Haemonchus contortus glycoproteins contain N-linked oligosaccharides with novel highly fucosylated core structures

Structural studies on the N-linked oligosaccharides of Haemonchus contortus, an economically important nematode that parasitizes domestic ruminants, have revealed core fucosylation of a type not previously observed in any eukaryotic glycoprotein. Mass spectrometric analyses were performed on detergent extracts of homogenized adult H. contortus and on purified H11, a glycoprotein isolated from intestinal brush borders which has been previously shown to be an effective vaccine antigen. The major N-linked glycans identified in the present study have up to three fucose residues attached to their chitobiose cores. The fucoses are found at the 3- and/or 6-positions of the proximal GlcNAc and at the 3-position of the distal GlcNAc. The latter substitution is unique in N-glycans. Most anti-H11 monoclonal antibodies are known to recognize carbohydrate epitopes, and it is possible that the newly discovered multifucosylated core structures are highly immunogenic in this glycoprotein.     

Memory-enhancing effects of secreted forms of the beta-amyloid precursor protein in normal and amnestic mice

When administered intracerebroventricularly to mice performing various learning tasks involving either short-term or long-term memory, secreted forms of the beta-amyloid precursor protein (APPs751 and APPs695) have potent memory-enhancing effects and block learning deficits induced by scopolamine. The memory-enhancing effects of APPs were observed over a wide range of extremely low doses (0.05-5,000 pg intracerebroventricularly), blocked by anti-APPs antisera, and observed when APPs was administered either after the first training session in a visual discrimination or a lever-press learning task or before the acquisition trial in an object recognition task. APPs had no effect on motor performance or exploratory activity. APPs695 and APPs751 were equally effective in the object recognition task, suggesting that the memory-enhancing effect of APPs does not require the Kunitz protease inhibitor domain. These data suggest an important role for APPss on memory processes.     

Reverse adaptation studied by recording short-latency auditory evoked potentials

Difficulties of diagnosis of pleural neoplasms in biopsies are discussed. The short history of serous tumors as entity, their classification, methodological approaches to their morphological diagnosis are outlined. It is concluded that the problem of neoplastic pleural diseases verification can be solved by clinical and morphological correlations. Histochemistry, immunomorphology, and electron microscopy should be combined with conventional morphologic methods used in biopsy investigations.     

A naturally occurring mutation in Fc gamma RIIA: a Q to K127 change confers unique IgG binding properties to the R131 allelic form of the receptor

Fc gamma RIIa is widely expressed on hematopoietic cells. There are two known allelic polymorphic forms of Fc gamma RIIa, Fc gamma RIIa-R131 and Fc gamma RIIa-H131, which differ in the amino acid at position 131 in the second lg-like domain. In contrast to Fc gamma RIIa-R131, Fc gamma RIIa-H131 binds hlgG2 but not mIgG1, and this differential binding has clinical implications for host defense, autoimmune disease, immunohematologic disease, and response to therapeutic monoclonal antibodies. We identified a novel Fc gamma RIIA genotype in a healthy individual homozygous for Fc gamma RIIA R/R131 in whom a C to A substitution at codon 127 changes glutamine (Q) to lysine (K) in one of the two Fc gamma RIIA genes. This individual's homozygosity for Fc gamma RIIA-R/R131 leads to the prediction that the receptors on her cells would not bind hIgG2. Monocyte and neutrophil phagocytosis of hIgG2-opsonized erythrocytes was significantly higher (P < .05) for cells from this K/Q127, R/R131 individual than for Q/Q127, R/R131 donors. Platelet aggregation stimulated by an mIgG1 anti-CD9 antibody in this individual was significantly different (P < .05) from Q/Q127, H/R131 and Q/Q127, H/H131 donors and similar to Q/Q127, R/R131. Our data show that the K127/R131 receptors have a unique phenotype, binding both hIgG2 and mIgG1. Further functionally significant mutations in human Fc gamma receptors and possible novel mechanisms for inherited differences in disease susceptibility should be sought with unbiased screening methods.     

