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Biomedical subjects

M Giordano

Publications and source records attributed to M Giordano.

At least 163 records · Page 9Linked to original sources

The relationship between body composition and plasma concentrations of exogenously administered urinary follicle stimulating hormone.

The aim of this study was to evaluate the plasma absorption of i.m. administered exogenous urinary follicle stimulating hormone (FSH) in relation to body fatness, leanness and cell mass. Body composition was measured by means of bioelectrical impedance. An immunoradiometric assay was used to assess the concentration of exogenous FSH in blood in patients with a pharmacologically induced hypogonadotrophism who were undergoing ovulation induction for assisted reproduction. No correlation was found between body composition and the hormone concentration in blood. According to our results, the different requirements of gonadotrophin administration typically observed in patients of different weights are probably not related to different absorption and distribution of the drug.

Adult↗

Seasonal variations in antibody-dependent cellular cytotoxicity regulation by melatonin.

Data collected over a period of 4 years show that melatonin (two daily i.v. injections of 0.1 mg/kg body wt. given at 16:00 h) was able to enhance antibody-dependent cellular cytotoxicity (ADCC) in summer, but not in winter. Dose-response curves carried out in January, May, July, and October suggest that the seasonal effects reported are related to differences in the sensitivity of mice to melatonin during the course of the year. These results show seasonal variations in the immune modulatory action of melatonin.

Animals↗

Gametic association of HSP70-1 promoter region alleles and their inclusion in extended HLA haplotypes.

Gametic associations of a three-allele polymorphism of the HSP70-1 promoter region were analyzed in a random North Italian population, in 69 HLA homozygous cell lines and in 29 families in Boston, all typed for HLA class I, class II and complement alleles. Significant phenotypic associations were detected in the random population between HSP70-1 alleles and several HLA markers carried by extended haplotypes. The inclusion of HSP70-1 alleles in extended haplotypes, suggested by population analysis, was confirmed in genotyped cells, including 10W HLA homozygous cell lines and families, selected for the presence of the whole set of alleles reported for conserved extended haplotypes. Every tested extended haplotype was exclusively associated with a given HSP70-1 allele, except those carrying DR1. HSP70-1 C was included in both [HLA-B8, SC01, DR3] and [HLA-B18, F1C30, DR3] extended haplotypes, accounting for the previously observed strong association with DR3. In addition the same allele was found on the [HLA-B13, SC31, DR7], on the [HLA-B62, SB42, DR4] and on the [HLA-B60, SC02, DR13] extended haplotypes. The HSP70-1 A allele was carried by all DR4+ extended haplotypes except the one above cited. HSP70-1 B correlated with DR10, DQB1*0501 and BF*F. Thus the HSP70-1 promoter alleles provide new precisely located markers of extended haplotypes.

Alleles↗

Pulmonary arterial hypertension responsive to immunosuppressive therapy in systemic lupus erythematosus.

Two female patients with recent diagnosis of systemic lupus erythematosus (SLE) are reported. Pulmonary arterial hypertension was diagnosed by Doppler echocardiography. Immunosuppressive therapy was started at the time of diagnosis of SLE. After 2 months of therapy, Doppler echocardiography was repeated and the estimated pulmonary artery systolic pressure was substantially decreased from 78 to 42 mmHg and from 67 to 42 mmHg, respectively, along with significant improvement of the clinical conditions.

Adult↗

Promoter for the human ferritin heavy chain-encoding gene (FERH): structural and functional characterization.

We conducted a functional analysis of the promoter for the human ferritin heavy chain-encoding gene (pFERH) in HepG2 and HeLa cells. The activity of pFERH is equivalent in both cell types, despite their different ferritin (Fer) isotypes. Transfections of a series of 5'-deletion mutants indicate that pFERH activity is essentially dependent on two motifs. One of them, accounting for about 50% of the total transcriptional activity, is recognized by the RNA polymerase II transcription factor, Sp1, and the other by a low-affinity factor present in both the cell types analyzed.

Base Sequence↗

Flow cytometric analysis of multidrug-resistance-associated antigen (P-glycoprotein) and DNA ploidy in human colon cancer.

