Reorganization of human cortical maps caused by inherited photoreceptor abnormalities

We describe a compelling demonstration of large-scale developmental reorganization in the human visual pathways. The developmental reorganization was observed in rod monochromats, a rare group of congenitally colorblind individuals who virtually lack cone photoreceptor function. Normal controls had a cortical region, spanning several square centimeters, that responded to signals initiated in the all-cone foveola but was inactive under rod viewing conditions; in rod monochromats this cortical region responded powerfully to rod-initiated signals. The measurements trace a causal pathway that begins with a genetic anomaly that directly influences sensory cells and ultimately results in a substantial central reorganization.     

Untersuchungen zur Methodik der Aktivitätsbestimmung der Kreatinphosphokinase

Zusammenfassung Es wurden eingehende Untersuchungen über die Methodik der Aktivitätsbestimmung der Kreatin-Phosphokinase mit Hilfe von reiner Kreatinphosphokinase und kreatinphosphokinase-haltigem Serum durchgeführt. Neben der Aktivitätsbestimmung über das in einer bestimmten Zeit aus Kreatinphosphat gebildete Kreatin wird vor allem die Bestimmung mit Hilfe des erstmals vonTanzer u.Gilvarg angegebenen DPNH-verbrauchenden optischen Testes empfohlen. Die Abhängigkeit der Reaktionsgeschwindigkeit im optischen Test von verschiedenen Faktoren wie Temperatur, ATP-, Magnesium-und Kreatinkonzentration und Anwesenheit von reduziertem Glutathion wurde geprüft und ein zur Bestimmung der Kreatin-Phosphokinase-Aktivität im Serum geeigneter Testansatz angegeben.Abkürzungen KPK Kreatinphosphokinase - HK Hexokinase - G-6-PDH Glucose-6-Phosphat-Dehydrogenase - PK Pyruvatkinase - LDH Lactatdehydrogenase - ATP Adenosintriphosphat - ADP Adenosindiphosphat - AMP Adenosinmonophosphat - PEP Phosphoenolpyruvat - GSH reduziertes Glutathion - DPN oxydiertes Diphosphopyridinnucleotid - DPNH reduziertes Diphosphopyridinnucleotid - TPN oxydiertes Triphosphopyridinnucleotid - TPNH reduziertes Triphosphopyridinnucleotid - TRAP Triäthanolamin-Hydrochlorid-NaOH-Puffer - TRIS Tris(hydroxymethyl)-amino-methan-HCl Puffer - EDTA Äthylendiaminotetraessigsäure, di-Na-Salz     

Cutaneous lymphocyte antigen expression on human effector B cells depends on the site and on the nature of antigen encounter

In contrast to T cells, information on skin-homing B cells expressing the cutaneous lymphocyte antigen (CLA) is sparse. CLA expression on human B cells was investigated among circulating immunoglobulin-secreting cells (ISC) and among antigen-specific antibody-secreting cells (ASC) elicited by parenteral, oral or rectal primary immunization, or by parenteral or oral secondary immunization with Salmonella typhi Ty21a. CLA expression was examined by combining cell sorting with an enzyme-linked immunospot assay. Among all ISC, the proportion of CLA(+) cells was 13-21%. Parenteral immunization induced antigen-specific ASC of which 13% were CLA(+), while oral and rectal immunizations were followed by only 1% of CLA(+) ASC (p<0.001). Oral re-immunization was followed by an up-regulation of CLA (34-48%) regardless of the route of priming. Parenteral re-immunization elicited ASC of which 9-14% were CLA(+). In conclusion, the expression of CLA on human effector B cells depends on the site of antigen encounter: intestinal stimulation elicits cells with no CLA, while parenteral encounter elicits significant numbers of CLA(+) cells. Even though primary antigen encounter in the intestine failed to stimulate CLA expression, up-regulation of CLA was found upon intestinal antigen re-encounter. These findings may be of relevance in the pathogenesis of some cutaneous disorders.     

Immunity and depression: Insomnia,Retardation, and reduction of natural killer cell activity

Depressed patients show a reduction of natural killer (NK) cell activity which may be associated with specific depressive symptoms. The present study demonstrated that sleep disturbance and retardation, but not other depressive symptoms, were negatively correlated with NK activity in 38 depressed patients. Specific behavioral changes in depression such as sleep disturbance and retardation were found to predict 16% of the variance of cytotoxicity levels in depression.     

