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.     

Double mutation (A171T and D444H) is a common cause of profound biotinidase deficiency in children ascertained by newborn screening the the United States. Mutations in brief no. 128. Online

Biotinidase deficiency is inherited as an antosomal recessive trait that, unless treated with pharmacologic doses of biotin, can result in neurologic and cutaneous symptoms. We have identified two new mutations in exon D of the biotinidase gene of children with profound biotinidase deficiency ascertained by newborn screening. Transition 511G->A near the 5' end of exon D results in a substitution of threonine for alanine 171 (A171T) and transversion 1330G->C occurs close to the 3' end of exon D causing a substitution of histidine for aspartic acid 444 (D444H). The D444H mutation was detected in four individuals from our normal population whose mean serum biotinidase activity is 5.25 nmol/min/ml, which is significantly lower than the mean normal activity (7.1 nmol/min/ml). We calculated that this mutation causes a 52% loss of activity in the aberrant enzyme. Twenty-three individuals with the D444H mutation were found by allele specific oligonucleotide analysis of DNA from 296 randomly-selected, anonymous dried-blood spots. We estimate the frequency of this allele in the general population to be 0.039. In contrast, no individuals in 376 have the A171T mutation. Fourteen children (eleven probands and three siblings) out of the 31 enzyme-deficient children have both the A171T and D444H mutations. Both mutations are inherited from a single parent as a double mutation allele. The nine families in which this allele was identified are of mostly European ancestry, although the mutation cannot be attributed to a specific nationality or ethnic group. The serum of a child who is homozygous for the double mutation allele has very little CRM and the aberrant enzyme has very low biotinylhydrolase activity and no botinyl-transferase activity. This double mutation allele (A171T and D444H) is a common cause of profound biotinidase deficience in children ascertained by newborn screening in the United States.     

Severe early malnutrition and DRL performance in the rat

Rats with a history of severe early malnutrition (6% casein) were compared to well-fed control animals on an ascending series of DRL values ranging from 5 to 60 seconds. The 6% rats who were dietarily-rehabilitated at weaning did not differ from control animals in efficiency, responses per reinforcement or response rate. In contrast, rats chronically exposed to 6% diets performed so poorly during training with continuous reinforcement that they did not advance to even the first DRL (5-sec) condition. These findings show that severely-undernourished rats can perform within normal limits on even high DRL values, provided they are well trained and that they have adequate nutritional rehabilitation.     

The role of central parts of the brain in the control of sound production during courtship in Drosophila melanogaster

The question of the roles of the two main parts of the insect brain, the mushroom bodies and the central complex, in controlling motor coordination and triggering a variety of behavioral programs, including sound production, remains controversial. With the aim of improving our understanding of this question, we studied the parameters of songs used by five-day-old males during courtship for fertilized wild-type females (Canton-S, C-S) over 5-min periods at 25°C; males were of two wild-type Drosophila Melanogaster lines (Berlin and C-S). Berlin males lacking mushroom bodies because of treatment with hydroxyurea during development (chemical removal of the mushroom bodies) were used, along with two mutants with defects in the mushroom bodies (mbm ¹ and mud ¹), two mutants with defects in the central complex (ccb ^KS127 and cex ^KS181), and mutant cxb ^N71 with defects in both the mushroom bodies and the central complex. The experiments reported here showed that courtship songs in males lacking mushroom bodies were virtually identical to those of wild-type males. The main parameters of pulsatile song in mutants mbm ¹ and mud ¹ (interpulse interval and train duration) were insignificantly different from those of the songs of wild-type flies, though the stability of the pulse oscillator was the same. Flies of these lines were no different from wild-type flies in terms of courtship success (percentage of copulating pairs in 10-min tests). Conversely, the songs of mutants with defects in the central complex differed from those of wild-type males. Firstly, there was degradation of the stability of the pulse oscillator and interpulse intervals were very variable. In addition, pulses were often significantly longer and appeared multicyclic, as in the well-known cacophony mutant, while the mean train duration was significantly shorter. Males of the line cex ^KS181 usually courted very intensely, though abnormal sounds were generally emitted. Mutants cex ^KS181 and ccb ^KS127 were significantly less successful in courtship than wild-type flies. These data show that the central complex appears to play a very important role in controlling song, while the mushroom bodies are not related to this function.