Characterization of estrogen receptor from human liver

Characterization of the estrogen receptor in cytosol from human male liver was undertaken to further understanding of the molecular basis of estrogen action in this tissue. By analysis of estrogen binding data of crude cytosol, saturable estrogen binding showed a Kd = 4.7 X 10(-10) M. High levels of nonsaturable binding were also detected. The estrogen-binding activities detected could be distinguished by their steroid specificity, hydrodynamic parameters, ionic properties, and sensitivity to proteolytic attack. Our findings also confirmed that the moderate-affinity estrogen binders found in rodent liver cannot be detected in human tissue. We concluded that the properties of estrogen receptor of human liver cytosol allow its separation from nonsaturable estrogen-binding components.     

Modulation of in vitro natural cell-mediated activity against enteropathogenic bacteria by simple sugars.

Lymphoid cells from mouse Peyer's patches and spleens were tested in a 2-h in vitro assay for their natural activity against the enteropathogenic bacteria Salmonella typhimurium, Salmonella enteritidis, Salmonella tel aviv, and Shigella sp. X16. The antibacterial activity expressed by normal cells was detected against all the bacterial strains tested with the exception of Peyer's patch lymphocytes against S. tel aviv and splenocytes against Shigella sp. X16. To determine whether the different expression of natural antibacterial activity might be due to lectin-like proteins interacting with the saccharidic moieties of the bacterial wall, 11 simple sugars were preincubated with the effector cells before the in vitro assays. We found that some of them could block the natural antibacterial activity as well as induce antibacterial activity when this was not spontaneously expressed. Interestingly, a different panel of sugars among those employed was observed to affect the antibacterial activities for each of the above-mentioned bacterial targets and each effector cell. However, the same panel of sugars was able to block or stimulate the lymphocyte activity when bacteria with the same somatic antigens as two substrains of S. typhimurium and one strain of Salmonella schottmuelleri were employed. To further investigate the interaction between effector cells and bacteria, effector cells or Shigella sp. X16 targets were treated with proteolytic, glycolytic, and lipolytic enzymes before the in vitro assays. Furthermore, EDTA was used to analyze the role of divalent cations in this experimental system. The results obtained suggest that lectin-like proteins playing a role in this interaction are present not only on lymphocytes but also on bacteria and that divalent cations are essential for the expression of in vitro antibacterial activity.     

Production of type-1 and type-2 cytokines by peripheral blood mononuclear cells of psoriatic patients.

We investigated the function of peripheral blood mononuclear cells (PBMC) in 16 patients with active psoriasis, in 15 patients with static psoriasis and in 27 healthy volunteers, by examining in vitro proliferation and antigen- and mitogen-stimulated production of interleukin-2 (IL-2) and IL-4. Plasma levels of the neuropeptide substance P were also determined. Defective alloantigen (ALLO)- and phytohaemagglutinin (PHA)-stimulated IL-2 production was detected in 42% and in 45% of psoriatic patients, respectively. The number of defective IL-2 responders was higher in static (60%) than in active (25%) psoriasis. The reduction of IL-2 responses in the former group was associated with an increase of IL-4 production. Thus PBMC of 66% of patients with static psoriasis but none of the patients with active psoriasis produced elevated amounts of PHA-stimulated IL-4. Variations of plasma substance P levels followed the same pattern of IL-4, being higher in static than in active psoriasis. These observations suggest a co-ordinated action of IL-4 and substance P as modulators of the clinical course of psoriasis. Our data show a possible correlation between the clinical evolution of psoriasis and the production of type-1 and type-2 cytokines, suggesting that the former may have a prominent role in the activation of psoriasis, while the latter may play a protective role.     