Hepatic failure and liver cell damage in acute Wilson''s disease involve CD95 (APO-1/Fas) mediated apoptosis

We gave auditory examples of two semantic categories through headphones to 100 surgical patients anaesthetized with propofol and enflurane. This presentation was made during certain stages of the procedure, potentially associated with arousal, and during steady-state anaesthesia. Postoperative review using category generation tests showed successful priming in a pre-induction group but no evidence of implicit memory in the anaesthetized groups. These results suggest that timing an auditory input to coincide with surgical stimulation does not increase the probability of retrieval of information by this type of testing.     

Comparative effects of the dual metallopeptidase inhibitor, MDL 100,240 and of enalaprilat on regional and on cardiac haemodynamics in conscious, hypertensive, transgenic ((mRen-2)27) rats

1. Heterozygous, male, hypertensive, transgenic ((mRen-2)27) rats (350-450 g) were instrumented for the measurement of regional or cardiac haemodynamics (n = 16, in both groups). Animals were given continuous i.v. infusions of the angiotensin-converting enzyme inhibitor, enalaprilat, or the dual metallopeptidase inhibitor, MDL 100,240 (both at 3 mg kg-1, 3 mg kg-1 h-1; n = 8 for regional and cardiac haemodynamics), for 32 h. Twenty four hours after the onset of infusion of enalaprilat or MDL 100,240, the bradykinin (B2)-receptor antagonist, Hoe 140 (1 mg kg-1, i.v.), was given and measurements were continued for a further 8 h, to assess any possible involvement of bradykinin. 2. Over the first 8 h of infusion, both enalaprilat and MDL 100,240 had significant antihypertensive effects, accompanied by similar regional vasodilatations. However, the blood pressure lowering effect of MDL 100,240 (-54 +/- 9 mmHg) was greater than that of enalaprilat (-38 +/- 4 mmHg), because the former caused a significantly greater reduction in cardiac index. 3. Between 8-24 h after the onset of infusion, there was a reduction in the effect of enalaprilat on blood pressure, because cardiac index rose, with no further increase in total peripheral conductance. In contrast, the antihypertensive effect of MDL 100,240 persisted, in spite of a recovery in cardiac index, because there was further vasodilatation, particularly in the mesenteric and hindquarters vascular beds. 4. There were no apparent haemodynamic changes associated with the injection of Hoe 140, and over the following 8 h, the difference between the haemodynamic effects of enalaprilat and MDL 100,240 persisted; there was little evidence of suppression of the effects of either drug. 5. These results are more consistent with the antihypertensive effects of enalaprilat or MDL 100,240 in transgenic ((mRen-2)27) rats being due to suppression of angiotensin II production, than due to inhibition of bradykinin degradation. The additional effects of MDL 100,240 may be accounted for by inhibition of the degradation of natriuretic peptides reducing cardiac output, initially, and decreasing vascular tone, subsequently. Alternatively, the additional increase in vascular conductance following treatment with MDL 100,240 may represent an autoregulatory response to the reduced pressure.     

Cholinesterase inhibitors for Alzheimer's disease

New cholinesterase inhibitors capable of slowing the progression of Alzheimer's disease are being introduced at a rapid pace. In prescribing these drugs and setting realistic expectations for outcome, it is necessary to understand that they affect cholinergic activity in other tissues as well as the brain. They may be most effective when used in combination with other drugs.     

Cost-effectiveness of assertive community treatment teams

The long cane can be used as a mobility aid for visually handicapped people. According to a questionnaire completed by Japanese cane users, it seems they are not always satisfied with using long canes for a variety of reasons. In this study, hand-transmitted vibration from the long cane due to tapping the ground was measured because an exposure to repeated shock-type tapping vibration may affect the hand-arm system. A sighted female wearing a blindfold participated. The measurement was carried out in different conditions with three different ground materials both indoor and outdoors. The vibration at three axes of the cane grip and one axis at the wrist were measured. The pinch forces between an index finger and the grip were also measured using a strain gauge in order to observe how the vibration characteristics depend on the changing forces. Measurement, evaluation and assessment were based on the International Standard (ISO 5349). The estimated daily exposure time and the transmissibility were obtained in order to investigate the severity of the hand-transmitted vibration caused by the long cane. It was found that the characteristics of tapping vibration depend on different measurement conditions and the vibration might be associated with a health risk over a long life span.