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Biomedical subjects

C Ferrari

Publications and source records attributed to C Ferrari.

At least 127 records · Page 7Linked to original sources

The preS1 antigen of hepatitis B virus is highly immunogenic at the T cell level in man.

14 hepatitis B vaccine recipients who showed high titers of anti-hepatitis B surface antibodies in serum after booster immunization with a polyvalent hepatitis B surface antigen vaccine that contained trace amounts of hepatitis B virus (HBV) preS1 and preS2 envelope antigens were studied for their in vitro T cell response to these antigens. All 14 subjects displayed a significant proliferative T cell response to the S/p25 envelope region encoded polypeptide; 8 also responded to preS1, while only 1 showed a significant level of T cell proliferation to preS2. Limiting dilution analysis demonstrated that the frequency of preS-specific T cells in two of these vaccine recipients was higher than that of S/p25-specific T cells. T cell cloning was then performed and a total of 29 HBV envelope antigen-reactive CD4+ cloned lines were generated from two preS-responsive vaccines. 21 of these lines were S/p25 specific, 7 preS1 specific, and 1 preS2 specific. Taken together, all these results suggest that the preS1 antigen may function as a strong T cell immunogen in man.

Chromobox Protein Homolog 5

Cabergoline: long-acting oral treatment of hyperprolactinemic disorders.

Cabergoline, a new orally active dopaminergic drug with an extremely long-lasting PRL-lowering effect, was given to 48 hyperprolactinemic women for 3-18 months (median, 8 months) at doses varying between 0.2-3 mg/week administered one to three times weekly. Serum PRL levels declined to normal in 41 women, 30 of whom received 0.2-1 mg cabergoline once weekly, 8 received 0.2-0.5 mg twice weekly, and 3 received 0.4-0.6 mg 3 times weekly. Five women had slightly supranormal serum PRL levels while receiving 0.3-0.6 mg once weekly, but the dose was not increased because the lower dose had produced the desired clinical benefit. Two women had 50% reductions in their serum PRL levels, but remained hyperprolactinemic while receiving 2-3 mg cabergoline weekly. Among 30 amenorrheic women, 28 had resumption of menses, the exceptions being 2 hypopituitary women, presumptive evidence of ovulation was available in 21. Marked tumor shrinkage occurred after 3-month treatment in 5 of the 6 women who had macroprolactinomas. Only 4 women had side-effects during the first weeks of treatment, and these vanished despite continued cabergoline administration at the same or reduced, but still effective, doses. In a short term, double blind study, cabergoline at 3 different schedules (0.4 mg twice weekly, 0.2 mg 4 times weekly, and 0.4 mg 3 times weekly for 3 weeks, followed by 0.4 mg twice weekly) or placebo was given to a total of 24 hyperprolactinemic women (6 in each subgroup) for 8 weeks, with weekly evaluation of serum PRL levels and side-effects. All 3 cabergoline schedules, but not placebo, induced significant reductions in serum PRL concentrations during the 8-week treatment period. Mild transient side-effects occurred in 7 drug-treated patients (nausea in 5; dizziness in 3). We conclude that cabergoline is effective treatment for hyperprolactinemia. Its efficacy, tolerability, and long duration of action may make it the drug of choice for patients with hyperprolactinemia.

Administration, Oral

Diabetes and illness image: an analysis of diabetic early-adolescents' self-perception through the Draw-a-person test.

To study the self-projective representations expressed by diabetic children, aged between 10 and 15 yr., and to compare these with representations of a control group the Draw-a-person test associated with those for subsequent Draw-a-sick-person were administered to 23 children regularly checked by an Antidiabetic Centre. The diabetic subjects drew an image of "sick person" having projective elements with a regressive value and denoting a refuge in the past, together with depressive signs of retiring into themselves and of less consideration of the self. Also, the diabetic children seemed to be less prone to the cultural stereotype which requires a smiling and happy image of "the healthy person." At the same time there was also a transparent symbolic defense which allowed the diabetics to adapt variously and to move from their anxious state toward psychological recovery.

