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Biomedical subjects

G Mazzola

Publications and source records attributed to G Mazzola.

At least 55 records · Page 3Linked to original sources
PubMed1993

Identification of unrelated HLA-identical bone marrow donors: RFLP, oligotyping and PCR fingerprinting for HLA class II compared to MLC responses.

22 patients awaiting bone marrow transplantation (BMT) and 65 unrelated healthy HLA-A, B and DR serologically identical donors were studied. 21 patients were non reactive on mixed lymphocyte culture (MLC) towards at least one BMT donor, resulting in 32 pairs MLC-negative. 33 other HLA-matched donors gave proliferative responses on MLC. The phenotype DR3/DR7 was significantly higher in patients (P) and donors (D) studied (p < 0.00001). P and D pairs were DNA typed by RFLP analysis for DRB, DQA and DQB genes, and DNA matched by PCR Fingerprinting (PCRF) for DRB, DQA, DQB and DPB. Six patients and 18 donors were also oligotyped for the subtypes of DR1, DR3, DR4 and DR5. Patients and donors were divided according to identity on RFLP, PCRF and responsiveness on MLC, represented by RRI. In the group of MLC non responder pairs, 11% had differences on DRB PCRF compared to 57% in the group of MLC responders (p = 0.0002). The mean RRI value of PCRF DRB incompatible pairs was significantly higher compared to RRI of compatible pairs (p = 0.012). With respect to PCRF for DPB, 75% of MLC-ve pairs were different. Also the mean RRI value was significantly lower in DPB identical pairs compared to non identical ones (p = 0.048). The compatibility between P/D pairs assessed by oligotyping was in accordance with DRB PCRF. PCRF for DQB, but not for DQA, corresponded to MLC responses. Our findings confirm that PCRF offers a precise and fast alternative in DNA matching for DRB. We also suggest that PCRF for DQB and DPB, together with DRB, could eventually substitute MLC.

Bone Marrow Transplantation↗
PubMed1993

Double-blind controlled study of rilmenidine versus hydrochlorothiazide in mild hypertension: clinical and renal haemodynamic evaluation.

Clinical and renal haemodynamic parameters were evaluated in 20 mild hypertensive patients after rilmenidine (RIL) administration during a one month double-blind randomised study compared with hydrochlorothiazide (HCT). At the beginning and at the end of the study, BP, heart rate and renal haemodynamic parameters were evaluated. Renal haemodynamic parameters included effective renal plasma flow (ERPF) evaluated by radionuclide study utilising 131I-Hippuran according to Schlegel's method, effective renal blood flow (ERBF = ERPF/(1-Ht)), glomerular filtration rate (GFR) by creatinine clearance, filtration fraction (FF = GFR/ERPF) and renal vascular resistances (RVR = DBP x 80/ERBF). RIL and HCT significantly (P < 0.01) reduced systolic, diastolic and mean blood pressure without relevant change in ERPF, ERBF, GFR and FF. RVR was significantly reduced both in the RIL group (P < 0.002 vs. baseline) and in the HCT group (P < 0.001 vs. baseline). No relevant side-effects were observed in either group. In conclusion, rilmenidine was effective in reducing BP in mild hypertensive patients and produced favourable effects on renal function.

Adult↗
PubMed1992

The genetics of IgG4 deficiency: role of the immunoglobulin heavy chain constant region and HLA loci.

IgG4 deficiency is very common (1/400 in the Italian population) and provides a good model for analyzing the genetic factors involved in Ig subclass deficiencies. We have previously reported an association between some immunoglobulin heavy chain constant region (IGHC) polymorphisms and the IgG4 deficiency. The associated polymorphisms spanned the region between the GP and the G4 genes. A larger sample composed of 50 healthy blood donors with IgG4 deficiency (less than 0.001 g/l IgG4), not carrying homozygous gene deletions, together with 82 first-degree relatives is now examined. The results confirmed the association of the deficiency with IGHC polymorphisms, and detected a new association with the HLA-D locus with a strong additive effect between the two systems. However, despite these associations and a highly significant risk for IgG4 deficiency within families, close linkage with either IGHC or HLA loci was not apparent by the affected sib pair method. These findings suggest that several concomitant, possibly cooperating, genetic factors may be involved in IgG4 deficiency.

