Detection of blood Gb3 deposits as a new tool for diagnosis and therapy monitoring in patients with classic Fabry disease.

BACKGROUND: The X-linked Fabry disease (FD) is a multiorgan disorder due to alpha-galactosidase A (α-GAL) deficiency with consequent lysosomal accumulation of globotriaosylceramide (Gb3). We established the immunocytochemical detection of Gb3 in blood cells of FD patients as a new method for FD diagnostics, follow-up and treatment control. METHODS: We enrolled 67 FD patients (37 men, 30 women) and 52 healthy controls (26 men, 26 women). PBMC were isolated from whole venous blood and 3x105 cells were immunoreacted with antibodies against CD77 as a marker for Gb3. Using fluorescence microscopy, the mean percentage of Gb3 positive PBMC was determined by an investigator blinded to subject allocation. As a second method, we qualitatively assessed Gb3 positive cells in blood smears. RESULTS: Gb3 deposits were unequivocally visible in PBMC and in blood smears. Men (P < 0.001) and women (P < 0.01) with classical FD had more Gb3-positive PBMC than healthy controls, whose samples only occasionally showed positive cells. The number of Gb3 positive PBMC was negatively correlated with α-GAL activity and positively correlated with plasma lyso-Gb3 levels. Only the PBMC Gb3 load but not plasma lyso-Gb3 reflected short- and long-term effects of enzyme replacement therapy (P < 0.01). CONCLUSIONS: Gb3 can be visualized in PBMC and blood smears and can be used as a novel marker for diagnostics, follow-up and treatment control in FD.

Cross-modal source monitoring confusions between perceived and imagined events.

Two experiments tested the prediction based on the source monitoring framework that imagination is most likely to lead to false memories when related perceived events have occurred. Consistent with this, people were more likely to falsely remember seeing events when the events had been both imagined as seen and actually heard than when they were just heard, just visually imagined, or imagined both visually and auditorily. Furthermore, when people considered potential sources for memories or more carefully evaluated features of remembered events, source errors were reduced. On average, misattributed ("false") memories differed in phenomenal qualities from true memories. Taken together, these findings show that as different qualities of mental experience flexibly enter into source attributions, qualities derived from related perceptual events are particularly likely to lead to false claims that imagined events were seen, even when the event involves a primary modality (auditory) different from the target event (visual).

Monomolecular organization of the main tetraether lipid from Thermoplasma acidophilum at the water-air interface.

The monomolecular organization of the main tetraether phospholipid from the archaeon Thermoplasma acidophilum was studied by means of a Langmuir film balance integrated into a fluorescence microscope. After transfer to solid surfaces at different pressures the films were further investigated by ellipsometry, small angle X-ray scattering and atomic force microscopy. In order to complete former results about the main tetraether phospholipid of T. acidophilum [Strobl, C., Six, L., Heckmann, K., Henkel, B., Ring, K., 1985. Z. Naturforsch. 40c, 219-222], the thickness and the two-dimensional organization of the monomolecular films were investigated. Two mean heights values were determined, one of 1.5-1.8 nm and another one of 4-5 nm, indicative for two different molecular arrangements. The former one is interpreted as a 'horseshoe' organization with two polar endings in the aqueous subphase, whereas the latter appears to represent the upright population of molecules with one polar end in the subphase and the other one in the air. In freshly spread and compressed films small domains of the upright lipid population are initially observed, which enlarge with increasing pressure. These domains are no longer existent after 12 h of spreading without compression.

Aging and source monitoring: cognitive processes and neuropsychological correlates.

This study shows that relative to younger adults, older adults are more adversely influenced by similar items when judging a memory's source, and the phenomenal features of their correctly and incorrectly attributed memories have greater overlap. The authors argue in accordance with the source monitoring framework that this age-related impairment in source accuracy is related to processes involved in binding features into complex memories and those involved in accessing and evaluating contextual features of memories. These processes are linked to medial temporal and frontal brain regions, respectively, as evidenced by correlations in older adults between source accuracy and neuropsychological tests often used to assess medial temporal and frontal function. The results suggest that adequate feature binding is particularly important when items from different source share similar features and access-evaluation processes are particularly important after a delay.