Adolescent

[Clinical experience on the use of total parenteral nutrition in patients subjected to radical cystectomy intervention for infiltrating neoplasms of the bladder].

The Authors report their 7 year follow-up on the use of T.P.N. in 28 patients treated surgically for infiltrating cancer of the bladder. They consider the pathogenetic mechanisms that influence the organism's adaptation to surgical stress with particular reference to the multiple neuroendocrinal and biochemical interconnections. The procedures to define the nutritional/metabolic levels, of the patients undergoing operation are exposed. The T.P.N. is given according to the personal requirements of each patient and is a function of the "performance status", caloric need and to the presence of sepsis. Problems concerning the radical cistectomy such as: time of surgery, extention of exeresis, uroentheroanastomosis, metabolic variations, sepsis, etc., are evaluated. Considering the positive results obtained with this nutritional procedure, the Authors underline the importance of a systematic use of T.P.N. wich should be included, in their opinion, in a multidisciplinar treatment of advanced bladder neoplasms.

Female

Further characterization of the "incipient lesion of chronic stationary type psoriasis vulgaris in exacerbation". The CD4-positive lymphocytes are the prominent cell population infiltrating the dermis.

In previous studies, others and we have demonstrated by immunohistological methods in light microscopy that the prominent cell population infiltrating the psoriatic lesional dermis is represented by CD4-positive cells, thus suggesting an implication of T4 lymphocytes in the development of psoriatic lesion. However, recent findings have indicated that not only T4 lymphocytes, but also macrophage-like cells, are CD4-positive. In the present study, therefore, a highly specific and sensitive 'in situ' gold-immunoelectronmicroscopy procedure developed by us was performed to identify ultrastructurally with precision the nature of the CD4-positive cells infiltrating the dermis of the incipient psoriatic lesion. Although a consistent proportion (28%) of slightly CD4-positive macrophage-like cells was detected, the strongly CD4-positive lymphocytes were the prominent cell subset (51%). The important role presumably played by such CD4-positive lymphocytes in the pathogenesis of the psoriatic lesion is discussed. Our gold-immunoelectronmicroscopy technique improved the study of psoriatic cell subpopulations in situ, since (a) in comparison with immunocytochemistry in light microscopy, it allowed us not only to recognize the ultrastructure of the labelled cells, but also to detect even small amounts of antigen on the cell surface; and (b) in comparison with the commonly used peroxidase immunoelectronmicroscopy techniques, it allowed us to quantitatively assess the expression of antigens (e.g. CD4) on different cell subpopulations (e.g. the low CD4 expression by macrophage-like cells versus the high CD4 expression by T4 lymphocytes).

CD4 Antigens

Functional modulation of hepatitis B core antigen-specific T lymphocytes by an autoreactive T cell clone.

Hepatitis B core (HBc)Ag-specific T cells present in the peripheral blood of a patient with chronic active hepatitis B were expanded by co-cultivation for 7 days with rHBcAg. After cloning at 1 cell/well in the presence of PHA and IL-2, five HBcAg-specific CD4+ cloned lines were obtained. All five lines proliferated and produced IL-2, IFN-gamma, and TNF in a dose-dependent fashion in response to HBcAg, but not to HBV envelope Ag. The cloned lines and derivative clones were HLA class II (DR1) restricted. All T cell clones were able to induce anti-HBc production by autologous B cells in response to HBcAg (helper effect). The proliferative response and the helper effect of the HBcAg-specific T cell lines and clones were augmented by co-cultivation with an autologous, autoreactive (HLA-DQ1 specific) T cell clone, even in the absence of HBcAg, and the autoreactive T cells directly stimulated anti-HBc secretion by autologous B cells, presumably due to the release of Ag-nonspecific factors. These findings define a model immunoregulatory circuit the physiologic significance of which remains to be determined.

Adult

Hairy cell leukemia cells express CD1a antigen.

