Adenocarcinoma of stomach: changing concepts in pathogenesis and therapy.
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Adenocarcinoma↗
Biomedical subjects
M Stefanini
Publications and source records attributed to M Stefanini.
Blood and bone marrow eosinophilia in malignant tumors. Role and nature of blood and tissue eosinophil colony-stimulating factor(s) in two patients.
Eosinophilia of the blood and bone marrow may be encountered in patients with disseminated malignancies. It is unrelated to the histologic type of the tumor but usually reflects its aggressiveness and prognostic outlook. Its pathogenesis is controversial. The presence of eosinophil colony-stimulating factor(s) in serum and malignant tissue extracts was evaluated in two cases of malignancies accompanied by marked blood and bone marrow eosinophilia. When compared with controls, serum and tumor tissue extracts stimulated the growth of G, M, and Eo colonies in semisolid cultures of human bone marrow. Such stimulating effect was inhibited by the addition of antibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3. Thus, the colony-stimulating factor(s) play a role in the pathogenesis of the eosinophilia associated with some malignant tumors, and these factors appear to include GM-CSF, interleukin-3, and probably others.
Adenocarcinoma↗
Novel Chinese hamster ultraviolet-sensitive mutants for excision repair form complementation groups 9 and 10.
In this paper we demonstrate that the mutants CHO7PV and CHO4PV isolated by us from the CHO-K1 prol- cell line represent two new complementation groups of UV-sensitive excision repair-defective rodent mutants. We have classified the mutant CHO7PV as representative of Group 9 and CHO4PV as representative of Group 10. Cellular and biochemical characterization of these mutants indicates that they are moderately sensitive to a broad spectrum of mutagens (UV and mono- and bifunctional alkylating agents), partially unable to perform UV-induced DNA repair synthesis, and partially defective in the incision step of the DNA excision repair pathway and in the removal of the two main lesions caused by UV [cyclobutane pyrimidine dimers and (6-4) photo-products]. In terms of UV survival and incision, CHO4PV is apparently more defective than CHO7PV (40% and 50% of wild-type survival, respectively, and 55% and 75% of wild-type incision), whereas when repair DNA synthesis and lesion removal are compared, CHO7PV seems to be more severely affected (30% of wild-type unscheduled DNA synthesis in CHO7PV and 60% in CHO4PV). This suggests a subtlety in the relation between removal of these specific lesions and overall repair capacity and survival.
Animals↗
In vitro production of estradiol by ovarian granulosa cells in a case of McCune-Albright syndrome.
A 14-year-old girl presented with classic McCune-Albright syndrome. She underwent the ablation of several cysts during a laparotomy performed on the basis of persistent and intense pelvic pain and recurrent episodes of menometrorrhagia not responsive to pharmacologic therapy. Granulosa cells obtained from an isolated follicle and a cyst were cultured and estradiol (E2) secreted in the culture medium measured. Granulosa cells, obtained from the follicle, produced much higher levels of estradiol compared to those of cells coming both from follicles of equivalent size and preovulatory follicles of normal patients. Secretion of E2 by granulosa cells from the cyst was comparable to that of normal preovulatory follicles. We conclude that in this patient, ovaries are hyperfunctioning in terms of E2 production. This high production of estradiol and the fact that several cysts were found in the ovaries can justify the high levels of estradiol found in the serum of this patient at the moment of the operation.
Adolescent↗
Chromosome rearrangements in normal fibroblasts from xeroderma pigmentosum homozygotes and heterozygotes.
Chromosome analysis was carried out in cultured fibroblasts from unaffected skin of five unrelated xeroderma pigmentosum (XP) patients and nine family members. Structural chromosome changes were observed in cultures from all examined individuals. Furthermore, in one XPD patient and in one XPC patient and his parents, cytogenetically abnormal clones were detected. Some of these clones were present starting from the primary explant. This cytogenetic pattern is similar to that observed in an XPC patient previously studied by us. The analysis of breakpoint distribution from clonal and non-clonal chromosome rearrangements showed that some breakpoints were more frequent and common to different families or to different family members although definite evidence of preferential involvement of chromosome bands was not obtained. This investigation indicates that there is a consistent tendency toward chromosome instability in XP mutation carriers. The instability could be related to the multiple chromosome anomalies characterizing skin tumors in XP subjects.
Adolescent↗
Xeroderma pigmentosum complementation group H falls into complementation group D.
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Autoradiography↗
An intercellular adhesion protein of rat testis: isolation and preliminary characterization.
By using biochemical and immunochemical approaches, we have isolated a rat spermatocyte surface protein of an apparent molecular weight of 80 kd involved in spermatocyte-Sertoli cell recognition in culture. Preliminary characterization of such a molecule has demonstrated that 1) it is a nonintegral membrane component; 2) it possesses a small amount of N-linked oligosaccharides of the high mannose type; and c) it is a stage-specific molecule, being present only in middle-late pachytene spermatocytes.
