Absence of chromosome heterogeneity between classical Fanconi's anemia and the Estren-Dameshek type

Chromosome investigations were carried out in 7 patients with Fanconi's anemia, type Estren-Dameshek. The frequency and types of chromosome instability found in cultured lymphocytes were in accord with those detected in individuals with classical Fanconi's anemia. The break-point distribution indicates a significant excess of breaks in chromosomes No. 1, 2, and 7 and a deficit in No. 18 and X and Y chromosomes. There was a clear clustering of breaks at certain locations in chromosomes No. 1, 2, 3, 7, 9, and 14. The location of the breaks with respect to the bands demonstrated an almost exclusive involvement of the lighter bands, regardless of the banding method used. These results suggest that most breaks take place in the interbands between the G and R bands. In all patients, chromosome instability was less frequent in direct bone marrow preparations than in lymphocyte cultures. However, cultured bone marrow cells showed a significant increase of chromosome aberrations. On the whole, the chromosome data derived from this series of patients are in agreement with those obtained in individuals with classical Fanconi's anemia and give no support to the idea of cytogenetic heterogeneity between subjects affected by these two forms of childhood aplastic anemia.     

Partial protective effect of CCR5-Delta 32 heterozygosity in a cohort of heterosexual Italian HIV-1 exposed uninfected individuals

Despite multiple sexual exposure to HIV-1 virus, some individuals remain HIV-1 seronegative (exposed seronegative, ESN). The mechanisms underlying this resistance remain still unclear, although a multifactorial pathogenesis can be hypothesised. Although several genetic factors have been related to HIV-1 resistance, the homozigosity for a mutation in CCR5 gene (the 32 bp deletion, i.e. CCR5-Delta32 allele) is presently considered the most relevant one. In the present study we analysed the genotype at CCR5 locus of 30 Italian ESN individuals (case group) who referred multiple unprotected heterosexual intercourse with HIV-1 seropositive partner(s), for at least two years. One hundred and twenty HIV-1 infected patients and 120 individuals representative of the general population were included as control groups. Twenty percent of ESN individuals had heterozygous CCR5-Delta 32 genotype, compared to 7.5% of HIV-1 seropositive and 10% of individuals from the general population, respectively. None of the analysed individuals had CCR5-Delta 32 homozygous genotype. Sequence analysis of the entire open reading frame of CCR5 was performed in all ESN subjects and no polymorphisms or mutations were identified. Moreover, we determined the distribution of C77G variant in CD45 gene, which has been previously related to HIV-1 infection susceptibility. The frequency of the C77G variant showed no significant difference between ESN subjects and the two control groups.     

Interaction design theory

OBJECTIVE: This paper presents a framework for the design of interactions between human and computational agents working in organisations, mediation by technological systems. DESIGN: The design of interactions within an organisation is viewed from the point of view, not of the technology mediating the new interaction, but of the human and computational agents who interact with each other. RESULTS: Understanding the limits to individual agent resources permits an analysis of the impact that a new interaction will have in a given setting. When we look beyond simple interaction settings, we can use the notion of interaction equilibria to predict the impact of new information and communication technologies within an organisation. Economic supply and demand curves, for example, may allow us to make both qualitative and quantitative predictions about technological adoption of communication systems. CONCLUSION: Rather than focusing solely on characteristics of individual technologies, or psychological and social issues, these can be combined to explain the overall decisions that individuals make when using technologies. Without necessarily understanding all the local decision criteria used by any individual, we can make robust predictions about how a group as a whole will interact.     