Five patients with hairy cell leukemia (HCL) were studied. Peripheral blood leukocytes, rosette-forming cells (T) and non-T-cells were stained in immunofluorescence by a panel of monoclonal antibodies to investigate the phenotype of HCL cells (HCLC). In all patients HCLC showed B-lymphocyte phenotype, although they were not stained by antibodies reactive for monocytes, natural killer cells, or T-cells. However, in all instances the large majority of HCLC were unexpectedly stained with an antibody (anti-CD1a) usually detectable only in early thymocytes and on Langerhans cells. This finding was further confirmed by immunoelectron microscopy. This type of ambiguity in the lineage of HCL could imply that HCLC might arise from cells differentiated towards the B-cell lineage, still sustaining an early antigen of a different (T) lineage. These results, moreover, extend the range of the known distribution of the CD1a antigen, which could be useful in diagnosing HCL.

Antibodies, Monoclonal

Clinical features of hepatitis delta virus infection in a northern Italian area.

Expression of hepatitis delta virus (HDV) markers was investigated in sera from 310 patients with acute hepatitis, 63 chronic hepatitis B surface antigen (HBsAg) carriers and 76 drug addicts positive for at least one serological hepatitis B virus (HBV) marker. Acute HDV infection occurred in 17.1% of the patients with acute hepatitis. Among 40 cases of coinfection, hepatitis was severe in ten and fulminant in three. Only two of the 13 superinfected patients showed a severe hepatitis, but a high percentage (78%) of them developed chronic hepatitis one year after HDV infection. Also in our area parenteral drug addiction represents the main factor of risk for HDV infection. The high prevalence of HDV infection in our area points to the necessity for serological screening for HDV markers in patients with acute and chronic hepatitis.

Acute Disease

The S-100 beta protein in normal human peripheral blood is uniquely present within a discrete suppressor-T-cell compartment.

The S-100-positive T lymphocytes, and, particularly, the S-100 beta subunit, are restricted, as demonstrated by quantitative subset analysis and double-labeling (gold-peroxidase) immunoelectron microscopy of T-cell subpopulations, to an unique T8-positive cell subset which interestingly was 9.3-negative and CD11b-positive. Since both the T8-positive, 9.3-negative and the T8-positive, CD11b-positive subpopulations have been demonstrated to show suppressive activities, the S-100-positive T cells seem to be closely restricted to a small T-suppressor-cell compartment. Although functional studies on viable isolated S-100 beta-positive cells are impossible to achieve, due to the lack of this protein on the cell membrane, its presence in a discrete T-suppressor compartment might suggest a possible role for the S-100 beta-positive T cells in the regulation of the immune system.

Antigens, Differentiation, T-Lymphocyte

Cellular immune response to hepatitis B virus antigens. An overview.

It has been suggested that the cellular immune response to HBV antigens is responsible for hepatocellular injury in acute and chronic hepatitis B. However, definitive immunological studies have so far been hampered by the lack of appropriate model systems to study HBV antigen-specific T cells. The availability of highly purified and recombinant HBV antigens and of experimental techniques to maintain in continuous growth antigen-specific T cells derived not only from the peripheral blood but also from the liver should allow a better understanding of the fine immunopathogenetical mechanisms involved in viral clearance and liver damage. Whether some important biological characteristics of HBV antigens described in the mouse system, such as the high immunogenicity of the pre-S antigens and the capacity of the nucleocapsid of HBV to be a T cell-dependent and -independent antigen, are relevant to the immunopathogenesis of liver damage during natural HBV infection in man remains to be evaluated.

Animals

Immunoelectronmicroscopic demonstration of S-100 protein in hairy cell leukemia cells.

Hairy cell leukemia (HCL) is generally considered a neoplastic proliferation of B-cell lineage. Among immunocompetent cells, however, S-100 protein is also demonstrated in "dendritic" cells (i.e., interdigitating reticulum cells, Langerhans cells, follicular dendritic cells) and in a small percentage of T8-cells. This study reports the surprising detection of S-100 protein in peripheral blood HCL cells of B-cell type, using immunofluorescence and immunoelectronmicroscopy. However, negative results for S-100 protein staining were obtained in paraffin splenic sections of HCL cases. This report stresses the need for caution in the interpretation of immunocytochemical methods and results, and emphasizes the diagnostic ambiguity of the S-100 protein.

