The spatial distribution of the antagonistic surround of MT/V5 neurons

The majority (217/325, 66%) of the neurons in the middle temporal (MT) area/V5 show strong antagonistic surrounds, defined here by a decrease of at least 50% in the summation curve. We mapped the antagonistic surround in 145 such cells, using eight circularly distributed surround stimulus patches (Surround Asymmetry Test, SAT) and also mapped the surround in 51 of these 145 cells using a grid consisting of 25 square patches (Surround Mapping Test, SMT). Both tests showed that the angular surround distribution was non-uniform in the majority of these neurons. In half the neurons, the antagonistic surround was asymmetric, and arose from a single region on one side of the excitatory receptive field (ERF). In another quarter of the sample the surround was bilaterally symmetric, and arose from a pair of regions on opposite sides of the ERF. Only the remaining 20% showed a circularly symmetric surround distribution. These three groups differed in their laminar distribution. The SMT showed that, radially, the surround antagonism reached a maximum, on average, at 1.5 times the ERF radius. Detailed comparisons of the spatial relationships of excitatory and inhibitory regions of the RF components shows that non-homogeneity of the surround influence appears to be an intrinsic property of the surround. Such a property may underly the extraction of the surface orientation and curvature from speed patterns.      

Evaluation of Suspected Monoclonal Gammopathies: Experience in a Tertiary Care Hospital

Background

Monoclonal gammopathies occurs in patients with malignant diseases of plasma cells and lymphocytes and in few benign conditions. The objective of this study was to assess the precision, accuracy and confirmation of monoclonal gammopathies on serum protein electrophoresis (SPE) and the clinical relevance of detection and characterization of M component.

Methods

All samples received for serum electrophoresis in the last 3 years were analysed for data on M band positivity and correlating it with clinical profile of the patients. Immunofixation (IFE), Immunoelectrophoresis (IEP) and IgG, IgM estimation were carried out in few cases. The follow up of cases was done by serial monitoring of SPE and β₂ microglobulin levels.

Results

1155 samples were received during the 3 years period. 282 (24.4%) samples were positive for M component on SPE. Of these, 239 (84.8%) patients had M spike in λ region and 43 patients had M spike in β region. The mean load of the M protein band in the λ region was 37.8% and in β region was 35.8%. IgG with κ chain was seen in 40%, IgG with λ chain was seen in 50%, 5% patients each had IgM with κ and IgA with λ light chain. 246 samples (96.5%) had high levels of β₂ microglobulin. Of the 116 cases of multiple myeloma, IgG levels was more commonly raised (5%) as compared to IgA (6.9%) and IgM (5.2%).

Conclusion

It is recommended that SPE should be performed in patients having unexplained weakness, anaemia, back pain, osteoporosis, osteolytic lesions, fractures, renal insufficiency or recurrent infections.Key Words: Serum protein, Electrophoresis, M band, Multiple myeloma     

Plasmodium vivax: a cause of malnutrition in young children

We studied the aetiology of malnutrition in a cohort of 1511 children < 10 years old in Espiritu Santo, Vanuatu. Malnutrition was categorized using standard anthropometric criteria as: underweight [weight-for-age (WA) Z score < -2], wasting [weight-for-height (WH) Z < -2], or stunting [height-for-age (HA) Z < -2]. On multiple logistic regression analysis, the only factors significantly associated with wasting were age < 5 years [OR (95% CI) 1.8 (1.2-2.9), p = 0.01] and having suffered one or more episodes of clinical P. vivax malaria in the 6 months preceding nutritional assessment [OR 2.4 (1.3-4.4), p = 0.006]. The incidence of P. vivax infection was significantly higher during the 6 months preceding assessment in underweight vs. non-underweight children [incidence rate ratio (IRR) 2.6 (1.5-4.4), p < or = 0.0001). These groups had similar incidences of clinical P. falciparum infection during the same period [IRR 1.1 (0.57-2.1) p = 0.8] and of either species during the 6 months following assessment [IRR P. vivax 1.3 (0.9- 2.0) p = 0.2; IRR P. falciparum 1.3 (0.9-1.9) p = 0.2]. In these children, P. vivax malaria was a major predictor of acute malnutrition; P. falciparum was not. Wasting neither predisposed to nor protected against malaria of either species. Although P. vivax malaria is generally regarded as benign, it may produce considerable global mortality through malnutrition.      

Elevated levels of RDW is associated with non-valvular atrial fibrillation

Red cell distribution width (RDW) and neutrophil/lymphocyte ratio (NLR) have been found to be associated with cardiovascular diseases. Only a few trials have investigated the correlation of these parameters with postoperative atrial fibrillation (AF). However, the correlation of these parameters in non-valvular AF is still unclear. We retrospectively analyzed consecutive AF patients from medical records and included 117 non-valvular AF patients (103 paroxysmal and 14 chronic AF). All subjects underwent physical examination and echocardiographic imaging. Complete blood counts (CBCs) were analyzed for hemoglobin, RDW, neutrophil and lymphocyte counts as well as mean corpuscular volume. Results of CBC tests within the previous year were also included and the averages were used. The demographic and echocardiographic properties of non-valvular AF group were comparable to the control group except for left atrial volumes which were increased in AF (median 33.1, IQR 26.3–41.1 cm³ vs. median 26.4, IQR 24.2–28.9 cm³; p = 0.01). RDW levels were significantly higher in the AF group (median 13.4 %, IQR 12.9–14.1 %) compared to the control (median 12.6 %, IQR 12.0–13.1 %; p = 0.01). NLR was not statistically different in the AF group and the controls (2.04 ± 0.94 vs. 1.93 ± 0.64, respectively; p = 0.32). Hs-CRP levels were higher in the AF group compared to the controls (median 0.84, IQR 0.30–1.43 mg/L vs. median 0.29, IQR 0.18–0.50 mg/L, respectively; p = 0.01). Multivariate logistic regression analysis revealed RDW (OR 4.18, 95 % CI 2.15–8.15; p = 0.01), hs-CRP (OR 3.76, 95 % CI 1.43–9.89; p = 0.01) and left atrial volume (OR 1.31, 95 % CI 1.06–1.21; p = 0.01) as the independent markers of non-valvular AF. Multivariate linear regression analysis revealed that hemoglobin levels (standardized β coefficient = ?0.252; p = 0.01) and the presence of AF (standardized β coefficient = 0.336; p = 0.01) were the independent correlates of RDW levels. Elevated RDW levels, not NLR, may be an independent risk marker for non-valvular AF.     

