Search

Membranous glomerulonephritis is the most common glomerular disease associated with malignancy, the association of minimal change glomerulopathy with solid tumor is still uncommon. We report a 72-year-old man with nephrotic syndrome due to minimal change glomerular disease; an accurate seek of underlying malignancy revealed a cecum adenocarcinoma. We had a complete remission of nephrotic syndrome after surgery of carcinoma.

Stimulation by platelet-derived growth factor (PDGF) is known to increase the number of IGF-I binding sites in cells in culture. We show here that PDGF also increases the levels of IGF-1 receptor mRNA. Using cell lines stably transfected with an expression plasmid in which the reporter luciferase gene is under the control of the rat IGF-1 receptor gene promoter, we find that PDGF increases the activity of this promoter. A short IGF-1 receptor gene promoter, comprising about 100 base pairs of the sequence immediately upstream of the initiation of transcription site, is sufficient for a response to the stimulatory action of PDGF. These results suggest that an increase in RNA levels and in promoter activity may play an important role in the increase in IGF-1 receptor levels that occurs after stimulation by PDGF.

It is known that anti-HLA Class I antibodies inhibit the proliferative response of PHA-activated T-lymphocytes. We found that plastic- or sepharose-linked anti-HLA Class I monoclonal antibody 01.65 does not inhibit either [3H]Thymidine incorporation or recruitment in the cell cycle, nor does it reduce the expression of c-myc mRNA and the membrane expression of Interleukin-2 Receptor and Transferrin Receptor. Furthermore, particulate Protein Kinase C is not affected by anchored anti-HLA Class I monoclonal antibody 01.65. We suggest that anti-HLA Class I monoclonal antibody may act through crosslinking or internalization of HLA Class I antigens.

We identified a subgroup of ataxia-telangiectasia (AT) patients (2 sibs and 1 unrelated case) characterized by typical clinical manifestations of the disease and cellular radiosensitivity intermediate between classical AT and normal subjects. Our data and a literature review of the intermediate radiosensitivity AT cases show that radioresistant DNA synthesis, cellular radiosensitivity (measured in terms of survival and chromosome breakage), and the clinical hallmarks behave independently. This raises a number of interesting questions about the correlation between radiobiological and clinical features, and about the nature of the AT gene(s).

HLA class I antigens seem to be involved in the proliferative response of PHA-activated human T-lymphocytes. We have previously reported that the treatment of PHA-activated peripheral blood mononuclear cells (PBMC) with an anti-HLA class I monoclonal antibody, 01.65, (i) inhibits the tritiated thymidine incorporation, (ii) inactivates cytosolic protein kinase C (PKC) and (iii) causes an increase in the duration of the cell cycle. Northern Blot kinetic analysis of c-fos, c-myc, cdc2, IL-2R, c-myb, ODC, TK and H3, from 10 minutes to 120 hours, was performed in MAb 01.65 treated cultures. We found that the expression of four genes (c-myc, IL-2R, cdc2 and TK) was depressed 24 hours after PHA stimulation.

N-N-Staurosporine (STAR) inhibits in a dose dependent manner Tritiated-Thymidine (3H-TdR) incorporation in phytohemagglutinin (PHA) activated Peripheral Blood Mononuclear Cells (PBMC) treated with anti-HLA class I monoclonal antibody (MAb) 01.65 and its effect results competitive with MAb 01.65. Cytosolic and particulate Protein Kinase C (PKC) have been studied. Only when PKC particulate activity is no more detectable, the effect of STAR on 3H-TdR incorporation is evident.

Monoclonal anti HLA class I antibodies inhibit the proliferative response of PHA-stimulated T lymphocytes. We studied the effects of MAb 01.65 anti-HLA class I on c-fos, c-myc and IL-2R mRNA expression. We found that MAb treatment does not modify either c-fos mRNA levels observed after 10 minutes to 3 hrs or the early c-myc mRNA expression revealed after 1 to 6 hrs, but decreases the intensity of autoradiographic signals of late c-myc and IL-2R mRNA expression. Since we had previously ascertained that MAb 01.65 treatment induces a decrease in PKC enzymatic activity after few minutes, the correlation of that result with the data presented in this paper will be discussed.

Cytosolic and Particulate Protein Kinase C has been studied in Peripheral Blood Mononuclear Cells activated with 12-O-Tetradecanoyl phorbol 13-acetate and treated with the anti-HLA Class I Monoclonal Antibody 01.65. No effects on the cellular distribution of PKC activity nor to the proliferative response has been found. In phytohemagglutinin stimulated PBMC cultures treated with MoAb 01.65 total PKC activity depletion and 3H-Thymidine incorporation inhibition has been found. In PBMC cultures activated with both PHA and TPA, the proliferative response was similar to cultures activated with PHA alone, while the PKC cellular distribution was similar to the one detected in TPA stimulated cultures. Addition of the MoAb 01.65 was ineffective on both PKC activity and 3H-Thymidine incorporation. These data indicate that anti-HLA Class I MoAb induced 3H-Thymidine incorporation inhibition may be related to low levels of PKC activity.