Blood Cells

Simultaneous colloidal gold immunoelectronmicroscopy labeling of CD1a, HLA-DR, and CD4 surface antigens of human epidermal Langerhans cells.

The simultaneous demonstration of three surface antigens of Langerhans cells (LC) within LC-enriched fresh epidermal cell suspensions from normal human skin was achieved, by means of a triple immunogold (IG) staining, using commercially available monoclonal antibodies (moAb) and immunoreagents, in a simple pre-embedding immunoelectronmicroscopy (IEM) procedure. As a result, suspended LC were triple-stained as follows: gold particles of 40 nm revealed the CD1 a antigen; gold particles of 20 nm revealed the HLA-DR antigen; and gold particles of 5 nm revealed the CD4 antigen. All the observed epidermal Birbeck granule-bearing LC were triple IG stained, thus simultaneously expressing the three surface differentiation antigens, which are therefore different from but coexisting with each other. The present investigation assesses the constant simultaneous expression by Birbeck granules bearing LC of not only CD1a and HLA-DR antigens, but also CD4 antigen. The occurrence is therefore excluded of both CD1a-positive HLA-DR-negative LC subpopulation and CD4-negative LC subpopulation, presumably due to the different sensitivity of the various procedures performed. The hypothetical occurrence of CD4-positive, CD1a-, and/or HLA-DR-negative LC subpopulations is ruled out. This study reaffirms indeed the high specificity and sensitivity of the IG-IEM method for a precise detection of the cell surface antigens of LC, and states the suitability of the IG labeling even for accurate multiple IEM stainings of LC.

Adult

Long-lasting lowering of serum growth hormone and prolactin levels by single and repetitive cabergoline administration in dopamine-responsive acromegalic patients.

Cabergoline, the new long-acting dopaminergic ergoline derivative, was given orally in single doses of 0.3 and 0.6 mg to eight dopamine-responsive acromegalic patients. Serum GH and PRL levels were determined before treatment, 3, 4, and 6 h and 1, 3, 5, 7 and 14 days after treatment. A control test with a single oral dose of 2.5 mg of bromocriptine was also performed. Cabergoline induced a marked fall in serum PRL level, starting within 3 h and continuing for 7 days after administering 0.3 mg, and for 14 days after 0.6 mg. The mean maximal decrease was 49% after 0.3 mg and 63% after 0.6 mg and occurred after 24 h in both cases. The latter was of similar magnitude to that induced by bromocriptine (67% at 4 h). Serum GH levels did not change after 0.3 mg of cabergoline, but decreased significantly from 3 h to 3 days after 0.6 mg of the compound with a mean maximal decrease of 42% after 24 h, and from 3 to 6 h after giving bromocriptine (mean maximal decrease 63% at 4 h). Once a week repeated administration of 0.3-0.6 mg of cabergoline was carried out in six patients, five of whom had completed the acute study; a normalization of serum GH and insulin-like growth factor I (IGF-I) levels occurred in three patients, one of whom had very high pretreatment values. In three poorly or nonresponsive patients, a better response, as assessed by both GH and IGF-I levels, was induced by increasing the dose up to 0.6 mg twice or 0.4 mg three times a week; in one case this was associated with marked tumour shrinkage. Sustained normalization of PRL levels was achieved in all cases. These data indicate that a single dose of 0.6 mg of cabergoline inhibits GH as well as PRL secretion in dopamine-responsive acromegalic patients and suggests that doses of 0.3-0.6 mg once to three times a week may prove suitable for treatment of this condition.

Acromegaly

Prolactin-lowering effect of acute and once weekly repetitive oral administration of cabergoline at two dose levels in hyperprolactinemic patients.