In many cell systems, resistance to cytotoxic drugs is acquired by the amplification and/or overexpression of the multidrug resistance (mdr) gene, which codes for the glycoprotein, p170 (P-glycoprotein). Moreover, in a variety of malignant tumours there is increasing evidence of the relationship between the DNA ploidy pattern of patients and their prognosis. In this study we aimed to evaluate these two potential indicators of constitutive drug resistance in human colorectal tumours. We employed a method to quantify simultaneously, on a per cell basis, mdr gene expression (using the C219 monoclonal antibody for P-glycoprotein) and nuclear DNA content with high-resolution bivariate flow cytometry. The study was performed on a human colon-carcinoma-derived cell line (LoVo) and its doxorubicin-resistant variant (LoVo/Dx) and on tumour samples and adjacent normal mucosa from 35 untreated patients with colon cancer. The P-glycoprotein was found in both LoVo and LoVo/Dx cells with levels slightly lower in the parental than in the resistant subline (P, NS). A multi-drug-resistant specific probe for mRNA expression and Western blot assay confirmed the specificity of p170 expression. All of the colon cancer with unimodal diploid DNA distribution and all the normal colonic mucosa samples showed P-glycoprotein expression, without a statistically significant difference in median values between tumours and normal samples. Tumours with bimodal DNA distribution showed median values of P-glycoprotein expression of their hyperdiploid cell clones significantly higher than those of their diploid clones and of the tumours with unimodal DNA distribution (P less than 0.005). Our results show the feasibility of bivariate flow-cytometric analysis of P-glycoprotein expression and DNA content on clinical material and support the hypothesis that the MDR phenotype and DNA ploidy together may influence the biological behaviour of colon cancer in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Glucose and amino acid metabolism in chronic renal failure: effect of insulin and amino acids.

The effects of hyperinsulinemia and hyperaminoacidemia on glucose and amino acid metabolism were examined in 16 control and 13 chronic renal failure (CRF) patients under two conditions: 1) euglycemic hyperinsulinemia and 2) amino acid infusion. All studies were performed with continuous indirect calorimetry and [1-14C]leucine infusion. In CRF patients insulin-mediated whole body glucose metabolism was reduced by 35% (4.41 +/- 0.50 vs. 6.76 +/- 0.73 mg.kg-1.min-1, P less than 0.01), primarily due to a decrease in nonoxidative glucose disposal (1.70 +/- 0.70 vs. 4.32 +/- 0.60 mg.kg-1.min-1, P less than 0.01); glucose oxidation was similar in both groups. In the postabsorptive state total leucine turnover (1.56 +/- 0.06 vs. 1.75 +/- 0.06), leucine oxidation (0.25 +/- 0.01 vs. 0.30 +/- 0.01), and nonoxidative leucine disposal (1.29 +/- 0.06 vs. 1.40 +/- 0.07 mumol.kg-1.min-1) were reduced in CRF vs. control subjects (all P less than 0.05). In response to hyperinsulinemia, endogenous leucine flux (index of proteolysis), leucine oxidation, nonoxidative leucine disposal (NOLD) (index of protein synthesis), and net leucine flux into protein were similar in CRF and control subjects. In contrast, the ability of hyperaminoacidemia to enhance NOLD (1.54 +/- 0.11 vs. 2.10 +/- 0.10 mumol.kg-1.min-1, P less than 0.01) and net leucine balance (0.27 +/- 0.05 vs. 0.41 +/- 0.05, P less than 0.05) was reduced in CRF patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

HER-2/neu oncogene expression and DNA ploidy in normal human kidney and renal cell carcinoma.

Using flow cytometry (FCM), we have investigated both the DNA content (stained with propidium iodide) and HER-2/neu oncogene expression (revealed by means of an anti-HER-2/neu monoclonal antibody) in neoplastic and non-neoplastic kidney samples from 20 patients with renal cell carcinoma. All the non-neoplastic samples and 15/20 (75%) renal cell cancers showed diploid modal DNA content while the remaining 5 neoplastic sample (25%) showed both diploid and hyperdiploid cell populations. In normal kidney the level of HER-2/neu oncoprotein was low (median fluorescence values in arbitrary units = 7.5 AU, range: 4-10 AU). In diploid renal cancers the level of HER-2/neu was slightly increased (median fluorescence values = 20 AU, range: 9.5-30 AU) (p < .005). The relationship of HER-2/neu expression to the cell cycle in these tumor samples is not clear since most of the cells express the antigen in all phases of the cell cycle. On the other hand, there is an association between HER-2/neu expression and abnormal DNA content suggesting that aneuploid pattern may be biologically related to overexpression of the HER-2/neu gene.

Aneuploidy↗

[Ventricular late potentials in hypertrophic cardiomyopathy: personal contribution and analysis of the literature].