Chromosome Mapping↗
PubMed1992

Familial occurrence of primary glomerulonephritis: evidence for a role of genetic factors.

Chronic glomerulonephritis was diagnosed in 23 patients born in a small valley in Northern Italy and in five additional patients with one parent or a more remote ancestor born in the same area, all belonging to three potentially related families. Eighteen patients had biopsy-proven glomerulonephritis: 11 IgA nephropathy, 3 IgM nephropathy, 2 membranoproliferative type I, and 2 mesangial proliferative glomerulonephritis with isolated C3 deposits. Ten had clinical glomerulonephritis. A community screening programme discovered six additional related patients. Two underwent renal biopsy (1 IgA nephropathy; 1 focal glomerulosclerosis); four were diagnosed as having clinical glomerulonephritis. Genealogical investigation identified five deceased family members with diagnoses of chronic nephritis recorded on their death certificates. No environmental nephrotoxic factors were identified. Restriction fragment length polymorphism (RFLP) analysis of HLA-DR beta, HLA-DQ alpha and beta genes, and complement typing for C4A, C4B, and Bf polymorphisms were carried out for 29 patients, 168 healthy relatives, and 24 local controls. The frequency of HLA-Dw8.1 specificity, related to DR beta 8, DQ beta 3b, and DQ alpha 1a RFLPs, was significantly increased more in the affected and unaffected pedigree members than in Italian controls.

Adolescent↗
PubMed1992

Immunoglobulin and HLA-DP genes contribute to the susceptibility to juvenile dermatitis herpetiformis.

HLA-DQ genes and gluten diet are the main factors involved in the pathogenesis of Dermatitis Herpetiformis (DH), as well as Coeliac Disease (CD). However other genetic factors are probably relevant, since about 10% of the patients with DH and CD lack the DQA1*0501/B1*0201 heterodimer while the majority of individuals presenting this genotype and also being exposed to gluten diets did not suffer from these diseases. To evaluate the role of other genes, 36 Northern Italian children with DH were analysed for DNA polymorphisms at HLA-DP and immunoglobulin (Ig) heavy chain loci. DPA1*0201 and DPB1*1301 frequencies were higher in patients than in controls (Pc = 0.0357 and Pc = 0.0273). With respect to immunoglobulin heavy chain restriction fragment length polymorphisms (RFLP), the 4.6 kb SacI RFLP at the switch alpha 2 gene was more frequent in patients (0.13) than in controls (0.019; Pc = 0.036). Moreover, rare alleles or duplications in the switch regions occurred more frequently in the patients than in the controls. These results support the hypothesis of a multifactorial inheritance of DH, the HLA and Ig constant heavy chain genes being some of the loci contributing to the susceptibility. In accordance with previous CD studies, these data also confirm that DP subregion is probably involved in the pathogenesis of DH.

Adolescent↗
PubMed1992

Immunologic characteristics of fibrillary glomerulonephritis.

IgG and IgA immune complexes, mononuclear phagocytic system function, interleukin-2 (IL-2) production by peripheral blood lymphocytes (PBL), serum-soluble IL-2 receptors, tumor necrosis factor, beta 2-microglobulin and IL-1 beta, HLA-DNA polymorphisms, immuno-isoelectrofocusing, phenotype of PBL, lymphocyte cytotoxicity, activation of lymphokine-activated killer cells and natural killer cell activity were evaluated in 8 patients with tubular/fibrillary glomerulonephritis (GN). No common serologic, immunologic or immunogenetic features suggestive of plasma cell dyscrasias were found. No elements to state whether these GNs represent a new entity or just atypical forms of known GN were found.

