Decreased brain metabolism in neurologically intact healthy alcoholics.

OBJECTIVE: The extent to which cerebral dysfunction in alcoholics is related to the direct effects of alcohol in the brain rather than to indirect mechanisms and/or alcohol withdrawal remains unclear. The purpose of this study was to evaluate whether healthy alcoholics with no evidence of alcohol-associated complications showed changes in brain glucose metabolism. METHOD: Positron emission tomography and [18F]-fluorodeoxyglucose were used to measure regional brain metabolism. The study group consisted of 22 normal, healthy, right-handed volunteers and 22 neurologically intact, healthy, right-handed alcoholics tested 6 to 32 days after alcohol discontinuation. RESULTS: Alcoholics showed significantly lower whole brain metabolism than normal control subjects. Normalization of regional metabolic values to the whole brain metabolic rate revealed that the left parietal and right frontal cortices were the most affected regions. Although the whole brain metabolic rate was correlated with the amount of time since alcohol discontinuation, the "normalized" decreases in left parietal and right frontal glucose metabolism were not. CONCLUSIONS: These findings support the contribution of the direct effect of alcohol as well as alcohol withdrawal on the changes in regional brain metabolism seen in alcoholics. They also provide evidence of cerebral changes in neurologically intact healthy alcoholics.     

Donor eyes. A comparison of characteristics and outcomes for Eye Bank and local tissue

The Corneal Recipient Registry was begun in 1985 to collect information on all recipients of corneal grafts in the province of Ontario, Canada, and on the donors providing tissue. While most of the tissue is handled by the Eye Bank of Canada (Ontario Division), ophthalmologists in centers away from the Eye Bank often use local tissue when it is available. Comparison of the donor characteristics of local tissue with that obtained through the Eye Bank revealed that local donors were 9-10 years younger (p less than 0.01), their times to enucleation were an hour less (p less than 0.02), and they were much more likely to be the victims of trauma than the donors of Eye Bank eyes. Prognosis of the graft, assessed using life table methods, suggested that success of local eyes was 89% after 6 months, compared with 80% for Eye Bank eyes in the same period, but this was not a significant difference (p greater than 0.05). While the Eye Bank is a more common source of tissue, eyes obtained locally are more likely to represent the "ideal" tissue for many corneal surgeons.     

Propionyl coenzyme A carboxylase deficiency presenting as non-ketotic hyperglycinaemia.

A 4-month-old girl presented with myoclonic seizures and an electroencephalogram showing hypsarrhythmia. Hyperglycinuria and a cerebrospinal fluid to plasma glycine ratio of 0.2 suggested the diagnosis of non-ketotic hyperglycinaemia. Propionic acid and methyl citric acid were present in the urine, and propionyl coenzyme A carboxylase was deficient in leucocytes and fibroblasts. The ketotic and non-ketotic hyperglycinaemias cannot be differentiated by CSF: plasma glycine ratios.     

Postnatal development of the mouse dentate gyrus in organotypic cultures of the hippocampal formation

The hippocampal formation of newborn mice was explanted and maintained in Maximow culture assemblies for up to 35 days. At the time of explantation, only the suprapyramidal limb of the dentate gyrus was cytoarchitectonically distinct, and electron microscopy of newborn hippocampus revealed no definitive synapses. Histogenesis, as indicated by the development of the infrapyramidal limb of the dentate gyrus, and synaptogenesis, as indicated by the in vitro formation of mossy fiber synapses on the dendrites of hippocampal pyramidal neurons were studied by light and electron microscopy. At 12 days and thereafter in culture, mossy fiber terminals were found in synapsis with dendritic spines probably belonging to pyramidal cells of the hippocampal zone CA4. Near dentate granule cell somata a few axosomatic and many axospinous and axodendritic synapses were found. The data indicate that granule cells of the developing dentate gyrus are capable of differentiation in vitro into a structure essentially equivalent to that developed in vivo. The granule cells may become arranged into a recognizable granule cell layer, and develop dendritic processes which receive synapses virtually identical to those found in the intact organ. The differentiation of these features proceeds in the absence of the extrinsic afferents from the septum or from the contralateral hippocampal formation.     

Potentiation of lymph node antibody synthesis by normal thymus in vitro

Antibody formation during the secondary response in vitro was enhanced when normal thymus fragments from 1- to 2-week-old rabbits were coincubated with immune popliteal lymph node fragments. Although the addition of three thymus fragments to three lymph node isolates produced a significant increase in antibody synthesis, six or nine thymus fragments stimulated the response still further; normal spleen or normal lymph node did not stimulate. Radioactive amino acid incorporation into antibody confirmed that de novo antibody synthesis was potentiated by the thymus. In addition, increased synthesis of total globulins was quantitatively measured. The thymus seemed to enhance formation of only 7S immunoglobulin as determined by sucrose gradient centrifugation. It is not known whether thymus cells, humoral factors, or both participate in this response, or what intracellular metabolic events are being stimulated when the thymus is added to the cultures.     