Cell surface CD28 levels define four CD4+ T cell subsets: abnormal expression in rheumatoid arthritis

CD28 is a costimulatory receptor expressed in most CD4(+) T cells. Despite the long-standing evidence for up- and downregulation of surface CD28 expression in vitro, and the key regulatory role assigned to the upregulation of CD28 counterreceptor [the CD152 (CTLA-4) molecule], in vivo CD28 induction has attracted little attention. We studied CD28 and CD152 expression and function in 33 rheumatoid arthritis (RA) patients, 20 clinically active and 13 inactive, and in 24 healthy donors. Four subsets of CD28(-), CD28(low), CD28(int), and CD28(high) peripheral blood human CD4(+) T cells were defined using three-color flow cytometry. The three CD28(+) subsets displayed a one-, two-, or threefold quantitative difference in their relative number of CD28 antibody binding sites, respectively (P < 0.01). RA patients, whether active or inactive, showed a distinct phenotype when compared to healthy donors: (i) the percentage of CD4(+)CD28(high) cells was increased twofold and the CD4(+)CD28(low) subset was reduced twofold (P < 0.01) and (ii) the CD4(+)CD28(high) cells from RA patients showed an in vivo activated phenotype, CD45RO(+)CD5(high)IL-2Ralpha(+) (P < 0.01). Active RA patients were different from inactive patients. They showed a twofold increase in mean CD28 expression (P < 0.05), whereas each of the CD28(+) subsets in the inactive RA patients showed reduced expression when compared to healthy donors. Notably, both active and inactive RA patients showed abnormal CD28 upregulation when T cells were activated in vitro with CD3 antibodies, but only inactive RA patients showed a hypoproliferative response to TCR/CD3 triggering when compared to healthy donors (P < 0.01). This defective proliferation was normalized by concurrent crosslinking with CD28 antibody. No differences were noted in the expression of CD152 or CD80, a CD28 and CD152 shared ligand. The disregulated in vivo expression of CD28 was related to the RA patients' disease activity and suggests that modulation of CD28 surface levels may be an additional mechanism to finely tune the delicate responsiveness/tolerance balance.     

Pericentric inversions of chromosome 4: report of a new family and review of the literature

A family was cytogenetically studied because of the birth of a male child with a multiple congenital anomaly pattern, in whom a dup (4q) recombinant was found. His phenotypically normal mother's karyotype showed an apparently balanced pericentric inversion in a chromosome 4. So as to analyze the occurrence of recombinants, the cytogenetic data from this family are compared with those of the 18 previously reported familial cases of pericentric inversions (PIs) of chromosome 4. The congenital anomalies observed in the child strongly suggest Wolf-Hirschhorn syndrome but some of his clinical features seem to be pathogenetically related to the presence of lymphedema during the intrauterine period. In the multiple congenital anomaly pattern observed in this patient, the lymphedema could be the consequence of the large 4q duplication. The review of chromosome 4 PIs with 4q duplication suggests that the q3 region should be examined when edema is detected prenatally.     

Speech suppression without aphasia after bilateral perisylvian softenings (bilateral rolandic operculum damage)

The authors describe a patient who suffered two successive, right and left, strokes that caused bilateral rolandic operculum damage. The clinical picture was characterized by selective impairment of volitional facio-pharyngo-glosso-masticatory movements with sparing of automatic and reflex motor activity (Foix-Chavany-Marie syndrome). Though completely speechless, the patient was not aphasic. This dissociation is discussed in the light of the peculiar localization of lesions evidenced by CT-scan.

---

Sommario Viene descritta una paziente portatrice di due lesioni ischemiche coinvolgenti l'opercolo rolandico in entrambi gli emisferi. Il quadro clinico era caratterizzato da una compromissione selettiva dei movimenti volontari (con integrità di quelli automatici e riflessi) bilateralmente a livello facio-faringo-glosso-masticatorio (sindrome di Foix-Chavany-Marie). La paziente, del tutto incapace di articolazione e fonazione, non risultava afasica ad una valutazione neuropsicologica. Questa dissociazione viene discussa in riferimento alla particolare localizzazione delle lesioni alla T.A.C. cerebrale.