Adolescent↗
PubMed1992

Hormonal profiles in Italian late-onset adrenal hyperplasia correlate with HLA class III polymorphisms.

To investigate the genetic polymorphisms of the HLA region in late-onset adrenal hyperplasia, 13 Italian patients affected by the disease were analyzed for: (1) HLA-A and -B typing; (2) restriction fragment length polymorphism (RFLP) of DR beta, DQ beta, DQ alpha, 21-hydroxylase A and B genes; (3) fourth complement fraction loci A and B (C4A and C4B), second complement fraction (C2) and properdin B factor (Bf) complement typing; (4) hormonal characteristics associated with some HLA haplotypes. HLA alleles B14 and DR beta 1 were found to be significantly more frequent in patients with respect to controls (relative risk: 8.7 and 7.2, p less than 0.001 and p less than 0.0001, respectively). Also C4B*2, 1 duplication was more frequent in patients than in normal subjects (23% vs. 1.5%, p less than 0.0001). Moreover, patients carrying a duplicated C4B (as well as those having the B14 antigen) showed higher 17-hydroxyprogesterone levels after ACTH stimulation. RFLP analysis of 21-hydroxylase genes with a specific probe revealed a duplication of 21-hydroxylase A gene in 40% of patients. All these individuals carried the C4A*2 B*2,1 phenotype and 75% of them displayed a clearly recognizable duplication at the C4B locus. These data support the hypothesis that in late-onset adrenal hyperplasia the 21-hydroxylase A pseudogene, even if inactive, may play a negative role in the regulation of 21-hydroxylase biosynthesis. Furthermore, we suggest analyzing class III phenotypes to screen the enzymatic defect.

17-alpha-Hydroxyprogesterone↗
PubMed1990

The HLA-DR beta 16 allogenotype constitutes a risk factor for hypertrophic scarring.

Nineteen patients that had developed hypertrophic scars subsequent to thermal injury were typed for HLA class II allogenotypes with the restriction fragment length polymorphism technique. A significant association was found with DR beta 16 (pc = 1.45 x 10(-4); relative risk = 12.25). This finding adds evidence to other data suggesting that immunologic phenomena are involved in pathologic scarring. Moreover, the results presented here have allowed an identification of a genetically determined risk factor for hypertrophic scar formation located in the HLA region.

Cicatrix↗
PubMed1990

HLA in juvenile dermatitis herpetiformis: clinical heterogeneity correlated with DNA and serological polymorphism.

A group of 30 Italian children affected by Dermatitis Herpetiformis (DH) was analysed for HLA region polymorphisms with both serological and DNA methods. Serological typing was performed on HLA-A, B, C, DR, DQ antigens and C4A, C4B, Bf polymorphisms. DNA RFLPs obtained with TaqI enzyme were investigated with cDNA probes specific for DR beta, DQ alpha and DQ beta genes. The results were correlated with intestinal involvement and age at onset of the disease. The following observations were made: (1) the intestinal biopsies revealed a direct correlation between degree of lesions and age at onset of DH; (2) a significantly increased relative risk (RR) was found for the following HLA antigens: A1 (RR = 2.2), B8 (RR = 6.2), Cw7 (RR = 3.9), C4AQ0 (RR = 7.4), DR3 (RR = 5.2), DR7 (RR = 4.4), DRw53 (RR = 4.7), DQw2 (RR = 6.0); (3) B8 and DR3 were significantly more frequent in patients with severe intestinal lesions; and (4) of the two DR3 subtypes revealed by RFLP typing, only 3.1 showed an increased frequency in DH patients (RR = 8.4). It is suggested that the susceptibility to Juvenile DH is determined by the same genes, within the HLA region, that are associated with Coeliac Disease.