Animals↗
Safe and effective, prolonged administration of epsilon aminocaproic acid in bleeding from the urinary tract.
A total of 9 patients with macroscopic hematuria from various causes, none with evidence of disseminated intravascular coagulation, received low oral, divided doses (approximately 150 mg. per kg. per day) of epsilon aminocaproic acid for up to 21 consecutive days. The hematuria was controlled effectively without overt clinical reactions. Parameters of hepatic and renal function, indicators of muscular damage, were studied in detail in 3 patients. No significant abnormalities were found. The use of small doses of epsilon aminocaproic acid was not accompanied by significant complications and appeared to be effective in special situations for the control of urinary bleeding. This therapy may have indications in a number of urological states accompanied by excessive hematuria.
Adult↗
Search for consanguinity within and among families of patients with trichothiodystrophy associated with xeroderma pigmentosum.
The association of two rare hereditary disorders, trichothiodystrophy (TTD) and xeroderma pigmentosum (XP), was found in four patients from three families, apparently unrelated but living in the same geographical area. In order to test the hypothesis of a common ancestor, consanguinity within and among the families was checked using three different approaches: reconstruction of genealogical trees, typing of blood markers, and surname analysis. The results of the three types of analyses strengthen the hypothesis that, in at least two out of the three families, the genetic defect determining the TTD/XP phenotype is identical by descent, as a consequence of remote inbreeding. This implies that if two mutations are responsible for the two diseases they are at linked loci or affect the same gene.
Blood Group Antigens↗
Idiopathic thrombocytopenic purpura (ITP): an analysis of 1,122 cases. "Allergic" versus "autoimmune" forms.
Clinical findings, course, complications, outcome, response to treatment and possible pathogenetic mechanisms were evaluated in 1,122 cases of idiopathic (immunological) thrombocytopenic purpura seen over a period of 30 years. Evaluation of clinical and laboratory findings suggests that there are at least two types of idiopathic thrombocytopenic purpura. One, "allergic," is acute in onset, often related to exposure to viral or bacterial infections, is associated with more severe bleeding manifestations in the early stages, is in most cases self-limited, and responds favorably to corticosteroids in the event of very severe bleeding. Antiplatelet factors disappear upon achieving a clinical and hematological remission. The other, "autoimmune," has slow onset of symptoms, chronic course, may respond to corticosteroids and/or immunosuppressive drugs and more often to splenectomy, and is refractory to all therapy in a significant number of cases. Antiplatelet factors remain present even after clinical remission. Both forms are relatively benign processes. However, autoimmune (chronic) cases may show serious hemorrhagic complications and evolve into other autoimmune syndromes and malignant processes.
Acute Disease↗
Modulation of phagocytic activity in cultured Sertoli cells.
Phagocytic activity of rat Sertoli cells that were cultured in vitro has been evaluated as the ability to internalize polystyrene beads. Our data demonstrate that these cells are active phagocytes and that such phagocytic activity is under negative control by follicle-stimulating hormone (FSH). The hormonal control is mediated by increased intracellular levels of cAMP. Moreover Sertoli cell responds to tuftsin, an oligopeptide known to act only on macrophages and granulocytes, by increasing up to five times its phagocytic activity. Phagocytic uptake of polystyrene beads is associated with dramatic changes of the cellular shape. Such morphological modifications are significantly reduced under FSH stimulation. The physiological implications of the data are discussed.
Animals↗
Signal transduction in the Sertoli cell: serum modulation of the response to FSH.
Immature Sertoli cells of the testicular seminiferous tubule maintain the expression of their differentiated phenotype when cultured in unsupplemented medium. In preliminary experiments we observed that foetal bovine serum (FBS) stimulates polyphosphoinositides (PI) hydrolysis in Sertoli cells. We then evaluated the effect of serum on the function of the immature Sertoli cell in culture, in terms of cAMP and estrogen production. Treatment of Sertoli cells for 30 min with 1-10% FBS had no effect on basal cAMP accumulation but abolished the response to FSH. The serum concentration producing half-maximal inhibition of the FSH-dependent cAMP accumulation was 0.5-1%. Comparison of the FSH-dose-response in the absence or presence of serum showed a decreased maximal response when serum was present. Sertoli cells exposed to serum were also less responsive to the beta-adrenergic agonist isoproterenol, to cholera toxin, and to forskolin. The serum inhibition was rapidly reversed upon removal of serum or incubating the cells with the phosphodiesterase inhibitor MIX (methyl-isobutyl-xanthine). Similarly to what observed with cAMP, serum affected androgen aromatization stimulated by FSH, isoproterenol, cholera toxin, forskolin and dibutyryl cAMP. These data indicate that factors present in serum can act as modulators of the Sertoli cell function in vitro by rapidly and reversibly inhibiting the cAMP and steroidogenic response of the Sertoli cell to FSH.