The monomorphic anti-HLA Class I monoclonal antibody 01.65 inhibits the incorporation of tritiated thymidine ([3H]TdR) in Phytohemagglutinin (PHA)-activated human T lymphocytes. Our data indicate that 01.65 affects the average duration of the cell cycle by increasing the length of the early S subphase. As a consequence of the increase in the doubling time of the cell population, the absolute number of cells at harvesting time was reduced in 01.65-treated cultures compared to that of untreated cultures. The lengthening of the S-phase and the decrease in the cell number can together quantitatively account for the reduction of [3H]TdR incorporation observed in 01.65-treated cultures.

Anti HLA Class I Monoclonal Antibody depletes Protein Kinase C (PKC) to 20% of control value in PHA activated human T cells. The effect is reversible: in 24 hours the enzymatic activity returns to 58% of control value. Removal of antibody from the culture medium increases the rate of recovery. Implications of this finding for the modulation by HLA Class I antigens of the proliferative response of T cells to lectins are discussed.

Two unrelated patients carrying imbalances involving the long arm of chromosome 6 are described. In the first trisomy 6q21 leads to qter had segregated from a maternal translocation t(6;16)(q15;q24). The clinical data of the proposita are compared with those of three other published cases. A partial 6q trisomy syndrome is postulated characterized by: growth deficiency of prenatal onset, psychomotor retardation, craniofacial abnormalities (microcephalia, hypertelorism, downward slanting palpebral fissures, flattened nasal bridge, long philtrum, hypoplastic perioral features, large jaw resulting in a round appearance of the face, receding chin, malformed ears) and dysmorphic extremities (contractures of limbs due to short flexor tendons, hypoplastic fingers, toes and nails). In the second case, monosomy 6q221 leads to qter resulted from a de novo rearrangement and was responsible for mental retardation and facial dysmorphism (reduced biparietal diameter, hypotelorism, absent eyebrows, prominent nose, ptosis, receding chin, dysmorphic ears). Studies of HLA and PGM3 segregation showed normal inheritance patterns and ruled out the location of these genes in bands 6q221 leads to qter.

One hundred and twenty-one Italian children with coeliac disease (CD) have been compared with a control population from the same geographical area for the distribution of HLA-DR and DQ antigens. The pattern of an increase in DR3, DR7, and of heterozygotes DR5/7 was associated with an excess of heterozygotes DQw2/DQw3 in the CD population. These findings suggest that epitopes determined by specific combinations of DQ alpha and beta chains (combinatorial determinants) predispose to the disease.

The hybridoma technique was used to produce a mouse monoclonal antibody, designated as XI 21.4, which belongs to the IgG2a class. It is active in complement-dependent cytotoxicity and detects a B-cell antigenic determinant associated with DR1, DR4, DRw10, and, possibly, DRw9. Microfingerprinting of the immunoprecipitate from a homozygous DR4 cell line shows a typical alpha DR pattern and a beta pattern coinciding with that of DR4 molecules.

A case of partial trisomy 9 is described in a mentally retarded and dysmorphic child, confirming that this chromosome unbalance results in a characteristic clinical entity. This trisomy arose through aberrant segregation of translocation chromosome during meiosis in the patient's mother, who is a balanced heterozygote for a complex translocation involving chromosomes 9, 21 and 22. The phenotypically normal sister of the proposition is also carrier of the same complex translocation.

Centric fission of chromosome No. 4 was found in the healthy mother of two children with trisomy 4p. The two telocentrics derived are stable and show no evidence of fusing again. The 2:3 ratio of unbalanced offsprings born to the proposita indicates that, contrary to the evidence emerging from studies in other species, the risk for the production of unbalanced gametes is high.

A mouse-human hybridoma has been produced by fusing human splenocytes from a Cooley's anemia patient with the murine myeloma P3-NS1/1-Ag 4-1. The hybridoma is stable after 18 months and secretes human IgM. The antibody reacts with some H3N2 influenza A strains and detects an epitope that is part of the hemagglutinin antigen, but does not affect virus infectivity.

Owing to our current interest in synthesizing and evaluating the antiulcer and antisecretory activity of bicyclic compounds, a series of 1(or 3),4,6,7-tetrahydropyrano- and 1(or 3),4,6,7-tetrahydrothiopyrano-[3,4-d]imidazoles was synthesized and tested. The biological results were compared with those of some previously described 4,5,6,7-tetrahydroimidazo-[4,5-c]pyridine and 4,5,6,7-tetrahydrobenzimidazole derivatives.