Breast disease: dynamic spiral MR imaging

The cochleo- and tonotopic organization of the second auditory area (AII) was investigated in cats anaesthetized with pentobarbital using a combination of macro- and microelectrode recording technique. The results obtained following electrical stimulation of the neural fibres innervating different regions of the organ of Corti indicate the existence of two complete representations of the cochlea in area AII: one in the dorsocaudal portion, the other in its ventrorostral portion. These two cortical representations of the cochlea differ in size and spatial orientation. The dorsocaudal projection area extends over a distance of 2.6-3.2 mm from the basal to the apical focus and is arc-shaped. The spatial orientation of cochlea representation within the dorsocaudal region of AII is similar to that described in AI, in that stimulation of the cochlea base results in maximal responses in the more rostral portion of AII and stimulation of the apex evokes cortical responses more caudally. The ventrorostral region within AII is smaller (1.4-2.5 mm length), and has the opposite cochleotopic orientation (base and apex stimulation represented caudally and rostrally, respectively). In both AII zones, there was a proportionally greater cortical representation of basilar membrane than of middle and apical portions. Although two distinct zones with the overall cochleotopic pattern described above were noted in all cats, their precise size and location considerably varied in different animals. Using microelectrode recordings, a cortical tonotopic organization can be observed that was consistent with and expanded on the earlier cochleotopic data. Within the dorsocaudal region of AII, neurons with higher best frequency responses were located in more rostral regions, while those with lower best frequencies were located caudally. An orderly progression of best frequency responses was noted as serial recordings carried out along the full extent of the representation. Neurons within the ventrorostral region of AII also displayed an orderly progression of best frequencies, but in the opposite direction, with higher best frequencies noted more caudally and lower best frequencies more rostrally.     

Capillary electrophoretic study of the complex formation between DNA and cationic surfactants

Due to the growing interest in the use of cationic surfactants for the construction of liposomal genetic delivery systems, the study of complex formation between DNA and quaternary ammonium detergents is of fundamental importance. In this context, we undertook the study of this complex formation using capillary zone electrophoresis (CZE) with suppressed electroosmotic flow, a technique that allowed us to both monitor the change in mobility of DNA as a function of added surfactant in a precise and reproducible manner and evaluate the potential of CZE to reflect the change in hydrodynamic friction upon binding. Nevertheless, CZE must be applied with caution for binding studies where strong cooperativity occurs, because of the presence of peak splitting at concentrations close to the half-point of binding. Also, a comparison between this experiment and Manning's polyelectrolyte transport properties theory on one hand and Tirado and Garcia de la Torre expression for hydrodynamic friction of rod-like molecules on the other hand is given.     

Apolipoprotein(a) enhances platelet responses to the thrombin receptor-activating peptide SFLLRN

Elevated levels of lipoprotein(a) [Lp(a)] are correlated with an increased risk of atherosclerotic disease. We examined the effect of recombinant apolipoprotein(a) [r-apo(a)] and Lp(a) on responses of washed human platelets, prelabeled in the dense granules with [14C]serotonin and suspended in Tyrode's solution, to ADP and the thrombin receptor-activating peptide SFLLRN. No effect of the 17 kringle (K), 12K, or 6K r-apo(a) derivatives (at concentrations of 0.35 and 0.7 micromol/L) or Lp(a) (up to 0.1 micromol/L) on primary ADP-induced platelet aggregation was observed. In contrast, weak platelet responses stimulated by 7.5 micromol/L SFLLRN were significantly enhanced by the r-apo(a) derivatives; eg, 0.7 micromol/L 17K r-apo(a) increased aggregation from 15+/-4% to 58+/-6%, release of [14C]serotonin from 9+/-3% to 36+/-6%, and formation of thromboxane A2, measured as its stable metabolite thromboxane B2, from 7+/-1 to 29+/-5 ng/10(9) platelets (n=3; P<0.04 to 0.015). Significant enhancement of aggregation and release of granule contents was observed at a concentration of 17K r-apo(a) as low as 0.175 micromol/L. Purified Lp(a) (0.25 to 0.1 micromol/L) also enhanced SFLLRN-induced aggregation and release in a dose-dependent manner. Although plasminogen (0.7 and 1.5 micromol/L) and low density lipoprotein (0.025 to 0.1 micromol/L) both exhibited potentiating effects on SFLLRN-mediated platelet aggregation, the magnitude of the responses was less than that observed with either the r-apo(a) derivatives or Lp(a). The enhanced responses of platelets via the protease-activated receptor- thrombin receptor in the presence of Lp(a) may contribute to the increased risk of thromboembolic complications of atherosclerosis associated with this lipoprotein.     

