyl-9H-pyrido[3,4-b]indole) and norharman (9H-pyrido[3,4-b]indole) and gamma-carbolines, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-4-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), are present in cooked foods and cigarette smoke. We studied the effects of these heterocyclic amines on the activity of DNA topoisomerases. Trp-P-1 and Trp-P-2 inhibited topoisomerase I (topo I) activity with ED50 values of 1.48 and 1.55 micrograms/ml, respectively, in a relaxation assay. Harman and norharman inhibited topo I activity but with much higher ED50 values, 23.8 and 34.4 micrograms/ml, respectively. Trp-P-1 and Trp-P-2 also inhibited topoisomerase II (topo II) activity at about 50 micrograms/ml, in a decatenation assay. Harman and norharman showed a much lower inhibitory effect on topo II activity. None of these compounds stabilized the cleavable complex mediated by topo II. Trp-P-1 and Trp-P-2 intercalated into DNA at concentrations inhibitory to topoisomerases. We considered that the intercalation with DNA and the inhibition of DNA topoisomerases by heterocyclic amines might be partly related to their inhibition of DNA excision repair and their enhancing effect on UV- or chemically induced mutagenic activity.

Breast Neoplasms↗
PubMed1994

Pulmonary alveolar proteinosis and glomerulonephritis in lysinuric protein intolerance: case reports and autopsy findings of four pediatric patients.

Lysinuric protein intolerance is an autosomal recessive disease caused by defective transport of cationic amino acids. Of the 38 lysinuric protein intolerance patients diagnosed in Finland since 1965, four pediatric patients have died. We describe the clinical courses and autopsy findings for these patients. All patients developed acute respiratory insufficiency. In addition to pulmonary hemorrhages, three of the patients had pulmonary alveolar proteinosis and one had cholesterol granulomas. Three patients had a clinically obvious renal insufficiency, but all four showed histologic signs of immune complex-mediated glomerulonephritis. The patients also developed hepatic insufficiency with fatty degeneration or cirrhosis. All patients showed anemia, thrombocytopenia, and a severe bleeding tendency. The bone marrow of three patients was hypercellular, but the amount of megakaryocytes was decreased in two cases. Amyloid was present in the lymph nodes and the spleen. Bone specimens showed osteoporosis. We conclude that pediatric patients with lysinuric protein intolerance are predisposed to develop pulmonary alveolar proteinosis and glomerulonephritis. They are also at risk of protein malnutrition in the active growth phase, probably due to higher requirements for total nitrogen and amino acids.

Adolescent↗
PubMed1992

Effects of in vivo administration of interferon (IFN)-gamma, anti-IFN-gamma, or anti-interleukin-4 monoclonal antibodies in chronic autoimmune graft-versus-host disease.

These studies examined the role of cytokines in chronic autoimmune graft-versus-host disease (GVHD) in B6D2F1 mice injected with lymphoid cells from DBA/2 mice. Anti-interleukin (IL)-4 and anti-interferon (IFN)-gamma mAb, or IFN-gamma, were used in vivo to modulate B cell hyperactivity and disease. Kinetic experiments showed that, 2-3 weeks after induction, GVH mice had 100x elevated serum IgE, while IgG1 and IgG2a were 10x above normal. Early treatment with anti-IL-4 mAb or IFN-gamma decreased serum IgE and IgG1 and had no effect on IgG2a. Anti-IFN-gamma mAb treatment increased serum IgE and IgG1 while reducing IgG2a. This increase in serum immunoglobulins could be correlated with an increased spontaneous secretion of IL-4, IL-5, and IL-6 in spleen cell cultures from anti-IFN-gamma mAb-treated GVH mice. While neither anti-IFN-gamma nor IFN-gamma treatments altered the disease course, anti-IL-4 treatment delayed proteinuria and death in GVH mice. These observations suggest an important role for IL-4 in immune complex-mediated glomerulonephritis in chronic GVHD.

Analysis of Variance↗
PubMed1995

Acute renal failure associated with immunoglobulin therapy.

Four cases of acute renal failure induced by intravenous immunoglobulin are presented, and the literature on the subject is reviewed. The clinical course varies from asymptomatic serum creatinine elevation to anuric renal failure occurring within days of the institution of therapy, followed by the rapid recovery of renal function after termination of therapy. The renal histology demonstrates severe tubular vacuolization with cellular swelling and preservation of the brush border. Glomerular endothelial, mesangial, and epithelial cells also may demonstrate swelling and vacuolization. There is no evidence for inflammatory or immune complex-mediated etiologies. The immunoglobulins or carbohydrate additives in the preparations appear to have a unique and reversible effect on the glomerular and tubular cell function.

Acute Kidney Injury↗
PubMed1995

The 'LXCXE' hydropathic superfamily of ligands for retinoblastoma protein: a proposal.

The present study reports structural similarities between viral oncoproteins, growth factors belonging to the insulin family, members of the steroid/thyroid receptor superfamily, a D-type cyclin, the Elf-1 transcription factor and Bcl oncoproteins in regions that have been shown or proposed to mediate complex formation of these proteins with the tumor suppressor retinoblastoma protein (RB). This relationship predicts a common intracellular pathway for mitogenic signals and molecules promoting cell survival. Conversely, the structural evidence described here suggests that RB may play a central role both at the boundary between negative and positive cell growth regulation as well as in developmental decisions between cell death and cell survival.

Amino Acid Sequence↗