CD5 (OKT1) augments CD3-mediated intracellular signaling events in human T lymphocytes

CD5 is expressed on thymocytes, all mature T cells, and a subset of mature B cells, and probably contributes to T-cell–B-cell adhesion. We assessed whether CD5-crosslinking by mAb augments T-cell stimulation. Plate-bound anti-CD5 or anti-CD3 mAb alone had no effect on any of the assessed activation parameters of resting T cells. However, concomitant signaling through both CD5 and CD3 by plate-bound antibodies resulted in marked increases in T-cell surface CD69 expression and T-cell metabolism, as assessed by the T cell's ability to reduce 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxylmethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium (MTS) to formazen. In addition, simultaneous cross-linking of CD5 and CD3 caused a significant (p < 0.001) increase in phosphatidylinositol hydrolysis in resting T cells compared to stimulation with anti-CD3 mAb alone or anti-CD3 mAb plus anti-CD5 isotype control antibody. These results indicate that CD5 augments signaling through CD3 and consequently functions as a costimulatory molecule for resting T cells.     

Susceptibility of mice to rotavirus infection: effects of age and administration of corticosteroids.

We examined susceptibility to the murine rotavirus, epizootic diarrhea of infant mice virus (EDIM), in normal suckling and weaned mice and in suckling mice treated with glucocorticoids. Normal mice 1 to 40 days old were inoculated by gastrin intubation with high doses of EDIM and subsequently evaluated for rotavirus infection by solid-phase radioimmunoassay, by electron microscopy of intestinal tissue sections or by both. Radioimmunoassay and electron microscopy showed a concordance of 89.5% in the detection of rotavirus infection. After a period of low susceptibility to EDIM infection during the first 3 days after birth (23%), susceptibility was high for the next 11 days (95%), but decreased abruptly as mice approached weaning (41% on days 15 through 17). Mice 34 days or older did not develop EDIM infection after inoculation, but rotavirus antigen was detected in 12% of uninoculated mothers nursing inoculated litters. Administration of cortisone acetate to 8-day-old mice induced partial intestinal maturation prematurely. At 3 to 6 days after cortisone acetate treatment, susceptibility to EDIM infection decreased to 60% compared with 94% in age-matched controls. Our data suggest (i) that susceptibility of mice to EDIM infection is age dependent, decreasing in concert with intestinal maturation, and (ii) that glucocorticoids, which induce premature partial intestinal maturation, modulate susceptibility of mice to EDIM.     

A mixture of ammonium perchlorate and sodium chlorate enhances alterations of the pituitary-thyroid axis caused by the individual chemicals in adult male F344 rats

Ammonium perchlorate (AP) and sodium chlorate (SC) have been detected in public drinking water supplies in many parts of the United States. These chemicals cause perturbations in pituitary-thyroid homeostasis in animals by competitively inhibiting iodide uptake, thus hindering the synthesis of thyroglobulin and reducing circulating T(4) (thyroxine). Little is known about the short-term exposure effects of mixtures of perchlorate and chlorate. The present study investigated the potential for the response to a mixture of these chemicals on the pituitary-thyroid axis in rats to be greater than that induced by the individual chemicals. Adult male F-344 rats were exposed, via their drinking water, to the nominal concentrations of 0.1, 1.0, 10 mg/L AP or 10, 100, 1000 mg/L SC and their mixtures for 7 days. Serum T(4) levels were significantly (p < 0.05) reduced in rats following exposure to the mixtures, but not after exposure to the individual chemicals. Serum T(3) (triiodothyronine) was not altered by treatment and TSH (thyroid stimulating hormone) was only increased after the high-dose chlorate treatment. Histological examination of the thyroid gland showed colloid depletion and hypertrophy of follicular epithelial cells in high-dose single chemical and all mixture-treated rats, while hyperplasia was observed only in some of the rats treated with mixtures (AP 10 + SC 100, AP 0.1 + SC 1000, and AP 10 + SC 1000 mg/L). These data suggest that short-term exposure to the mixture of AP and SC enhances the effect of either chemical alone on the pituitary-thyroid axis in rats.     

Gastrointestinal zygomycosis caused by Mucor indicus in a patient with acute traumatic brain injury.

We report a gastrointestinal infection caused by Mucor indicus in a patient with severe head injuries. Monotherapy with high-dose liposomal amphotericin B successfully eradicated the mucormycosis. Nevertheless, subsequently a hemicolectomy was necessary due to recurrent bleeding from a deep ulcer. Mucor indicus is an uncommon fungal pathogen, typically found in starters used for food fermentation. Reviewing other reports on Mucor indicus infections, primary gastrointestinal manifestations seem to be typical and indicate an oral route of infection.