BACKGROUND: Patients with hypertrophic cardiomyopathy are at increased risk of sudden death. Recently it has been investigated whether late potentials can be useful markers of that risk in such patients, with discordant results. The aim of our study was to detect a correlation, if any, between late potentials, ventricular tachycardia and the hypertrophy extension. METHODS: Twenty-five patients were enrolled, 19 males and 6 females, mean age 40.40 +/- 15.02 years. Each underwent 24h Holter monitoring, averaged ECG, M-Mode and 2-D Echo. The hypertrophy was considered extensive (septum and free wall) or non extensive (septum and/or apex). RESULTS: Late potentials of a mean duration of 37 +/- 14.83 ms were recorded in 5/7 patients with documented ventricular tachycardia vs in none of the non tachycardia group. Sensibility was 100%, specificity 71% and predictive value 100%. Late potentials were present in 8.3% of patients with non extensive and in 30.8% of patients with extensive hypertrophy (p = NS). CONCLUSIONS: From our data it seems that extensive hypertrophy is present in about half of patients with hypertrophic cardiomyopathy, and this roughly correlates with a more frequent ventricular tachycardia and with late potentials. Furthermore, late potentials are strictly related to the incidence of ventricular tachycardia in this disease, just as in ischemic heart disease or in idiopathic dilated cardiomyopathy. The small number of our cases may not be sufficient to reach a significant statistical correlation between late potentials and hypertrophy, but we believe that the trend is very promising.

Action Potentials↗

Argyrophil-negative G-cell duodenal carcinoid.

A case of mono-hormonal-producing and functionally active G-cell carcinoid tumor of the duodenum is described. The tumor, found to be argyrophil negative, was investigated immunohistochemically and ultrastructurally. We report our results, then discuss the possible histochemical causes that can lead to the failure of argyrophilia, and direct attention to the possible misdiagnosis that can result from that failure.

Carcinoid Tumor↗

Purification and properties of a novel DNA methyltransferase from cultured rice cells.

DNA methyltransferase activity has been observed in a total crude homogenate of rice cells grown in suspension culture using either native plant DNA or, under the conditions used, the more responsive hemimethylated poly (dI-MedC).poly(dI-dC). Using the latter substrate we have purified an enzyme fraction 380-fold by salt extraction of chromatin, DEAE cellulose and phosphocellulose. This purified fraction showed enzyme activity only with poly (dI-MedC).poly(dI-dC) thus suggesting the occurrence in plants of a DNA methyltransferase specific for hemimethylated DNA. A Mr value of 54000 was calculated on the basis of the sedimentation coefficient which was determined by sucrose density gradient centrifugation. Apparent Km values for poly (dI-MedC).poly(dI-dC) and S-adenosyl-L-methionine were found to be 17 micrograms/ml and 2.6 microM, respectively.

Cells, Cultured↗

Hypoechoic lesions in fatty liver. Quantitative study by histomorphometry.

Ten patients with fatty liver changes were subjected to liver biopsies. In seven, ultrasonography showed focal hypoechogenicity within a "bright" liver, generally interpreted as focal sparing. Three patients had hyperechoic areas surrounded by "normal" parenchyma usually felt to represent local fat accumulation without diffuse involvement. Morphometric analysis was used to determine the total area occupied by fat (area density) and the number of lipid droplets (numerical density) per microscopic field in lesional and perilesional specimens. Compared with respective perilesional values, hypoechoic lesional numerical densities were significantly lower in 6 of 7 patients; the three hyperechoic samples had significantly higher values. In most cases, lesional and perilesional area densities were not significantly different. These hypoechoic focal lesions are believed to be merely areas in which a similar quantity of fat is contained in fewer droplets, and focal hyperechogenicity is believed to result from a larger number of fat-filled vacuoles with respect to that of the surrounding parenchyma. Variation in the number of solid-liquid interfaces causes the ultrasonic contrast between these lesions and the similarity fatty liver parenchyma surrounding them.

Biopsy, Needle↗

Effect of cyclophosphamide on the clearance of IgG-sensitized red cells in mice.

The effects of cyclophosphamide (Cy) on the clearance of IgG-sensitized erythrocytes (EA) were examined. The results clearly indicate that Cy treatment enhances the capacity of the mononuclear phagocytic system to remove antibody-coated cells from the circulation in normal and decomplemented mice. The enhanced rate of clearance is the consequence of an increased uptake of EA by the liver and spleen. We explored the possibility that the enhancement of Fc receptor-mediated clearance might be an important effect to be taken into account in the search for a more effective therapy of immune complexes diseases.

Animals↗

Proliferating cell nuclear antigen (PCNA)/cyclin expression during the cell cycle in normal and leukemic cells.

