Pallidotomy in Parkinson's disease improves single-joint, repetitive, ballistic movements, but fails to modify multijoint, repetitive, gestural movements.

We studied 12 non-demented PD patients in on state before and 3 months after posteroventral pallidotomy (PVP), in order to evaluate the effects of surgery upon an unconstrained, multijoint skilled movement as well as a single joint, repetitive, ballistic movement. A Selspot II System was used for three-dimensional data acquisition, processing and reconstruction of limb trajectories. Specific wrist kinematic features of spatial accuracy (linearity and planarity), temporal attributes (acceleration and velocity), spatiotemporal relationships (velocity-curvature coupling), and joint kinematic variables (relationships between wrist and elbow velocities and relative arm angle amplitudes) for each cycle of movement were graphically and numerically analysed. QMC was applied to single joint, repetitive, ballistic movements. QMC significantly improved after PVP (P < 0.0006). However, wrist as well as joint kinematic variables of the gestural movements failed to change significantly after PVP. The lack of improvement of the kinematic abnormalities of the gestural movement in PD patients would indicate that they are unrelated to the basic motor deficit; most likely they are the result of a disruption of a complex of sensorimotor integration processes due to abnormal parieto-frontal basal ganglia interaction.     

Cyclic guanosine 3'3' monophosphate concentrations in pre-eclampsia: effects of hydralazine

Objective To elucidate the role of the L-arginine: nitric oxide pathway in pregnancy and pre-eclampsia.
Participants Pregnant women (nulliparous, age < 25 years). Normotensive pregnancy (   n = 22  ) was defined when blood pressure remained at levels of < 120/80 mmHg and there was no proteinuria. Women with pre-eclampsia (   n = 22  ) had blood pressure measurements of > 140/90 mmHg and proteinuria of > 300 mg/l. Nonpregnant normotensive women (   n = 22  ) were studied as controls.
Study Design Blood samples were taken for measurements of ionised calcium, atrial natriuretic factor, cyclic guanosine 3'5'monophophate (GMP), arginine and asymmetric dimethylarginine. Urine samples were collected for determination of cyclic GMP excretion. Cyclic GMP concentrations were also determined in 12 women with severe pre-eclampsia before and after treatment with hydralazine.
Results L-arginine, asymmetric dimethylarginine and atrial natriuretic factor were not different in any group. Cyclic GMP concentrations in plasma [0.94 (SD 0.23) nM] as well as in urine [50.1 (SD15.7)μM] were increased significantly (   P < 0.05  ) in normal pregnancy compared to nonpregnant controls [plasma mean 0.46 (SD 0.12) nM and urine mean 18.4 (SD 10.3) μM], but not in the pre-eclampsia group [plasma mean 0.48 (SD 0.10) nM and urine mean 24.1 (SD 14.5) μM]. Concentrations of cyclic GMP in plasma and urine increased significantly (   P < 0.05  ) in women treated with hydralazine.
Conclusions The differences in cyclic GMP concentrations may reflect differences in nitric oxide production. Hydralazine increases cyclic GMP concentrations in severely pre-eclamptic women. This action could explain the antihypertensive effect of hydralazine.     

Interaction of Nucleoside Analogues with the Sodium–Nucleoside Transport System in Brush Border Membrane Vesicles from Human Kidney

The therapeutic efficacy of nucleosides and nucleoside analogues as antitumor, antiviral, antiparasitic, and antiarrhythmic agents has been well documented. Pharmacokinetic studies suggest that many of these compounds are actively transported in the kidney. The goal of this study was to determine if therapeutically relevant nucleosides or analogues interact with the recently characterized Na⁺-driven nucleoside transport system of the brush border membrane of the human kidney. Brush border membrane vesicles (BBMV) were prepared from human kidney by divalent cation precipitation and differential centrifugation. The initial Na⁺-driven ³H-uridine uptake into vesicles was determined by rapid filtration. The effect of several naturally occurring nucleosides (cytidine, thymidine, adenosine), a pyrimidine base (uracil), a nucleotide (UMP), and several synthetic nucleoside analogues [zidovudine (AZT), cytarabine (Ara-C), and dideoxycytidine (ddC)] on Na⁺–uridine transport was determined. At a concentration of 100 µM the naturally occurring nucleosides, uracil, and UMP significantly inhibited Na+-uridine transport, whereas the three synthetic nucleoside analogues did not. Adenosine competitively inhibited Na+-uridine uptake with a K _i of 26.4 µM (determined by constructing a Dixon plot). These data suggest that naturally occurring nucleosides are substrates of the Na⁺–nucleoside transport system in the renal brush border membrane, whereas synthetic nucleoside analogues with modifications on the ribose ring are not. The K _i of adenosine is higher than clinically observed concentrations and suggests that the system may play a physiologic role in the disposition of this nucleoside.     