Chromaffin granules in the rat adrenal medulla release their secretory content in a particulate fashion

Exocytosis is considered the main route of granule discharge in chromaffin cells. We recently provided ultrastructural evidence suggesting that piecemeal degranulation (PMD) occurs in mouse adrenal chromaffin cells. In the present study, we processed rat adrenal glands for transmission electron microscopy (TEM), and examined chromaffin cells for changes characteristic of PMD. Both adrenaline (A)- and noradrenaline (NA)-storing cells express ultrastructural features suggestive of a slow and particulate mode of granule discharge. In adrenaline-containing cells, some granules present enlarged dimensions accompanied by eroded or dissolved matrices. Likewise, a number of granules in NA-releasing cells show content reduction with variably expanded granule chambers. Dilated, empty granule containers are recognizable in the cytoplasm of both cell types. Characteristically, altered granules and empty containers are seen intermingled with normal, resting granules. In addition, chromaffin granules often show irregular profiles, with budding or tail-like projections of their limiting membranes. Thirty 150-nm-diameter membrane-bound vesicles with a moderately electron-dense or -lucent internal structure are observable in the cytoplasm of both cell types. These vesicles are seen among the granules and some of them are fused with the perigranule membranes in the process of attachment to or budding from the granules. These data add further support to the concept that PMD may be an alternative secretory pathway in adrenal chromaffin cells.     

Metabotropic glutamate receptors are associated with non-synaptic appendages of unipolar brush cells in rat cerebellar cortex and cochlear nuclear complex

Unipolar brush cells (UBCs) are a class of small neurons that are densely concentrated in the granular layers of the vestibulocerebellar cortex and dorsal cochlear nucleus. The UBCs form giant synapses with individual mossy fibre rosettes on the dendrioles which make up their brush formations and are provided with numerous, unusual non-synaptic appendages. In accord with the glutamatergic nature of mossy fibres, our previous post-embedding immunocytochemical studies indicated that various ionotropic glutamate receptor subunits are localized at the post-synaptic densities of the giant synapses, whereas the non-synaptic appendages are immunonegative. On the contrary, the metabotropic glutamate receptors mGluR1 and mGluR2/3 are situated at the non-synaptic appendages and are lacking at the post-synaptic densities. Other authors, however, have shown that antibodies to these metabotropic receptors stain both appendages and post-synaptic densities. In the present study, we have re-evaluated the distribution of metabotropic glutamate receptors in the UBCs of the cerebellum and the cochlear nuclear complex by light and electron microscopic pre-embedding immunocytochemistry with subtype-specific antibodies. We confirm that UBCs dendritic brushes are densely immunostained by antibody to mGluR1 particularly in the cerebellum and that antibody to mGluR2/3 labels at least a percentage of the UBC brushes in both the cerebellum and cochlear nuclei. At the ultrastructural level, it appears that mGluR1 and mGluR2/3 immunoreactivities are not associated with the post-synaptic densities of the giant mossy fibre–UBC synapses, but instead are concentrated on the non-synaptic appendages of the cerebellar UBCs. The non-synaptic appendages, therefore, may be an important avenue for regulating the excitability of UBCs and mediating glutamate effects on their still unknown intracellular signal transduction cascades. We also show that the pre-synaptic densities of UBC dendrodendritic junctions are mGluR2/3 positive. As previously demonstrated, antibodies to mGluR1 and mGluR2/3 label subsets of Golgi cells. Antibody to mGluR5 does not stain UBCs in the cerebellum and cochlear nucleus and reveals the somatodendritic compartment of Golgi cells situated in the core of the cerebellar granular layer, whilst cochlear nucleus Golgi cells are mGluR5 negative.     

9q34 loss of heterozygosity in a tuberous sclerosis astrocytoma suggests a growth suppressor-like activity also for the TSC1 gene

Tuberous sclerosis is an autosomal dominant disease whose characteristicfeature is the development of multiple hamartomas in a varietyof organs and tissues. Two major loci have been identified sofar: TSC1 on chromosome 9q34 and TSC2 on chromosome 16p13.3.Loss of heterozygosity at 16p13.3-associated markers has beenrecently observed in hamartomatous lesions of some tuberoussclerosis patients. Here we report the first evidence of lossof heterozygosity at the TSC1 critical region in a giant cellastrocytoma of a familial tuberous sclerosis case. Segregationanalysis showed that the 9q34 haplotype lost carried the putativenormal TSC1 gene. These data support the hypothesis of botha germline and somatic loss-of-function mutation for the developmentof tuberous sclerosis hamartomas and suggest a tumor-suppressor-likeactivity also for the TSC1 gene product. Finally, the possiblesignificance of a second small region of loss of heterozygosityat 9p21, found in the same astrocytoma, is discussed.     

