Stem cell-derived interneuron transplants as a treatment for schizophrenia: preclinical validation in a rodent model.

An increasing literature suggests that schizophrenia is associated with a reduction in hippocampal interneuron function. Thus, we posit that stem cell-derived interneuron transplants may be an effective therapeutic strategy to reduce hippocampal hyperactivity and attenuate behavioral deficits in schizophrenia. Here we used a dual-reporter embryonic stem cell line to generate enriched populations of parvalbumin (PV)- or somatostatin (SST)-positive interneurons, which were transplanted into the ventral hippocampus of the methylazoxymethanol rodent model of schizophrenia. These interneuron transplants integrate within the existing circuitry, reduce hippocampal hyperactivity and normalize aberrant dopamine neuron activity. Further, interneuron transplants alleviate behaviors that model negative and cognitive symptoms, including deficits in social interaction and cognitive inflexibility. Interestingly, PV- and SST-enriched transplants produced differential effects on behavior, with PV-enriched populations effectively normalizing all the behaviors examined. These data suggest that the stem cell-derived interneuron transplants may represent a novel therapeutic strategy for schizophrenia.

Spontaneous thrombosis in mice carrying the factor V Leiden mutation.

A polymorphism in coagulation factor V, factor V Leiden (FVL), is the major known genetic risk factor for thrombosis in humans. Approximately 10% of mutation carriers experience clinically significant thrombosis in their lifetime. In a small subset of patients, thrombosis is associated with coinheritance of other prothrombotic gene mutations. However, the potential contribution of additional genetic risk factors in the majority of patients remains unknown. To gain insight into the molecular basis for the variable expressivity of FVL, mice were generated carrying the homologous mutation (R504Q [single-letter amino acid codes]) inserted into the endogenous murine Fv gene. Adult heterozygous (FvQ/+) and homozygous (FvQ/Q) mice are viable and fertile and exhibit normal survival. Compared with wild-type mice, adult FvQ/Q mice demonstrate a marked increase in spontaneous tissue fibrin deposition. No differences in fetal development or survival are observed among FvQ/Q, FvQ/+ or control littermates on the C57BL/6J genetic background. In contrast, on a mixed 129Sv-C57BL/6J genetic background, FvQ/Q mice develop disseminated intravascular thrombosis in the perinatal period, resulting in significant mortality shortly after birth. These results may explain the high degree of conservation of the R504/R506 activated protein C cleavage site within FV among mammalian species and suggest an important contribution of other genetic factors to the thrombosis associated with FVL in humans. (Blood. 2000;96:4222-4226)

Colors of Objects in the Field of the Double Quasi-Stellar Object 1146+111B,C.

Color images of faint objects were used to test two hypotheses for the quasi-stellar object (QSO) pair 1146+ 111B,C: gravitational lens or massive string. Blue, red, and near-infrared CCD (charge-coupled device) images of the field of this QSO pair were examined for gravitational lens multiple-image candidates for all four QSO's in the field (B, C, D, and E). No third image of 1146+111B,C was found, down to 4 magnitudes fainter than BC. This result implies a compact lens mass distribution, if B and C are images of the same QSO. C appears to be redder than B in the wavelength region from 700 to 1100 nanometers. This raises the question of whether B and C are images of the same QSO. Three blue stellar objects of unusual color were found at plausible locations for multiple images of the other two QSO's in the field. A very red object was found at a plausible lens position. Under the hypothesis that B and C are lensed images, these color data severely restrict the possible lens models and imaged QSO multiplicities. One possibility is a compact lens mass of 4 x 10(15) solar masses at a redshift of 0.8. Another is an S-shaped massive string. If the spectrum of any of the three anomalous blue objects were available, it would be possible to distinguish between these two models. However, it is difficult to fit the color and intensity data reported here to either simple string or black hole models. Overall, the simplest model consistent with all the data is the no-lens, no-string hypothesis: B and C probably are separate QSO's, but with some spectral similarities.

Fluorescent cytoplasm and Heinz bodies of hemoglobin Köln erythrocytes: evidence for intracellular heme catabolism.

Hb Köln, one of the common mutant hemoglobins responsible for unstable hemoglobin disease, was found to be degraded to a fluorescent yellow pigment (FYP) in circulating erythrocytes. FYP is responsible for a strong green fluorescence observed in the cytoplasm and is particularly abundant in the Heinz bodies of Köln RBC. Front face fluorometry and fluorescence microscopy showed that Heinz bodies emit 10% to 20% of the fluorescence of RBCs. Hb-free FYP was obtained by means of a cellulose column separation of the cytoplasm or from a precipitate formed during the incubation of Köln RBC cytoplasm at 50 degrees C. The absorption and emission spectra of FYP are consistent with those of dipyrroles.

Radiometer system to map the cosmic background radiation.

We have developed a 33-GHz airborne radiometer system to map large angular scale variations in the temperature of the 3 K cosmic background radiation. A ferrite circulator switches a room-temperature mixer between two antennas pointing 60 degrees apart in the sky. In 40 min of observing, the radiometer can measure the anisotropy of the microwave background with an accuracy of +/-1 mK rms, or about 1 part in 3000 of 3 K. The apparatus is flown in a U-2 jet to 20 km altitude where 33-GHz thermal microwave emission from the atmosphere is at a low level. A second radiometer, tuned to 54 GHz near oxygen emission lines, monitors spurious signals from residual atmospheric radiation. The antennas, which have an extremely low side-lobe response of less than -65 dB past 60 degrees , reject anisotropic radiation from the earth's surface. Periodic interchange of the antenna positions and reversal of the aircraft's flight direction cancel equipment-based imbalances. The system has been operated successfully in U-2 aircraft flown from NASA-Ames at Moffett Field, CA.