Expression of CD83 in the murine immune system

CD83 is used as a marker for mature dendritic cells (DC) in man. We have developed a new monoclonal antibody (mAb), Michel-17, that specifically recognizes mouse CD83. We show that murine CD83 is expressed mainly on mature DC and on activated T cells. Histological analysis of serial spleen sections revealed a CD83 expression pattern resembling that of MIDC-8, a known murine DC marker molecule. In contrast to other costimulatory receptors, cross-linking of CD83 with the mAb Michel-17 on DC or T cells does not induce any activation signals. Our data describe for the first time the expression pattern of murine CD83, which is comparable to that of human CD83.The unique mAb Michel-17 will help to elucidate the biological functions of the CD83 molecule in more detail.     

Vaccine development strategies for improving immunization: the role of modern immunology

An ideal vaccine has certain biological and physical characteristics. Technological advances have provided new strategies that may help the design of such a vaccine.     

Detection of Rickettsia felis in a New World flea species, Anomiopsyllus nudata (Siphonaptera: Ctenophthalmidae)

The flea and rodent samples studied in this project were collected from field study sites in New Mexico from winter 1998 to spring 2001. During this period, 155 small rodents (14 different species) were live-trapped and combed for the presence of fleas. A total of 253 fleas were collected, comprising 21 species. Two of the 253 fleas collected were polymerase chain reaction (PCR) positive for the Rickettsia 17-kDa protein gene. These two fleas were both Anomiopsyllus nudata Baker, each collected from an individual Neotoma albigula Hartley, on two occasions. Individual fleas positive for the Rickettsia 17-kDa protein gene were then tested with primers targeting the rickettsial genes for citrate synthase (gltA) and two major outer membrane proteins (ompA and ompB). The nucleotide sequences of the PCR products of these two fleas were identical to each other and were 100% (394/394), 100% (1150/1150), 99.8% (469/470), and 99.3% (818/824) similar to the corresponding sequences of the 17-kDa, gltA, ompA, and ompB genes of Rickettsia felis, respectively. Flea homogenates of individual PCR-positive fleas were inoculated into shell vials seeded with Vero cells, and the Gimenez stain technique was used to demonstrate the presence of Rickettsia-like organisms in detached cells found in aspirated medium 19 d after inoculation. These cells were harvested and tested by PCR, targeting portions of the 17-kDa and gltA genes, resulting in products 100% identical to R. felis. This work comprises the first report of R. felis detection in a flea species (A. nudata) endemic to the New World.     

Correlation between Presence of Viable Bacteria and Presence of Endotoxin in Middle-Ear Effusions

The presence of endotoxin (detected by the Limulus amebocyte lysate assay) was compared to the presence of viable Haemophilus influenzae and Moraxella catarrhalis (detected by PCR) in 106 middle-ear effusions from pediatric patients with chronic otitis media. Endotoxin was found in 81 of the 106 specimens. Of these 81 specimens, 66 (81.5%) also tested positive for one or both of the gram-negative bacteria H. influenzae and M. catarrhalis. The data suggest that viable gram-negative bacteria, detectable by PCR but often undetectable by culture, may be the source of endotoxin in middle-ear effusions.     

Development and comparison of enzyme immunoassays for diagnosis of Chagas' disease using fixed forms of Trypanosoma cruzi (Epimastigotes, Amastigotes, and Trypomastigotes) and assessment of antigen stability for the three assays

Three enzyme immunoassays (EIAs) for diagnosis of Chagas' disease were developed with fixed forms of Trypanosoma cruzi using a panel of 435 sera from the following groups: Venezuelan subjects positive by immunofluorescence (n = 70), Venezuelan healthy controls (n = 85), healthy Canadians (n = 166), and subjects with other parasitic diseases (n = 114). All assays achieved 100% sensitivity and reasonable specificity for amastigotes (97.6%), epimastigotes (98.3%), and trypomastigotes (99.3%). The fixed-trypomastigote assay was stable over 4 months at 4 degrees C and room temperature. These data suggest that a fixed-trypomastigote EIA may be a suitable candidate for blood bank screening.