A rare case of urinary bladder leiomyosarcoma accompanied by prostate cancer

Non-urothelial neoplasms of the bladder account for less than 5% of all bladder tumors. Sarcoma constitutes the most usual mesenchymal malignancy of the bladder, with leiomyosarcomas being the most common type of sarcoma in adults. A coexistence of this rare tumor with another malignancy has not been reported, to our knowledge. This report demonstrates a case of high-grade bladder leiomyosarcoma cancer with prostate cancer in a 72-year-old patient. The most striking features of this case include the rapid disease progression that confirms the highly aggressive nature of this uncommon disease.     

Inflammation and autoimmunity caused by a SHP1 mutation depend on IL-1, MyD88, and a microbial trigger

A recessive phenotype called spin (spontaneous inflammation) was induced by N-ethyl-N-nitrosourea (ENU) mutagenesis in C57BL/6J mice. Homozygotes display chronic inflammatory lesions affecting the feet, salivary glands and lungs, and antichromatin antibodies. They are immunocompetent and show enhanced resistance to infection by Listeria monocytogenes. TLR-induced TNF and IL-1 production are normal in macrophages derived from spin mice. The autoinflammatory phenotype of spin mice is fully suppressed by compound homozygosity for Myd88(poc), Irak4(otiose), and Il1r1-null mutations, but not Ticam1(Lps2), Stat1(m1Btlr), or Tnf-null mutations. Both autoimmune and autoinflammatory phenotypes are suppressed when spin homozygotes are derived into a germ-free environment. The spin phenotype was ascribed to a viable hypomorphic allele of Ptpn6, which encodes the tyrosine phosphatase SHP1, mutated in mice with the classical motheaten alleles me and me-v. Inflammation and autoimmunity caused by SHP1 deficiency are thus conditional. The SHP1-deficient phenotype is driven by microbes, which activate TLR signaling pathways to elicit IL-1 production. IL-1 signaling via MyD88 elicits inflammatory disease.     

Catastrophic antiphospholipid syndrome masquerading as ischaemic colitis

We describe a young woman whose initial presentation was dominated by acute diarrhoea. Life-threatening multiorgan failure rapidly ensued and necessitated mechanical ventilation and dialysis treatment. An initially elongated activated partial thromboplastin time prompted further coagulation tests that led to the detection of positive lupus anticoagulant, a highly elevated IgG-anticardiolipin (aCL) antibody titre, and prolonged dilute Russell's viper venom time. Histological examination of samples obtained during endoscopy revealed widespread intestinal thrombotic microangiopathy. In view of these serologic and histologic features, a diagnosis of the malignant variant of the antiphospholipid syndrome (APS), also termed 'catastrophic APS', was established. In spite of this syndrome's grim prognosis, the patient recovered following intensive anticoagulation and adjunct treatment with steroids and immunoglobulins.     

Pivalic acid-induced carnitine deficiency and physical exercise in humans

To study the effect of carnitine depletion on physical working capacity, healthy subjects were administered pivaloyl-conjugated antibiotics for 54 days. The mean carnitine concentration in serum decreased from 35.0 to 3.5 μmol / L, and in muscle from 10 to 4.3 μmol/g noncollagen protein (NCP). Exercise tests were performed before and after 54 days' administration of the drug. At submaximal exercise, there was a slight increase in the concentration of 3-hydroxybutyrate in serum; presumably caused by decreased fatty acid oxidation in the liver. There was also a decreased consumption of muscle glycogen, indicating decreased glycolysis in the skeletal muscle. The muscle presumably had enough energy available, since there was no significant decrease in the concentration of adenosine triphosphate (ATP) and creatine phosphate during exercise. The work at maximal oxygen uptake (V ₂max) and the maximal heart rate were reduced. Since V ₂max is considered dependent on heart function, carnitine depletion seemed to affect cardiac function.     

