Amniotic fluid acetylcholinesterase measurements: comparing immunochemical and polyacrylamide gel techniques

In the present study, a recently reported immunochemical technique for measuring acetylcholinesterase (AChE) in amniotic fluid utilizing the 4F19 antibody was compared with the widely utilized polyacrylamide gel technique to determine whether the immunochemical assay provided an advantage in separating unaffected pregnancies from those associated with open spina bifida (OSB) and open ventral wall defects (OVWD). The study included (1) 73 amniotic fluid samples from unaffected pregnancies [alpha-fetoprotein (AFP) less than 2 MoM] with no visible gel AChE band, (2) nine bloodstained samples from unaffected pregnancies (AFP 2.2-4.0 MoM) with visible gel AChE bands, (3) 18 samples associated with OSB (AFP 2.2-7.0 MoM) with visible gel AChE bands, and (4) 20 samples associated with OVWD (AFP 3.2-53.5 MoM) with visible gel AChE bands. The immunochemical assay produced ranges of measurements in the four respective categories as follows: (1) 2-60 arbitrary units (AU): (2) 14-69 AU, (3) 61-593 AU, and (4) 22-476 AU. Eight of the nine unaffected pregnancies with visible gel AChE bands had immunochemical measurements below the highest measurement for the samples with no visible AChE band (60 AU), as did five out of 20 OVWD pregnancies. Two of the OSB cases had values of 61 and 62 AU. These data indicate that the 4F19 specific monoclonal antibody to AChE is capable of distinguishing unaffected from affected pregnancies with reasonable reliability but that more work needs to be done to establish the extent of overlap between the unaffected and affected populations.     

Immunological memory induced by genetically transduced tumor cells

Background: Recent studies have demonstrated the usefulness of gene-modified tumor cells for immunotherapy. Using the tumorigenic murine fibrosarcoma, MCA 106, we investigated the effects of localized interferon-γ (IFNg) secretion on tumorigenicity and on long-term memory. Methods: The murine IFNg (MuIFNg) gene was introduced into tumor cells. High and low IFNg-secreting clones were isolated. C57BL/6 mice were injected subcutaneously (s.c.) with either parental (P), high or low IFNg-secreting (H- or L-IFNg) cells, and tumor growth was assessed weekly. Spleens were harvested on different days postinjection (p.i.) to assess in vitro cytolytic activity. In parallel, tissues from injection sites were stained with macrophage-, CD4-, and CD8-detecting antibodies. Mice were injected s.c. with H-IFNg MCA106 tumor. After 150 days the animals were rechallenged s.c. with MCA106P in one leg and with irrelevant syngeneic tumor in the other. Results: Both P- and L-IFNg cells had similar growth, whereas the H-IFNg cells never grew. Only splenocytes from the H-IFNg animals showed in vitro CTL activity persisting until day 30 p.i. Histological data revealed a macrophage and CD4⁺ infiltrate much earlier in the H-IFNg group compared with the P group. Only the irrelevant, syngeneic tumor grew in animals previously injected with H-IFNg cells, whereas both P and irrelevant syngeneic tumors grew in controls. Conclusions: Transduction of MCA106 cells with the MuIFNg gene diminished in vivo tumorigenicity in proportion to the amount of IFNg secreted. Immunization with H-IFNg cells elicited a host response characterized by macrophages and CD4⁺ cells. Long-term tumor-specific memory was seen after immunization with H-IFNg cells.     

Neuropsychological and linguistic follow-up studies of children with galactosaemia from an unscreened population

Many galactosaemics appear to have neuropsychological and/or linguistic problems in spite of dietary treatment. Because the neonatal screening program in Norway does not include galactosaemia, we have re-examined Norwegian galactosaemics. Of 16 known patients, 8 patients participated in the study. They had been diagnosed between 2 and 11 weeks of age, and were between 9 months and 19 years old at the time of this study. All had very low or 0 activity of galactose-1-phosphate uridyl transferase. As part of the study all were examined neurologically, and had an age-appropriate developmental/IQ test, an ABR and an EEG, and a comprehensive psycholinguistic evaluation. The three youngest patients had normal developmental/IQ tests, while the five older patients had IQ scores in or below low range of normal. The majority had delayed language development and three patients were classified as having verbal dyspraxia. ABR and EEG showed mild pathology in the oldest patient only. Galactosaemia appears to be associated with significant risks of developmental and language delays in this unscreened population.     

The effect of chloroquine on the binding, intracellular distribution, and action of insulin on isolated mouse pancreatic acini

The effects of chloroquine on the binding, intracellular distribution, and action of insulin were studied in isolated pancreatic acini prepared from diabetic mice. Chloroquine had three effects on these cells. First, chloroquine altered cellular morphology by inducing an increase in the number and size of autophagic vacuoles and vesicles in the Golgi-lysosomal region. Second, chloroquine, in a dose-dependent fashion, increased the amount of 125I-insulin associated with acini. A detectable effect of chloroquine was seen at 10 microM, and a maximal effect was seen at 30-100 microM where cell-associated insulin was more than doubled. Employing electron microscope autoradiographs, this accumulation of hormone was observed in the Golgi-lysosome area of the pancreatic acinar cell. Third, chloroquine had selective effects on the action of insulin. Preincubation with chloroquine had no effect on basal [3H]2-deoxy-D-glucose uptake, but in a dose-dependent fashion it decreased the stimulatory effect of insulin on this function; at 100 microM chloroquine, the effect of insulin was abolished. In contrast, chloroquine had negligible effects on the stimulation of 2-deoxy-D-glucose uptake into acini by cholecystokinin. Chloroquine in dose-dependent fashion partially inhibited basal [3H]leucine incorporation into acinar cell protein, but in contrast to its effects on 2-deoxy-D-glucose uptake, the drug had no effects on the stimulation of this function by insulin.+2     

Alternatives to psychiatric hospitalization for children

The impetus for the dramatic increase in the number of treatment alternatives for children has come from changes in the theoretical conceptualization of treatment, social and political pressures, and financial considerations. This article reviews the literature on alternatives to hospitalization, appraising the available data on the effectiveness of psychiatric hospitalization and its alternatives and considers future research needs and the development of services in this area.