Bivariate flow cytometric analysis of the cell proliferation-associated nuclear protein, identified as the "proliferating cell nuclear antigen" (PCNA)/cyclin and of nuclear DNA content, was performed in quiescent and mitogen-stimulated human peripheral blood lymphocytes, in EUE (human embryonic epithelium) cells, before and after a long-term exposure to a hypertonic (HT) medium, in 4 human leukemic cell lines and in fresh bone marrow (BM) cells from 10 patients with untreated acute non-lymphoblastic leukemia (ANLL). The PCNA/cyclin was detected using both an autoantibody extracted from sera of systemic lupus erythematosus patients and the recently produced mouse monoclonal antibody (MoAb) IgG, named 19F4. The distribution of cells in the different phases of the cycle and the percentage of S-phase cells were obtained in duplicate samples, by DNA flow cytometry (FCM) and by dual parameter FCM of DNA content and bromodeoxyuridine (BUDR) incorporation. In all cell types, the non-specific cytoplasmic background fluorescence was significantly lower with the MoAb compared to that obtained with the polyclonal Ab. The percentage of PCNA-positive cells (both with the autoantibody and the 19F4 MoAb) was always higher than that of S-phase cells by DNA FCM and of BUDR-labeled cells. The pattern of PCNA-expression in both normal proliferating cells and acute leukemia cells, showed that most G0/G1 cells did not express significant amounts of PCNA; an increase in PCNA immunofluorescence was found in late G1 cells, and further increases were observed in S- and G2-M phase cells. PCNA/cyclin, as revealed both with autoantibodies and with the 19F4 MoAb, is associated with all actively or potentially dividing (i.e. G1, S and G2-M) cells thus identifying the proliferative cellular compartment. Combined with the use of multiparameter FCM techniques, the PCNA immunolocalization offers a useful tool to study cell kinetics in normal and leukemic human cell populations.

Antibodies, Monoclonal↗

Cell kinetics with in vivo bromodeoxyuridine and flow cytometry: clinical significance in acute non-lymphoblastic leukaemia.

From 1986 to 1988, 54 consecutive previously untreated patients with acute non-lymphoblastic leukaemia (ANLL), median age 54 years, were treated for remission (CR) induction with vincristine and intravenous medium-dose cytarabine sequentially followed by daunomycin and infusion cytarabine. CR patients received intensive consolidation. Bone marrow blast kinetics was studied before therapy with in vivo bromodeoxyuridine and bivariate flow cytometry. CR rate was 70.2%, median CR was 13.2 months, responsive patient survival was 16.9 months and overall survival was 9.2 months. Besides lower median age, the 33 responsive patients also had shorter potential doubling time (Tpot) and greater cell production rate (PR) than the 14 unresponsive patients (mean values = 10.9 vs. 25.4 days, P less than 0.05, and 14.7 vs. 8.9 cells/100 cells/day, P less than 0.02, respectively), due to a higher mean labelling index (7.0 vs. 5.1%, P less than 0.05) and/or to a shorter mean DNA synthesis time (13.6 vs. 18.6 hours, P less than 0.05). Besides lower white blood cell count and bone marrow blast percentage, patients who experienced CR longer than 13.2 months had shorter Tpot (P less than 0.05) and a greater PR (P less than 0.02) than those who relapsed before this time. These data indicate that kinetic parameters have prognostic relevance in ANLL patients treated with sequential vincristine, cytarabine and daunomycin for inducing CR and with intensive consolidation after CR, a high proliferative activity being a favourable factor for both CR achievement and its duration.

Adult↗

Postremission chemotherapy in adult acute non-lymphoblastic leukaemia including intensive or non-intensive consolidation therapy.

From October 1983 to December 1988, 84 consecutive adult patients with acute non-lymphoblastic leukaemia (ANLL; median age = 51 yr) were uniformly treated to induce remission (CR) with intravenous vincristine and cytarabine sequentially followed by daunomycin and infusion cytarabine. From October 1983 to December 1985 consolidation was non-intensive (2 courses with the same drugs used for induction) (protocol ANLL83: 27 patients, median age = 45). From January 1986 to December 1988 consolidation was intensive (4 courses of vincristine and cytarabine sequentially followed by etoposide plus thioguanine or amsacrine) (protocol ANLL86: 57 patients, median age = 57). Excluding early deaths, the CR rate was 71.6%. Median CR, responsive patient survival and overall survival were 11.1, 15.3 and 8.5 mo, respectively. For protocol ANLL83 and ANLL86, median CR was 8.7 and 13.2 mo (P less than 0.05) and median survival was 13.1 and 16.9 mo (P less than 0.05) for responders and 8.0 and 9.2 mo (P not significant) for all patients. Intensive consolidation including drugs not previously used for induction seems to prolong CR duration and responder survival in adult ANLL.

Adolescent↗