Induction of neutralizing antibody in mice by immunization with recombinant 56 kDa protein of Orientia tsutsugamushi

Anti-oriential antibody inhibits Orientia tsutsugamushi attachment to, and penetration of, host cells. However, O. tsutsugamushi antigens that induce the production of a neutralizing antibody have not been identified. The authors immunized mice and rabbits with the recombinant 56 kDa protein of O. tsutsugamushi fused to the maltose binding protein of Escherichia coli (MBP-Bor56) and analysed their effect on O. tsutsugamushi attachment to or penetration of L929 cells. O. tsutsugamushi attachment and penetration were measured by using an indirect immunofluorescent antibody assay (IFA). O. tsutsugamushi growth in L929 cells was determined by [3H]thymidine uptake assay. By IFA, we observed a 96% reduction of attachment or penetration of O. tsutsugamushi treated with rabbit anti-MBP-Bor56 sera. [3H]thymidine uptake showed that mouse anti-MBP-Bor56 sera caused a 91% reduction in O. tsutsugamushi growth, when compared to mouse anti-MBP sera. These results suggest that the 56 kDa protein of O. tsutsugamushi plays an important role in O. tsutsugamushi attachment to or penetration of cells.     

The history of research on blood group genetics: initial discovery and diffusion

During the 1920s and 1930s the resting of blood groups for large numbers of people became a very common practice. Although much of this was to ensure compatibility for blood transfusion, over 1,000 articles were published with results of tests on over 1.3 million people to answer more theoretical, scientific questions. The motivation for much of this research was the possible link between the well established hereditary blood types and other possible inherited traits. Because the existence of the blood groups was a rather sudden discovery, the record of this publication offers an excellent case study of the diffusion of new scientific knowledge. Differences in the beginning of blood group research from country to country reveal some important influences of social setting on the spread and application of the new discoveries.     

Testicular plasmacytoma following chemical orchiectomy: potential role of hypogonadism in myeloma proliferation

We present a case of a 55 year old man with multiple myeloma who underwent autologous stem cell transplantation and subsequently developed testicular myeloma. Testicular enlargement was observed only after treatment of an incidental prostatic adenocarcinoma with chemical orchidectomy at a time when myeloma was controlled systemically. A subsequent bilateral surgical orchiectomy revealed plasmacytoma in both testis. Enhanced production of B-lymphocytes after castration has been reported and implicates testosterone as a possible negative regulator of B-cell production. We propose that the androgen deficient state may have contributed to the development of plasmacytoma of the testes in our patient. The regulatory role of sex steroids in B-cell development is discussed.     

Efficacy of clindamycin hydrochloride capsules for the treatment of deep pyoderma due to Staphylococcus intermedius infection in dogs

Clindamycin hydrochloride capsules (11 mg/kg body weight, q24 h) were administered orally to 20 dogs with deep staphylococcal pyoderma. Response to therapy was excellent in 100% of the dogs. Duration of therapy varied from 21 to 91 d, with an average duration of 45 d. Relapses occurred in 25% of the dogs within a 3-month period. One dog vomited when the clindamycin was given on an empty stomach. Under the conditions of the study, clindamycin was an effective, safe, and convenient antibiotic for the treatment of deep staphylococcal pyoderma in dogs.     

Application of transcranial Doppler sonography to evaluate cerebral hemodynamics in carotid artery disease. Comparative analysis of different hemodynamic variables

