Novel NMDA antagonists: replacement of the pyridinium ring of 6,11-ethanobenzo[b]quinolizinium cations with heteroisoquinolinium cations

Replacement of the pyridinium ring of 6,11-ethanobenzo[b]quinolizinium cations with thiazolium (4a and 4b) and N-methylimidazolium (4c and 4d) resulted in equipotent compounds in the [3H]TCP binding assay. The corresponding N-methyl-1,2,4-triazolium analogs were less potent in this assay. The thiazolium derivative 4b, with a Ki = 2.9 nM, is being evaluated as a possible neuroprotective N-methyl-D-aspartic acid (NMDA) antagonist.     

Minimum effort factor approach for sensor-based control of a four-joint 6-dof redundant manipulator

A sensor-driven control model and a minimum effort control algorithm in terms of time and energy expended during the execution of a movement strategy are described and validated for a multijointed cooperating robotic manipulator. Considering smooth, human-like (anthropomorphic) movements, using joint motion profiles achievable in real time as well as sensory information from all joints, and evaluating the total work expended by each manipulator joint during the execution of a movement strategy, a minimum effort motion trajectory is synthesized to precisely and efficiently position the robotic arm end-effector. This sensor-based approach significantly reduces the computational requirements for such cooperative motion. The minimum effort control algorithm generates several human-like arm movement strategies and selects the best strategy on the basis of expendable effort. The algorithm has an inherent basis to deal with obstacles in an efficient way. Detailed examples are described from the simulation studies. © 1994 John Wiley & Sons, Inc.     

Evidence for superantigen involvement in insulin-dependent diabetes mellitus aetiology

Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease whose onset is believed to be triggered by unknown environmental factors acting on a predisposing genetic background. Islet-infiltrating T (IIT) cells from two IDDM patients, who had died at the onset of the disease from brain swelling as a complication of ketoacidosis, were analysed. The results provided evidence for the involvement of a pancreatic islet cell membrane-bound superantigen as a diabetes aetiopathogenetic factor. There was a selective expansion of a T-cell receptor (TCR) variable segment of the beta-chain (V beta 7) in these IIT cells in association with unselected V alpha-chain segments; extensive junctional diversity of the TCR V beta 7 chains; and evidence of positive selection, after exposure to diabetic islet cell membrane preparations, of V beta 7+ T-cell clones among peripheral blood lymphocytes from non-diabetic individuals.     

Ventilatory response to severe acute hypoxia in guinea-pigs and rats with high hemoglobin-oxygen affinity induced by cyanate

Laparoscopic pelvic lymph node dissection has been applied as a minimally invasive staging technique for men with prostate cancer. This procedure has been shown to shorten markedly postoperative hospitalization, decrease analgesic requirements and shorten convalescence period compared to open pelvic node dissection. However, the laparoscopic procedure takes longer to perform and many disposable instruments are used, thus increasing the cost. We determine the overall cost of laparoscopic versus open pelvic lymph node dissection. Between January 1989 and April 1992, 61 men underwent only staging pelvic lymph node dissection for cancer of the prostate at a single university teaching hospital. Of these patients 11 and 50 underwent open and laparoscopic pelvic lymph node dissection, respectively. Information from the hospital business office was reorganized into preoperative, intraoperative and postoperative expenses. All individual charges were transformed up or down to the dollar amounts of the 1990 to 1991 fiscal year so as to correct for inflationary changes. Preoperative costs were not significantly different between the 2 operative approaches. Intraoperative expenses were 52% greater if laparoscopic pelvic lymph node dissection was performed and can be explained by the longer operative times and use of disposable instrumentation. However, the postoperative period lasted an average of 1.61 days following laparoscopic pelvic lymph node dissection. Postoperative nursing and analgesic requirements were significantly more for patients undergoing open pelvic lymph node dissection. The overall postoperative costs following open pelvic lymph node dissection were 280% more expensive than for the laparoscopic procedure. The overall total costs were approximately $1,250 more for laparoscopic pelvic lymph node dissection. Wages lost or earned during this period and rapid return to normal activity following laparoscopic pelvic lymph node dissection would, in our opinion, justify this additional cost.     

Enrichment of macaroni with cellulose-derivative protein complex from whey and corn steep liquor

Macaroni was prepared from semolina fortified with 3, 6 and 9% CMC-protein (CMC — carboxymethyl cellulose) or HEC-protein (HEC — hydroxyethyl cellulose) complexes from whey and corn steep liquor to increase the protein quality and quantity. Fortification increased the protein content up to 14.2% in DM (vs. 12.1% in control) for macaroni. Water absorption, dough weakening and mixing tolerance index were decreased, while dough development time and dough stability were increased when the amount of precipitated cellulose-protein complex from whey and corn steep liquor in the blends increased. Addition of both tested cellulose-protein complexes improved cooking quality by increasing the weight and volume of cooked macaroni, but cooking losses were greater. Sensory evaluation of the colour, flavour and appearance of macaroni were improved as a result of adding cellulose-protein complex from whey. Macaroni samples prepared from dough mixtures with 6 and 9% of cellulose-protein complex from corn steep liquor were less acceptable than those prepared from 100% semolina.     

A non-specific lipid transfer protein from Arabidopsis is a cell wall protein

Lipid transfer proteins (LTPs), mediate the transfer of phospholipids between membranes in vitro. However, the in vivo function of LTPs is not known. To determine the precise location of a non-specific LTP from Arabidopsis, a cDNA clone was used to produce an Arabidopsis LTP:protein A fusion. Antibodies raised against the fusion were used to localize the Arabidopsis LTP by immunoelectron microscopy. LTP was found to be located in the cell wall, mainly in epidermal cells. This location appears to be inconsistent with the proposed role of the protein in intracellular lipid transfer.     

Cooperation of Ito cells and hepatocytes in the deposition of an extracellular matrix in vitro

Cellular and molecular mechanisms involved in the deposition of extracellular matrix components in both normal and fibrotic liver are still poorly understood. We have investigated the influence of cooperation between Ito cells and hepatocytes in matrix deposition in vitro. Immunoprecipitation of radiolabeled proteins from media of 5-day-old Ito cell primary cultures showed that these cells secreted high levels of the major basement membrane components, ie, collagen IV, laminin, and entactin/nidogen. By immunocytochemistry, precursors of basement membrane components were found intracellularly, but only scarce deposits were seen around the cells. When hepatocytes were added to 2-day-old Ito cell primary cultures, they established close contacts with Ito cells in less than 24 hours and expressed ZO-1, a tight junction-associated protein not detectable in standard hepatocyte culture. Cytochemistry analysis revealed an abundant extracellular matrix deposited over hepatocyte cords and between hepatocytes and Ito cells. Immunocytochemistry studies showed that this matrix contained laminin, fibronectin, and collagens proIII and IV. These data indicate that a high level of matrix protein synthesis by liver cells in vitro is not sufficient to induce extracellular matrix deposition, and that cell-cell interactions are strongly involved in this process. Hepatocyte/Ito cell co-culture, which may reflect the actual situation in vivo, represents a useful tool for studying liver fibrogenesis.