Animals↗
Clonal chromosome rearrangements in a fibroblast strain from a patient affected by xeroderma pigmentosum (complementation group C).
We report the results of DNA repair studies and cytogenetic investigations in a patient presenting acute phothosensitivity and cancerous skin lesions. In lymphocytes and fibroblasts a reduced level of unscheduled DNA synthesis after UV irradiation was found and the presence of xeroderma pigmentosum, complementation group C, mutation was demonstrated by complementation analysis. In lymphocyte and fibroblast cultures the frequency of spontaneous chromosome gaps and breaks was normal, whereas the frequency of chromosome rearrangements was higher than expected. In fibroblasts from the 4th to the 18th passage of the culture, 4 reciprocal translocations with a clonal distribution were identified. The rearranged chromosomes were Nos. 2, 13, 14 and 15, Nos. 2 and 13 being both involved in 3 different translocations with breakpoints at 2q21, 2q31, 2p23 and 13q31, 13q12 or 3. The biological significance of this finding is discussed in view of a possible correlation with the DNA repair defect and a possible relevance in tumor development of specific chromosome rearrangements.
Adult↗
Chromosome instability in lymphocytes from a patient with Werner's syndrome is not associated with DNA repair defects.
Different cellular parameters used to detect genetic instability were analyzed in lymphocytes from a patient affected by Werner's syndrome (WS). Cytogenetic studies indicated the presence of structural and numerical chromosomal abnormalities and the occurrence of variegated translocation mosaicism. The baseline mutation frequency was similar to that observed in normal donor samples. DNA repair investigations showing a normal capability to perform UV-induced DNA repair synthesis and a normal sensitivity to various mutagens (UVC light, mono- and bi-functional alkylating agents) indicate that different DNA repair mechanisms act normally in WS. In this feature, WS appears to differ from the other genetically determined syndromes in which chromosomal instability is associated with a marked hypersensitivity to specific DNA-damaging agents.
Cells, Cultured↗
Spectrin, fodrin and protein 4.1-like proteins in differentiating rat germ cells.
The presence and the distribution of proteins of the membrane skeleton in differentiating germ cells of the rat has been investigated. Immunofluorescence and immunoblotting analysis, performed using monoclonal and polyclonal antibodies to human erythroid alpha-spectrin and protein 4.1 and to brain spectrin (fodrin), demonstrated the presence of analogues of spectrin and fodrin in spermatocytes and round spermatids and of protein 4.1-like molecules in spermatocytes, spermatids and spermatozoa. Spectrin and fodrin showed molecular weights comparable to those of their analogues in erythrocytes but a distinct intracellular distribution. Fodrin was localized along the plasma membrane while spectrin appeared associated with the regions of the Golgi apparatus and of the developing acrosome. Antibodies to protein 4.1 recognized molecules with a molecular weight not comparable with that in erythrocytes, and their presence in spermatozoa was confined to specific regions of the head and of the tail.
Animals↗
Cellular and genetic characterization of UV sensitive Chinese hamster mutants.
Results of cellular and genetic characterization of UV sensitive clones (UVs) isolated from CHO-K1 cell line are reported. The cross-sensitivity to agents inducing a variety of DNA lesions, the induction of chromosome aberrations and of 6-thioguanine and ouabain resistant mutants, the occurrence of methotrexate resistant cells were analyzed in clones showing different degrees of UV sensitivity. Genetic analysis was performed by complementation analysis of hybrids obtained by fusion of our mutants with UVs cells belonging to the six complementation groups (c.g.) so far identified. Three clones were assigned to c.g. 2, one clone to c.g. 5. Two clones (CHO7PV and CHO4PV), were able to complement each other and showed complementation after fusion with any of the six c.g.; these clones were considered carriers of two new mutations in genes presumably involved in DNA repair.
Animals↗
Distribution of analogues of spectrin, fodrin and protein 4.1 in rat spermatogenic cells.
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Animals↗
Monitoring of genetic instability in subjects with increased risk of cancer.
Results of investigations performed to obtain data on genomic instability in subjects with increased risk of cancer are reported. People at risk for environmental or genetic factors included in this study were: 1) individuals from the Seveso population exposed to dioxin; 2) psoriatic patients exposed to photochemotherapy; 3) members of a family with a high incidence of colonic cancer; 4) patients affected by nevoid basal cell carcinoma syndrome; 5) patients with photosensitivity. The following cellular parameters were analyzed in peripheral blood lymphocytes: (i) frequency of chromosome aberrations and of sister chromatid exchanges; ii) sensitivity to different DNA damaging agents; iii) efficiency of DNA repair after UV irradiation and iv) frequency of spontaneous mutations.
Chromosome Aberrations↗