The detection of monocytes in human glomerulonephritis

Renal biopsy specimens from 343 patients with primary or secondary glomerulonephritis (GN) were examined for monocytes by the non-specific esterase reaction. Large numbers of monocytes per glomerulus (M/G) were found in essential cryoglobulinemia GN (29 pts, M/G 30.6 +/- 22.4), in acute post-infectious GN (27 pts, M/G 9.1 +/- 8.3), in rapidly progressive crescentic GN (20 pts, M/G 5.6 +/- 2.7), in systemic lupus GN (61 pts, M/G 5.0 +/- 5.6), and in IgA-GN associated with chronic liver disease (5 pts, M/G 6.4 +/- 5.9) or Sch?nlein-Henoch purpura (15 pts, M/G 3.3 +/- 6.4). Clinico-histological correlation showed that monocyte infiltration was correlated with the extent of proteinuria (all groups), with the presence of endoluminal "thrombi" (cryoglobulinemia GN), of polymorphonuclear leukocyte infiltration (post-infectious GN), of cellular crescents (crescentic GN), of "active" lesions (lupus GN), and with the extension of lesions to the peripheral capillary walls (IgA-associated GN). The M/G index was negligible in renal amyloidosis (21 pts), in idiopathic membranoproliferative GN (10 pts), in idiopathic IgA mesangial GN (63 pts), in membranous GN (40 pts), in focal glomerulosclerosis (29 pts), in minimal change nephropathy (18 pts), and in diabetic glomerulosclerosis (5 pts). The results confirm the participation of cells of the monocyte-macrophage series in the genesis of proliferative lesions, both intracapillary and extracapillary, in immune-mediated human GN and suggest their direct involvement in glomerular injury.     

Cellular uptake and metabolic reduction of pentavalent to trivalent arsenic as determinants of cytotoxicity and morphological transformation

Cytotoxicity, morphological neoplastic transformation, cellularuptake and metabolic reduction were determined in BALB/3T3 CIA31-1-1 cells for trivalent arsenic (sodium arsenite, As³⁺)and for pentavalent arsenic (sodium arsenate, As⁵⁺). The levelsof cellular uptake of⁷³As-labelled sodium arsenite and arsenatewere dose-dependent and highest in the first hour. At equimolarconcentration (3 x 10^–6 M), cellular uptake was 4-foldhigher for As³⁺ than for As⁵⁺. Cytotoxicity was higher for As³⁺than for As⁵⁺, but when correlated to total As cell burden itshowed no significant difference for the two forms. Morphologicaltransformation focus assays showed transforming activity forboth As³⁺ and As⁵⁺, with relative transformation frequenciesalso of 4:1. Recovery from the cytosol after exposure for 1–24h was >90% for either form of absorbed As. Exposure to As³⁺yielded 100% as As³⁺ in cytosol, but exposure to As⁵⁺ yielded>70% as As³⁺, showing a high rate of intracellular metabolicreduction. No methylated metabolites were detected by ion-exchangechromatography. After 24-h incubation in cell-free medium, oxidationof As³⁺ to As⁵⁺ occurred up to 30% of the dose, but incubationin the presence of cells lowered the oxidation level to 4%.As⁵⁺ was recovered unchanged from cell-free medium (24-h incubation),but in the presence of the cells it yielded up to 5% as As³⁺within 24 h and the cumulative release of As³⁺ by cells exposedto As⁵⁺ was dose-dependent. Glutathione depletion by diethylmaleateinhibited reduction of As⁵⁺ to As³⁺ by these cells up to 25%of controls, showing that As⁵⁺ reduction is partly dependenton glutathione. These results suggest that As³⁺ is the formresponsible for the cytotoxic and transforming effects, independentlyof the valence state of the inorganic arsenic in the culturemedium.     

Cesarean Delivery and Risk of Excess Weight Among Brazilian Preschool Children

Maternal and Child Health Journal - To study the relationship between cesarean Delivery (CD) and overweight in preschool children, considering the presence of birth aspects and demographic...