Laboratory abnormalities in thrombotic thrombocytopenic purpura. Canadian Apheresis Group

Thrombotic thrombocytopenic purpura is an uncommon disorder that requires prompt recognition and intervention to prevent death. To date, information regarding the classic laboratory abnormalities in the disease has been derived from small numbers of patients whose laboratory tests have been done at many different sites. We report the laboratory findings in 135 patients who presented with thrombotic thrombocytopenic purpura to 17 Canadian centres. 50 men and 85 women had a mean platelet count of 25.3+/-19.4x10(9)/l. The initial platelet count correlated with mortality; 32% of patients with a platelet count of 20x10(9)/l or less died compared with 18% of patients with a platelet count >20x10(9)/l (P=0.058). The platelet-associated IgG was elevated in 88% at presentation whereas the indirect platelet suspension immunofluorescence test was positive in only 18%, 93% of the sera showed reactivity against platelets following protein blotting. All sera tested also showed reactivity against endothelial cells. Immune complexes were seen in all patients, whereas the platelet aggregating factor was detected in 59%. Although the von Willebrand factor was elevated in the majority of patients at entry, the multimer pattern was variable and showed no predictive pattern. Renal dysfunction was common (18%).     

Crossing the boundary: changing mental models in the service of improvement

Two new cell lines, designated NMS-2 and NMS-2PC, were established in vitro from a malignant peripheral nerve sheath tumour (MPNST) in the right thigh and a retroperitoneal lesion of a 30-year-old man with neurofibromatosis type 1 (NF1). The NMS-2 cell line was derived from the first tumour, and the NMS-2PC cell line from a retroperitoneal metastatic tumour detected 9 months later. Cultured NMS-2 cells showed epithelioid features, while NMS-2PC cells showed fibroblast-like features. However, both cell lines were strongly positive for S-100 protein. The transplanted NMS-2 and NMS-2PC tumours showed the same histological features typical of MPNST. Chromosomal analysis revealed that only the NMS-2 cells had a t (1;2) chromosomal translocation. Chemosensitivity tests demonstrated that NMS-2PC cells were far more sensitive than NMS-2 cells to Adriamycin and etoposide, which had been used clinically. All-trans-retinoic acid induced a morphological change in NMS-2PC cells so that they were no longer fibroblast-like, but epithelioid cells. We believe the epitheloid components in the MPNST were derived from typical spindle cells.     

The Australian brushtail possum (Trichosurus vulpecula) gonadotrophin alpha-subunit: analysis of cDNA sequence and pattern of expression

Substantial evidence has accumulated to suggest that in the near future implementation of the veto-cell-suppressor concept in the treatment of kidney allograft recipients might lead to the establishment of life-long specific allograft tolerance in the absence of further immunosuppressive therapy. Veto suppression prevents the generation of antigen-specific T-helper and cytotoxic T lymphocytes in vitro provided that the T-lymphocyte precursors specifically recognize antigenic peptides associated with the major histocompatibility complex molecules class II and class I, respectively, expressed on the surface of the veto-active cell. Data from a large number of experimental and clinical studies strongly indicate that veto-active cells function in vivo and are capable of preventing allograft rejection. Thus, donor-cell-mediated veto activity is the most likely explanation for the well-known graft tolerizing effect of pretransplant donor blood transfusions in kidney graft recipients. A prerequisite for a veto-active environment in vivo is the establishment of lymphoid microchimerism, in which veto-active donor and recipient cells mutually downregulate potential alloaggression.     

Voiding dysfunction in human immunodeficiency virus infections

PURPOSE: We prospectively evaluated the current spectrum of urodynamic pathology in patients infected with human immunodeficiency virus (HIV) who presented with voiding dysfunction. MATERIALS AND METHODS: We obtained a directed genitourinary and neurological history, and performed a physical examination and urodynamic testing in 18 patients. A 4-channel membrane urethral catheter was used to record intravesical and intraurethral pressures simultaneously. RESULTS: Detrusor hyperreflexia was present in 28% of our patients and detrusor-sphincter dyssynergia in 28%. Detrusor areflexia, previously described as the most frequent abnormality, was uncommon in our series (6% of patients). CONCLUSIONS: This changing proportion of urodynamic diagnoses may reflect a changing pattern of neurological manifestations of HIV infection due to more aggressive management. Urodynamic evaluation remains critical for precise diagnosis and treatment in patients with HIV who present with urinary symptoms.