Failure of enflurane and halothane anesthesia to inhibit lymphocyte transformation in volunteers

Changes in the peripheral blood leukocyte count and in the ability of lymphocytes to transform in response to phytohemagglutinin were studied in healthy volunteers undergoing prolonged enflurane or halothane anesthesia without coincident surgical operation. Anesthesia was associated with a modest leukocytosis that persisted into the first post-anesthesic day, primarily due to an influx of neutrophils into the circulation. There was no significant alteration, either during or following anesthesia, in the ability of the volunteers' lymphocytes to transform in response to phytohemagglutinin when compared with either preanesthetic values or unanesthetized controls. Depression of lymphocyte transformation does not appear to follow prolonged enflurane or halothane anesthesia in the absence of a surgical procedure.     

A transient precursor of the HIV-1 protease. Isolation, characterization, and kinetics of maturation

Recently, the mechanism of autoprocessing of the protease (PR) of the human immunodeficiency virus type 1 from the model polyprotein, MBP-DeltaTF-PR-DeltaPol, which contains the protease linked to short native flanking sequences (DeltaTF and DeltaPol) fused to the maltose binding protein (MBP) of Escherichia coli, was reported (Louis, J. M., Nashed, N. T., Parris, K. D., Kimmel, A. R., and Jerina, D. M. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 7970-7974). According to this mechanism, intramolecular cleavage of the N-terminal strands of the dimeric MBP-DeltaTF-PR-DeltaPol protein leads to the formation of the PR-DeltaPol intermediate, which is subsequently converted to the mature protease by cleavage of the C-terminal strands. We now report the purification and characterization of the PR-DeltaPol intermediate and the kinetics of its processing to the mature protease. Unlike the MBP-DeltaTF-PR-DeltaPol precursor, PR-DeltaPol has proteolytic activity similar to that of the mature enzyme at pH 5.0. The pH rate profile for kcat/Km is similar to that of the mature protease above pH 4.0. Although the PR-DeltaPol is more sensitive than the mature protease toward denaturing reagents, both the enzymatic activity and the intrinsic fluorescence of PR-DeltaPol are linearly dependent on the protein concentration, indicating that the protein is largely in its dimeric form above 10 nM. In contrast to the first-order kinetics observed for the proteolytic reaction at the N terminus of the protease, the proteolytic reaction at the C terminus of the protease is second order in protein concentration. These results are discussed in terms of a mechanism in which the C-terminally located DeltaPol peptide chains are cleaved intermolecularly to release the mature protease.     

Anticryptococcal activity by alveolar macrophages from rats treated with cortisone acetate during different periods of time

Recently mouse models have shown that expression of costimulatory molecules such as B7-1 on tumor cells can induce tumor-specific immunity, suggesting that tumor cells modified to express costimulatory molecules can be a potential tumor vaccine. To investigate the importance of B7-1 co-stimulation in induction of autologous tumor immunity in humans, we established a renal carcinoma cell line, RCC-1, from a tumor resection and studied the patient's antitumor immune responses in vitro. The RCC-1 cell line constitutively expressed major histocompatibility complex (MHC) class I, intercellular adhesion molecule (ICAM)-1, and leukocyte function-associated antigen (LFA)-3 molecules, and MHC class II molecules were induced by interferon-gamma (IFN-gamma) treatment in vitro. However, neither RCC-1- nor IFN-gamma-treated RCC-1 cells expressed B7-1, and both failed to induce T-cell proliferative responses in mixed lymphocyte and tumor cell reaction (MLTR) assays, suggesting that the costimulatory signals provided by cell adhesion molecules such as ICAM-1 and LFA-3 were not sufficient to elicit an antitumor immune response. However, on transfection of the human B7-1 into RCC-1, these cells were able to induce a significant T-cell proliferation in MLTR assays. This T-cell response could be blocked by anti-B7 mAb treatment of the tumor cells. RCC-1B7 cells also induced the generation of tumor-specific cytolytic T lymphocytes to the parent RCC-1 cells in vitro, with little nonspecific cytolysis of an unrelated RCC line, A498, or autologous phytohemagglutinin (PHA) blasts. This specific cytotoxicity could be abrogated by anti-CD8 mAb and complement treatment. In summary, our study indicates that B7-1-CD28 interaction plays a critical role in induction of autologous tumor-specific cytotoxic T lymphocytes (CTLs) in humans, suggesting that the costimulatory molecule transfected tumor cells could be useful in expanding tumor-specific autologous CTL in vitro for adoptive tumor immunotherapy.     

Use of interferon-2 alpha in the treatment of cryoglobulinaemic leg ulcers

We report three cases of leg ulcers complicating cryoglobulinaemia which resisted conventional therapy but responded to interferon-2 alpha. All three cases improved with the complete resolution of painful vasculitic lesions and healing of deep ulcers. The dose of interferon to produce ulcer healing was determined by individual response with escalation of the daily dose to 4.5 x 10(6) units per day required in one case. A lower dose of maintenance interferon could be used to prevent subsequent relapses of disease.     

Changes in blood chemistries following prolonged enflurane anesthesia

In an effort to identify further the structural requirements for central dopamine receptor agonists, some monohydroxyl analogs of the known agonist 5,6-dihydroxy-2-dipropylamino-1,2,3,4-tetrahydronaphthalene were synthesized. They were examined for production of emesis in dogs and stereotyped behavior in rats. The most potent was 5-hydroxy-2-dipropylamino-1,2,3,4-tetrahydronaphthalene, which was more potent than apomorphine but less so than the dihydroxyl analog. The two enantiomers of the monohydroxyl analog were synthesized by conventional methods from an optically active intermediate, 2-benzylamino-5-methoxy-1,2,3,4-tetrahydronaphthalene. The resolution of this amine was performed with the aid of mandelic acid. Dopaminergic activity was found to be confined to the levo enantiomer. Requirements for both substitution and chirality in the tetralines were found to correspond closely to those known for the dopaminergic aporphines.     

The comparison of early fluid therapy in extensive flame burns between inhalation and noninhalation injuries

Dopamine hydrochloride bearing positively charged small liposomes was prepared by sonicating the multilamellar vesicles. These vesicles were characterized for their physical attributes (shape, size, charge, drug entrapment efficiency, and drug leakage). The drug release kinetics from the liposomes were also studied and found to be Fickian-type diffusion. In vivo performance of the drug-entrapped liposomes was assessed by periodic measurement of drug- (chlorpromazine) induced catatonia in Sprague-Dowley rats. These results were compared with the plain dopamine HCl and levodopa preparations as well with the marketed formulation of levodopa containing carbidopa (Syndopa). These studies revealed that the dopamine can be effectively delivered to the brain by incorporating it into liposomes, and its degradation in circulation can also be protected. The results of liposomal formulation were found to be superior compared to plain levodopa as well as Syndopa.     

A relative localisation system of a mobile robot

This paper describes a localisation system applied to vehicle displacements on irregular grounds and at moderate speed (about 1 m/s). It is composed of a gyrometer and a Doppler sensor, which give, by integration, the attitude and position of the vehicle supporting them, without contact with the ground. The precision of the obtained localisation is about 2% for ranges of about a hundred meters.