Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons

Neural stem cells are present both in the developing nervous system and in the adult nervous system of all mammals, including humans. Little is known, however, about the extent to which stem cells in adults can give rise to new neurons. We used immunocytochemistry, electron microscopy, fluorescence microscopy (FM imaging) and electrophysiology to demonstrate that progeny of adult rat neural stem cells, when co-cultured with primary neurons and astrocytes from neonatal hippocampus, develop into electrically active neurons and integrate into neuronal networks with functional synaptic transmission. We also found that functional neurogenesis from adult stem cells is possible in co-culture with astrocytes from neonatal and adult hippocampus. These studies show that neural stem cells derived from adult tissues, like those derived from embryonic tissues, retain the potential to differentiate into functional neurons with essential properties of mature CNS neurons.     

Thyroid autoimmunity

Antigenic structure remains a major focus in thyroid immunology. The genes for three major thyroid antigens--thyroglobulin, thyroid peroxidase and the thyrotropin receptor--were sequenced in the late 1980's, and epitopes for antibody and T cells have been reported within the last year. In addition, new evidence for selective use of T-cell receptor V gene segments in human thyroid infiltrates may point the way to specific immunotherapy.     

Characterization of an inversion duplication of the short arm of chromosome 8 by fluorescent in situ hybridization

A de novo chromosome aberration in a woman with severe mental retardation and minor anomalies has been characterized cytogenetically. The patient's karyotype was described as 46, XX, inv dup (8)(p12 → p23.1). Previous Southern blot dosage studies with the marker locus D8S7 demonstrated that the patient was monosomic for this locus, suggesting that the rearrangement generated a duplication-deficiency chromosome. We have reinvestigated this patient using fluorescent in situ hybridization with chromosome 8 cosmids and an Alu-PCR product specific for 8p. These studies have confirmed directly that the duplicated chromosome also has undergone deletion. © 1992 Wiley-Liss, Inc.     

Identification of semen in 500 patients seen because of rape

Of 500 patients seen because of rape, semen was identified in vaginal secretions by the identification of spermatozoa in 61%, by an acid phosphatase value of 50 units or more in 40%, and by the identification of a foreign blood group substance or a high titer of own blood group substance in 16%. The addition of the determination of the acid phosphatase to the search for spermatozoa identified semen in only 1.4% more patients, or a total of 62.4%. Identification and titers of blood group substance were confirmatory only, but further characterized the source of the semen in 25% of those patients with spermatozoa. Spermatozoa were identified for as long as 48 hours, and elevated acid phosphatase was not found after 18 hours. Acid phosphatase was elevated in only 62% of patients with spermatozoa.     

Development of glomerular filtration rate and electrolyte and osmolal clearance in the late-embryonic and newly hatched chicken

Summary Techniques have been developed for collection of urine in embryonic and newly hatched chickens for the purpose of studying the development of renal function.The reliability of EDTA-⁵¹Cr as a substitute for inulin-¹⁴C in the determination of GFR was studied. Since inulin and EDTA-⁵¹Cr clearances in the hatched chicken averaged 1.61±0.23 (S.E.) ml/min per kg body weight and 1.58±0.27 ml/min per kg body weight, respectively, EDTA-⁵¹Cr clearance was considered a suitable measure of GFR.GFR increased significantly in the first few days after hatching. Filtration rate was 0.068±0.008 (S.E.) ml/min per g kidney weight in the embryo and increased to 0.148±0.008 ml/min per g shortly after hatching. By nine days after hatching GFR had risen to 0.290±0.015 ml/min per g, a value comparable to that reported for the adult.Clearances of sodium, potassium, chloride and total osmolyte also increased with age. When these clearances were corrected for changing glomerular filtration rates the embryonic chicks were found to excrete a greater percentage of the filtered load. These results show that adult levels of glomerulo-tubular balance are not attained until after hatching.A preliminary report of this work has already been published [3].     

Stress and dental caries in the rat

The stress of crowding and exposure to inescapable electric shock increased both the incidence and the severity of dental caries in rats housed in a conventional animal facility. Male Osborne-Mendel rats were inoculated intraorally with cariogenic bacteria, fed a high-sucrose diet, and housed in either a conventional or a sheltered facility. Rats in both housing conditions were subdivided into control and stress groups. At the end of the 56-day trial period, stressed rats from conventional housing had a significant increase in both incidence and severity of dental caries in comparison to their controls. In contrast, stressed rats from sheltered housing had a trend toward increased cariogenesis which reached significance in only one of five scores. These rats also failed to gain weight comparable to their controls, making it possible that stress-induced reduction in appetite partially offset stress-induced exacerbation in cariogenesis.This investigation was supported in part by the following Grants from the United States Public Health Service: CA 20093, HL 22727, and HL 07374.     

Force enhancement by PEG during ramp stretches of skeletal muscle

We have investigated the effects of a stronger actomyosin bond on force (Ps) during rapid stretch of active permeabilized rabbit psoas muscle fibers as a function of temperature from 5 to 30 degrees C. The strength of the actomyosin bond is enhanced by addition of polyethylene glycol (PEG), especially in pre-powerstroke states [Chinn et al. (2000) Biophys J 49: 437-451]. We have hypothesized that such states produce much of the force when activated muscles are stretched [Getz et al. (1998) Biophys J 75: 2971-2983]. Addition of PEG to activated fibers produced a small increase in isometric tension, Po (50-90 kN/m2), which was approximately independent of temperature. In contrast PEG produced a dramatic increase in Ps at low temperatures (200-300 kN/m2), but a modest increase at higher temperatures (70-90 kN/m2). We also measured Ps and Po in solutions containing the phosphate analog aluminum fluoride (AlF4) with and without PEG. In the absence of PEG, AlF4 reduced Po much more than Ps. Addition of PEG did not enhance Po, but enhanced Ps significantly. The contrasting effects of PEG on Ps and Po, and the effect of temperature can be explained by a model in which stretch force is produced by pre-powerstroke cross-bridges whose maximum distension is increased by PEG, and isometric force is produced by strongly bound cross-bridges whose bond strength is also enhanced by PEG, but to a lesser extent.     

A membrane cofactor protein transgenic mouse model for the study of discordant xenograft rejection

Background:  In recent years, interest has been revived in the possibility of transplanting organs into humans from a phylogenetically disparate species such as the pig (xenotransplantation). Such discordant xenografts, however, are subject to hyperacute rejection (HAR) and activation of host complement plays a major role in this rejection. This problem may be solved through the use of transgenic technology by providing the grafted tissue with molecules that down-regulate the action of host complement.
Results: Transgenesis with a yeast artificial chromosome (YAC) was used to produce transgenic mice with the complete genomic gene of the human complement regulator membrane cofactor protein (MCP). Transgenic mice were obtained that exhibit full regulation of MCP as normally observed in humans. Hearts from these mice were shown to be significantly protected from HAR caused by human serum in an in vivo experimental procedure.
Conclusions:  We conclude that MCP can protect discordant xenografts from HAR caused by human serum and that transgenic mice can be used effectively as in vivo models for the study of the role of human complement regulatory molecules in xenotransplantation.