A histopathologic study of gastric and small intestinal graft-versus-host disease following allogeneic bone marrow transplantation

Twenty-two stomach and 14 small intestinal biopsy specimens from 24 allogeneic bone marrow transplant recipients were reviewed to evaluate the histopathologic changes of graft-versus-host disease (GVHD) in these organs. Associations between these results and clinical symptoms and other biopsy results were sought. In both organs, single epithelial cell necrosis was found to correlate with GVHD. Gastric GVHD was diagnosed in eight patients and small intestinal GVHD in four. Gastric GVHD was characterized by nausea, vomiting, and upper abdominal pain without diarrhea (the latter being present in only two patients), while all four of the patients with small intestinal GVHD had upper gastrointestinal symptoms and diarrhea. These symptoms correlated with concurrent rectal biopsy findings; pathologic alterations were seen in only one of six specimens from patients with gastric GVHD but in three of four with small intestinal GVHD. These findings suggest that stomach biopsy may be necessary to diagnose GVHD in patients with upper gastrointestinal symptoms but no diarrhea and normal rectal biopsy specimens. Diagnostic problems may arise in the early posttransplantation period, when the effects of cytoreductive therapy may simulate GVHD, and in patients with gastrointestinal cytomegalovirus infection, which may also produce changes identical to those of GVHD.     

Elevated amyloid beta protein (Abeta42) and late onset Alzheimer's disease are associated with single nucleotide polymorphisms in the urokinase-type plasminogen activator gene

Plasma amyloid beta protein (Abeta42) levels and late onset Alzheimer's disease (LOAD) have been linked to the same region on chromosome 10q. The PLAU gene within this region encodes urokinase-type plasminogen activator, which converts plasminogen to plasmin. Abeta aggregates induce PLAU expression thereby increasing plasmin, which degrades both aggregated and non-aggregated forms of Abeta. We evaluated single nucleotide polymorphisms (SNPs) in PLAU for association with Abeta42 and LOAD. PLAU SNP compound genotypes composed of haplotype pairs showed significant association with AD in three independent case-control series. PLAU SNP haplotypes associated significantly with plasma Abeta42 in 10 extended LOAD families. One of the SNPs analyzed was a missense C/T polymorphism in exon 6 of PLAU (PLAU_1=rs2227564), which causes a proline to leucine change (P141L). We analyzed PLAU_1 for association with AD in six case-control series and 24 extended LOAD families. The CT and TT PLAU_1 genotypes showed association (P=0.05) with an overall estimated odds ratio of 1.2 (1.0-1.5). The CT and TT genotypes of PLAU_1 were also associated with significant age-dependent elevation of plasma Abeta42 in 24 extended LOAD families (P=0.0006). In knockout mice lacking the PLAU gene, plasma--but not brain--Abeta42 as well as Abeta40 was significantly elevated, also in an age-dependent manner. The PLAU_1 associations were independent of the associations we found among plasma Abeta42, LOAD and variants in the IDE or VR22 region. These results provide strong evidence that PLAU or a nearby gene is involved in the development of LOAD. PLAU_1 is a plausible pathogenic mutation that could act by increasing Abeta42, but additional biological experiments are required to show this definitively.     

Use of 3D reconstruction to correct for patient motion in SPECT

Patient motion occurring during data acquisition in single photon emission computed tomography (SPET) can cause serious reconstruction artefacts. We have developed a new approach to correct for head motion in brain SPECT. Prior to motion, projections are assigned to conventional projections. When head motion occurs, it is measured by a motion monitoring system, and subsequent projection data are mapped to 'virtual' projections. The appropriate position of each virtual projection is determined by applying the converse of the patient's accumulated motion to the actual camera projection. Conventional and virtual projections, taken together, form a consistent set that can be reconstructed using a three-dimensional (3D) algorithm. The technique has been tested on a range of simulated rotational movements, both within and out of the transaxial plane. For all simulated movements, the motion corrected images exhibited better agreement with a motion free reconstruction than did the uncorrected images. This technique may help to overcome one of the major remaining limitations on image quality and quantitative accuracy in SPECT.