Differential effect of phorbol esters and interleukin-3 on protein kinase C isoform content and kinase activity in the FDC-P1 cell line

FD/PMA is a subclone of the interleukin-3 (IL-3)-dependent, FDC-P1 cell line, which proliferates in response to either 12-O- tetradecanoylphorbol-13 acetate (PMA) or IL-3. While several endogenous substrates were phosphorylated in response to protein kinase C (PKC) activation in FDC-P1, phospholipid-dependent phosphorylation in the FD/PMA grown in PMA was not observed. Basal, phosphatidylserine- independent, and diolein-independent phosphorylation of cytosolic substrates with molecular weights of 17, 52, 57, and 105 Kd were enhanced in FD/PMA cells grown in PMA as compared with FDC-P1 cells cultured in IL-3. Phosphorylation of a 105-Kd substrate was enhanced in the particulate fraction of FD/PMA cells maintained in PMA. The 17-Kd substrate in FD/PMA cells comigrated with a substrate phosphorylated in a PKC-dependent manner in FDC-P1 cells. Phosphorylation of the 52- and 57-Kd substrates, but not of the 17-Kd substrate, was inhibited by H-7 and staurosporine. A portion of the PMA-induced cytosolic kinase activity coeluted with PKC on diethyl aminoethyl chromatography. While FD/PMA cells cultured in PMA contained negligible PKC-dependent phosphorylation of endogenous substrates or histone, alpha and epsilon PKC isoforms were detected by Western blot analysis. PKC phosphotransferase activity was observed in FD/PMA cells grown in PMA when peptides corresponding to residues 720 to 737 of PKC-epsilon or residues 4 to 14 of myelin basic protein were used as substrates. These data indicate that maintenance of FD/PMA cells in PMA stimulates proliferation and markedly alters PKC substrate specificity. Generation of at least two phospholipid-independent kinases occurs in PMA-treated cells.     

Correlation of drug sensitivity in vitro with clinical responses in childhood acute myeloid leukemia

Clonogenic cells from 41 children with newly diagnosed acute myeloid leukemia (AML) were tested in vitro for their sensitivity to cytarabine (Ara-C) and daunorubicin (DNR). The findings were then compared with the patients' responses to induction chemotherapy that uniformly included Ara-C and DNR. Light-density marrow cells were incubated with either or both drugs for one hour and cultured over leukocyte feeder layers; clusters and colonies were scored on days 7, 10, and 14. Only the percentage of cell kill in the presence of 1.8 mumol/L DNR was significantly associated with responses to induction therapy: median of 45% (range, 0% to 98%) for patients achieving complete remission v 16% (range, 4% to 23%) for nonresponders (P = .007). The relationship between clonogenic cell kill less than or equal to 23% and clinical responses was striking. Of the 11 evaluable patients with in vitro findings in this category, ten either failed induction therapy or relapsed within 1 year after attaining remission. Kaplan-Meier analysis of relapse-free survival times indicated longer durations of remission for patients whose blast cells showed increased sensitivity in vitro to Ara-C alone, DNR alone, or a combination of the two agents. Seven of 11 patients with cell kills of greater than or equal to 49% in the presence of 1.25 mumol/L Ara-C remain free of leukemia, compared with only one of 12 whose cells were less sensitive to the drug (P = .006). We conclude that the in vitro sensitivity of clonogenic leukemic progenitors to DNR and Ara-C correlates with treatment outcome in children with newly diagnosed AML.     

Thrombospondin mediates the cytoadherence of Plasmodium falciparum- infected red cells to vascular endothelium in shear flow conditions

Cerebral malaria is thought to involve specific attachment of Plasmodium falciparum-infected knobby red cells to venular endothelium. The nature of surface ligands on host endothelial cells that may mediate cytoadherence is poorly understood. We have investigated the effects of soluble thrombospondin, rabbit antiserum raised against thrombospondin, and human immune serum on cytoadherence of parasitized erythrocytes in ex vivo mesocecum vasculature. Preincubation of infected red cells with soluble thrombospondin or human immune serum inhibits binding of infected red cells to rat venular endothelium. Infusion of the microcirculatory preparation with rabbit antithrombospondin antibodies before perfusion of parasitized erythrocytes also resulted in decreased cytoadherence. In addition, incubation of infected cells with human immune sera obtained from malaria patients significantly inhibited the observed cytoadherence. Our results indicate that thrombospondin mediates binding of infected red cells to venular endothelium and may thus be involved in the pathogenesis of cerebral malaria.