Reality monitoring of physically similar and conceptually related objects.

Three studies showed that information used in determining a target memory's source may be derived not only from the target event itself, but also from other nontarget events or memories. Subjects were more likely to claim that an imagined object was perceived when it physically resembled or was conceptually related to another specific item that was actually perceived, relative to when there was no physical resemblance or semantic relation. Furthermore, error rates for imagined items increased with the number of perceived items that they resembled. However, subjects' orienting task at encoding (perceptually biased or perceptually plus conceptually biased) did not systematically affect error rates. The results indicate that reality monitoring decisions about a target object are influenced by similar physical and conceptual information that was derived from other objects.

Comments on "Measuring memory for source: Some theoretical assumptions and technical limitations".

Researchers must consider limitations and assumptions inherent in their measure of source monitoring when drawing conclusions, an important point raised by Murnane and Bayen (1998). However, the issues they raise do not invalidate the conclusions we draw from the findings reported in Henkel and Franklin (1998). Issues regarding conclusions about source monitoring performance, the relation between recognition and source accuracy, and the use of empirical and multinomial analyses are discussed.

Treatment of diabetic (neuropathic) foot ulcers with two-stage debridement and closure.

We reviewed 33 patients with 37 wounds treated between November of 1991 and December of 1995 in the Wound Care Center. A two-stage debridement and closure technique for neuropathic foot ulcers was performed. Patients selected included those with obvious osteomyelitis and those who had failed nonsurgical treatment. The approach included initial surgical excision of the ulcer with biopsy, bone resection with biopsy, and deep culture. The second-stage procedure 4 to 8 days later included debridement of the wound and delayed closure. Intravenous antibiotic treatment using a central line was given postoperatively in patients with documented osteomyelitis for at least 6 weeks and in patients with infected soft tissues only for about 4 weeks. All patients remained nonweightbearing for 4 weeks; this was felt necessary to prevent separation of the wound edges. Four wounds in four patients failed to heal, and two of these went on to amputation. Satisfactory healing occurred in 29 of 33 patients and in 33 of 37 wounds. The authors conclude that two-stage surgical debridement and closure is an acceptable treatment in selected nonhealing diabetic (neuropathic) foot ulcers.

Evaluating characteristics of false memories: remember/know judgments and memory characteristics questionnaire compared.

Subjects hearing a list of associates to a nonpresented lure word later often claim to have heard the lure (Deese, 1959; Roediger & McDermott, 1995). To examine the characteristics of such false memories, subjects completed a memory characteristics questionnaire (MCQ; Johnson, Foley, Suengas, & Raye, 1988) or made remember/know (RK; Gardiner & Java, 1993) judgments for previously heard theme associates and nonpresented lures. MCQ ratings indicated that false memories for lures had less auditory detail and less remembered feelings and reactions than memories for presented words. In addition, rates of false recognition for lures were significantly lower than rates of correct recognition when items from various themes were intermixed instead of blocked at acquisition and subjects made MCQ ratings instead of RK judgments. This demonstrates that false memories can be affected both by how they are acquired and by how extensively they are examined at retrieval.

Parsing surrounding space into regions.

Surrounding space is not inherently organized, but we tend to treat it as though it consisted of regions (e.g., front, back, right, and left). The current studies show that these conceptual regions have characteristics that reflect our typical interactions with space. Three experiments examined the relative sizes and resolutions of front, back, left, and right around oneself. Front, argued to be the most important horizontal region, was found to be (a) largest, (b) recalled with the greatest precision, and (c) described with the greatest degree pf detao. Our findings suggest that some of the characteristics of the category model proposed by Huttenlocher, Hedges, and Duncan (1991) regarding memory for pictured circular displays may be generalized to space around oneself. More broadly, our results support and extend the spatial framework analysis of representation of surrounding space (Franklin & Tversky, 1990).