BACKGROUND AND PURPOSE: Transcranial Doppler sonography in combination with manipulation of cerebral resistance vessels is widely used to screen patients with suspected intracranial hemodynamic disturbances. Maximal flow velocity (Vmax), mean flow velocity (Vmean), cerebral pulsatility index (CPi), and cerebral resistance index (CRi) have all been used to describe cerebral hemodynamics. The present study examined CO2 reactivity of the above hemodynamic variables with respect to its variability between different age groups and its capability to discriminate between normal and abnormal findings. METHODS: Absolute and relative CO2 reactivity of Vmax, Vmean, CRi, and CPi were determined in both hemispheres in 30 young and 37 elderly control subjects and in 245 consecutive patients with strictly unilateral symptomatic (n = 101) or asymptomatic (n = 144) carotid artery disease (> 80% stenosis or occlusion). RESULTS: Hemispheric reactivities of Vmean, CRi, and CPi were significantly age dependent. Hemispheric Vmax reactivity and interhemispheric differences of individual reactivities (except absolute CPi reactivity) did not vary with age and could therefore be used to define normal values. Patient classification according to these values revealed different frequencies of subjects with pathological findings (3% for hemispheric Vmax reactivity, 5% to 7% for interhemispheric differences of Vmax or Vmean reactivity, 39% and 45% for interhemispheric differences of relative CRi and CPi reactivity, respectively). CONCLUSIONS: Hemispheric reactivities are less suitable to evaluate cerebral hemodynamics than interhemispheric differences, since most of the latter do not vary with age. However, interhemispheric differences vary with respect to their discriminatory power. Power is low for interhemispheric differences of Vmax and Vmean reactivity, since the corresponding frequencies of abnormal findings do not differ from the 5% frequency expected in the reference population (reference range defined as mean +/- 2 SD). With respect to the discriminatory power, interhemispheric differences of relative CRi and CPi reactivity may be superior to other parameters.     

Polysomnographic sleep measures in patients with uremic and idiopathic restless legs syndrome

In the present study, the nocturnal electroencephalographic sleep pattern, the number of periodic leg movements (PLM) during sleep and wakefulness, and the subjective sleep parameters of patients with uremic (n = 10) and idiopathic (n = 17) restless legs syndrome (RLS) were compared. The main finding was that the total number of PLM (p = 0.019), the PLM index (p = 0.018), and the PLM index while awake (p = 0.003) were significantly higher in patients with uremic RLS compared with patients who had idiopathic RLS. Additionally, both groups showed a distinct time-of-night pattern of PLM activity. Polysomnographic measures of sleep continuity (total sleep time, sleep efficiency, sleep onset latency, time awake) and sleep architecture (amount of nonrapid eye movement sleep stages 1, 2, 3, and 4 and the amount of rapid eye movement sleep) did not differ between uremic and idiopathic RLS patients. With regard to subjective parameters, sleep quality was estimated to be worse in uremic RLS (p = 0.033), whereas other parameters (for example, severity of RLS, quality of life) did not differ between the two groups. It is suggested that uremia itself worsens the motor symptoms of RLS, probably as a result of increased excitability.     

Identification of six novel autophosphorylation sites on fibroblast growth factor receptor 1 and elucidation of their importance in receptor activation and signal transduction

Fibroblast growth factor receptor (FGFR) activation leads to receptor autophosphorylation and increased tyrosine phosphorylation of several intra cellular proteins. We have previously shown that autophosphorylated tyrosine 766 in FGFR1 serves as a binding site for one of the SH2 domains of phospholipase Cy and couples FGFR1 to phosphatidylinositol hydrolysis in several cell types. In this report, we describe the identification of six additional autophosphorylation sites (Y-463, Y-583, Y-585, Y-653, Y-654 and Y-730) on FGFR1. We demonstrate that autophosphorylation on tyrosines 653 and 654 is important for activation of tyrosine kinase activity of FGFR1 and is therefore essential for FGFR1-mediated biological responses. In contrast, autophosphorylation of the remaining four tyrosines is dispensable for FGFR1-mediated mitogen-activated protein kinase activation and mitogenic signaling in L-6 cells as well as neuronal differentiation of PC12 cells. Interestingly, both the wild-type and a mutant FGFR1 (FGFR1-4F) are able to phosphorylate Shc and an unidentified Grb2-associated phosphoprotein of 90 kDa (pp90). Binding of the Grb2/Sos complex to phosphorylated Shc and pp90 may therefore be the key link between FGFR1 and the Ras signaling pathway, mito-genesis, and neuronal differentiation.