RELATION OF BLAST CELL SURVIVAL AND PROLIFERATION TO CHEMOTHERAPY RESISTANCE IN AML

We have investigated the in vitro blast cell survival (viability) and drug resistance to cytosine arabinoside (Ara-C), daunorubicin (Dau), mitoxantrone (Mitox) and aclarubicin (Acla) of fresh leukaemic blast cells from 80 patients with newly diagnosed acute myeloid leukaemia (AML) employing the semiautomated colourimetric MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide)-assay. In 15 cases we concurrently investigated the relation between in vitro blast cell survival (MTT assay) and blast cell proliferation (³H-thymidine incorporation) in the presence and absence of myeloid growth factors (GFs) G-CSF, GM-CSF and IL-3 (individually and in combination). A highly significant correlation was found between blast cell survival and blast cell proliferation (r = 0.87, P < 1 × 10^?4). Furthermore, in 40 evaluable adult patients who completed intravenous induction chemotherapy and were evaluable for response to chemotherapy we found a positive correlation between in vitro blast survival (MTT assay) and response to chemotherapy with high blast survival being associated with poor response to chemotherapy (P = 0.05). Moreover, in a multivariate analysis, high blast cell survival was significantly associated with high CD13 expression and monocytic phenotype (P = 0.0003 and P = 0.02, respectively). Furthermore, we found an inverse relationship between the baseline proliferation of the blasts and the magnitude of response to the GFs (P < 0.02), indicating that cells with low baseline proliferation were more readily stimulated by growth factors. Finally, we found a significant correlation between leukaemic cell survival and cellular drug resistance towards Dau (P = 0.001) and Mitox (P = 0.03), but not towards Ara-C (P = 0.68) and Acla (P = 0.13). We conclude that high in vitro leukaemic cell survival is associated with drug resistance in vivo and in vitro, and furthermore is correlated with high blast cell proliferation and some adverse prognostic factors previously identified in AML.     

Evidence for balancing selection operating at the het-c heterokaryon incompatibility locus in a group of filamentous fungi

In filamentous fungi, het loci (for heterokaryon incompatibility) are believed to regulate self/nonself-recognition during vegetative growth. As filamentous fungi grow, hyphal fusion occurs within an individual colony to form a network. Hyphal fusion can occur also between different individuals to form a heterokaryon, in which genetically distinct nuclei occupy a common cytoplasm. However, heterokaryotic cells are viable only if the individuals involved have identical alleles at all het loci. One het locus, het-c, has been characterized at the molecular level in Neurospora crassa and encodes a glycine-rich protein. In an effort to understand the role of this locus in filamentous fungi, we chose to study its evolution by analyzing het-c sequence variability in species within Neurospora and related genera. We determined that the het-c locus was polymorphic in a field population of N. crassa with close to equal frequency of each of the three allelic types. Different species and even genera within the Sordariaceae shared het-c polymorphisms, indicating that these polymorphisms originated in an ancestral species. Finally, an analysis of the het-c specificity region shows a high occurrence of nonsynonymous substitution. The persistence of allelic lineages, the nearly equal allelic distribution within populations, and the high frequency of nonsynonymous substitutions in the het-c specificity region suggest that balancing selection has operated to maintain allelic diversity at het-c. Het-c shares this particular evolutionary characteristic of departing from neutrality with other self/nonself-recognition systems such as major histocompatibility complex loci in mammals and the S (self-incompatibility) locus in angiosperms.     

Plasticity of orientation preference maps in the visual cortex of adult cats

In contrast to the high degree of experience-dependent plasticity usually exhibited by cortical representational maps, a number of experiments performed in visual cortex suggest that the basic layout of orientation preference maps is only barely susceptible to activity-dependent modifications. In fact, most of what we know about activity-dependent plasticity in adults comes from experiments in somatosensory, auditory, or motor cortex. Applying a stimulation protocol that has been proven highly effective in other cortical areas, we demonstrate here that enforced synchronous cortical activity induces major changes of orientation preference maps (OPMs) in adult cats. Combining optical imaging of intrinsic signals and electrophysiological single-cell recordings, we show that a few hours of intracortical microstimulation (ICMS) lead to an enlargement of the cortical representational zone at the ICMS site and an extensive restructuring of the entire OPM layout up to several millimeters away, paralleled by dramatic changes of pinwheel numbers and locations. At the single-cell level, we found that the preferred orientation was shifted toward the orientation of the ICMS site over a region of up to 4 mm. Our results show that manipulating the synchronicity of cortical activity locally without invoking training, attention, or reinforcement, OPMs undergo large-scale reorganization reminiscent of plastic changes observed for nonvisual cortical maps. However, changes were much more widespread and enduring. Such large-scale restructuring of the visual cortical networks indicates a substantial capability for activity-dependent plasticity of adult visual cortex and may provide the basis for cognitive learning processes.