To further evaluate the potency and time course of the PRL-lowering effect of single oral doses of cabergoline, two doses of the drug were given to 51 hyperprolactinemic patients who also received 2.5 mg bromocriptine according to a randomized cross-over design. One group (n = 26) received 0.3 mg, and the other (n = 25) received 0.6 mg. Both cabergoline doses induced a significant fall in serum PRL levels, which lasted, on the average, from 3 h to 5 days after 0.3 mg and from 3 h to 14 days after 0.6 mg; the mean maximum decrease after 0.3 mg was -65 +/-4% (+/- SEM), significantly (P less than 0.05) less than that after bromocriptine (group mean, -73 +/- 4%), and it was -76 +/- 3% after 0.6 mg, not significantly different from that induced by bromocriptine (group mean, -71 +/- 4%). The effect of 0.6 mg cabergoline was significantly greater than that of 0.3 mg (P less than 0.01). In a second study designed to evaluate the possible therapeutic use of the new drug, 0.3 or 0.6 mg cabergoline was administered orally once weekly for 9 weeks to 2 groups of 15 and 16 hyperprolactinemic patients, respectively. Serum PRL levels fell significantly by the first week and reached a plateau after 2 doses in the 0.6 mg cabergoline-treated group and after 5 doses in the 0.3 mg-treated group; the absolute PRL decrease was greater in the former. Ten patients in each group achieved normal serum PRL levels, and a marked decrease (greater than 50% of pretreatment values) occurred in all patients treated with 0.6 mg and in 13 treated with 0.3 mg weekly. Resumption of menses occurred during the treatment period in 15 of the 17 premenopausal women with amenorrhea. Six patients who had poor responses had better responses when given higher drug doses for 4 weeks, and serum PRL levels became normal in the 3 receiving 0.6 mg twice weekly. These data confirm that cabergoline is a long-acting oral dopaminergic drug and suggest that it may be a useful agent for the treatment of patients with hyperprolactinemia.

Adolescent

Detection of cell surface antigens in tissue sections by means of pre-embedding immunogold staining.

The immunogold technique has been used in electron microscopy to detect cytoplasmic and extracellular antigens by postembedding techniques. It has also been used to detect plasma-membrane-associated molecules on suspended cells and, recently, to visualize cell surface antigens in ultrathin sections of Lowicryl embedded specimens. In the present study, cell surface antigens of rat kidney and human skin were identified in tissue sections by using pre-embedding immunogold labeling. Brush border microvillar antigens and dermal lymphocyte antigens both bound numerous gold particles. The immunogold staining described here has the advantage over immunoperoxidase procedures that is not subject to diffusion or reabsorption artifacts, and allows estimation of the antigen density on labeled cells. Furthermore, this pre-embedding immunogold technique is ideally suited to detecting cell surface-associated antigens since it preserves antigenicity, allows gold particle penetration and enhances cell membrane profiles.

Animals

Compensatory changes in calcium uptake and phospholipid composition in rat renal brush border membranes after unilateral nephrectomy.

Unilateral nephrectomy (uNX) induces a decrease in calcium uptake by brush border membranes (BBM) in the remnant kidney compared to control membranes. This effect was found to occur within 48 h and persisted at 2 weeks after uNX. Moreover, this decreased calcium uptake appears to occur through a diminished binding capacity of the BBM. Our studies also show that renal hypertrophy induced a specific decrease in the content of acidic phospholipids in remnant kidney BBM by 48 h after uNX. The decrease in phosphatidylinositol 4,5-bisphosphate and phosphatidic acid was transitory but phosphatidylinositol 4-monophosphate levels remained lower in the BBM at 2 weeks after uNX compared to control membranes. These results suggest that the decreased calcium uptake by remnant kidney BBM after uNX is related to a decreased membrane content of acidic phospholipids. This effect might account, at least in part, for the decrease in fractional calcium reabsorption during renal compensatory hypertrophy.

Animals

Regulation of endometrial transglutaminase activity during the menstrual cycle.

When human endometrial transglutaminase was measured a 10-fold higher activity was detected during the secretive phase. This change was not related to either differences in solubility of the enzyme or to selective contamination by plasma factor XIII and rather appears to depend on the expression of the tissue form of transglutaminase, suggesting that this enzyme is regulated in vivo by progesterone.

Endometrium