Adolescent↗
PubMed1990

Familial IgM mesangial nephropathy: a morphologic and immunogenetic study of three pedigrees.

Eight patients belonging to 3 unrelated families had biopsy-proven IgM mesangial nephropathy. In the first family, the mother and the 2 daughters were affected; in the second, the mother and the son; in the third, 2 sisters and the brother. Two additional sisters of the third family showed a clinical picture consistent with chronic glomerulonephritis. The clinical picture was that of hematuria and/or proteinuria. No patients had nephrotic syndrome. Genealogic investigation enabled us to discover 2 additional affected members in the kindred of the first family (1 with IgA nephropathy, 1 with clinical glomerulonephritis) and 3 other affected members in the pedigree of the third family (1 with IgA nephropathy, 1 with sclerosing glomerulonephritis, 1 with clinical glomerulonephritis). Immunogenetic studies showed the recurrence of an extended haplotype bearing DR beta 11-DQ beta 3B-DQ alpha 2-C4A3-C4B1-BfS in 9 of 10 affected members. Our data suggest that genetic factors may be involved in the mechanism of the disease and support the hypothesis that IgM nephropathy is a distinct disease entity.

Adolescent↗
PubMed1990

Hypertension in obese subjects: distinct hypertensive subgroup.

Obesity and hypertension are two closely associated conditions and obesity probably predisposes to hypertension. In this investigation we evaluated central, systemic haemodynamic and intravascular volume characteristics of 51 established hypertensive obese subjects subgrouped for degree of obesity. Subgrouping according to body mass index (BMI) was as follows: lean hypertensives, 17 subjects (BMI 23.00 +/- 0.45 Kg/m2); moderately obese, 19 subjects (BMI 26.92 +/- 0.30 Kg/m2); severely obese, 15 subjects (BMI 32.78 +/- 0.45 Kg/m2). Obese hypertensives were characterised by significantly increased cardiac output and total plasma volume (P less than 0.05) and by decreased total peripheral resistance (not significantly) and left ventricular ejection fraction (P less than 0.01). These changes appear to be related to the degree of obesity. Significant correlation coefficients between body mass index and cardiac output, total blood volume, total peripheral resistance and ejection fraction were also observed. In conclusion, established hypertension in the severely obese patient appears to be a separate haemodynamic entity.

Adult↗
PubMed1989

Denaturation by urea and renaturation of 20 beta-hydroxysteroid dehydrogenase studied by high-performance size exclusion chromatography.

The denaturation by urea and renaturation of 20 beta-hydroxysteroid dehydrogenase, a tetrameric enzyme consisting of four identical subunits, were followed by high-performance size exclusion chromatography to detect intermediates in the processes. During the denaturation process no intermediate form (structured monomers or dimers) between the tetramer and the denatured monomer was observed. During the renaturation process, carried out either with or without NADH, high molecular weight aggregates, native tetramers, and low molecular weight intermediates were evidenced and quantified. The contemporaneous measurement of recovery of activity unambiguously demonstrated that the tetrameric structure is essential for enzymatic activity.

20-Hydroxysteroid Dehydrogenases↗
PubMed1989

[Evolution of the echographic picture in primary liver tumor associated with cirrhosis].

To study the sonographic (US) evolution of hepatocellular carcinoma, 53 tumors in 45 untreated patients were observed regularly with real-time US for a period of 6 to 56 months. At the beginning, 25 tumors were hypoechoic, 18 isoechoic, 4 hyperechoic, and 6 had mixed hypo/hyper echo patterns. At the follow-up, 7 initially hypoechoic tumors had changed to hyperechoic or to mixed echo patterns; 8 hypoechoic tumors had become isoechoic; 9 of the 25 initially hypoechoic neoplastic lesions had maintained the same echo density. Ten of the 15 initially isoechoic tumors had changed to mixed echo patterns, and 5 had remained unchanged. Three initially isoechoic lesions and a hypoechoic one had turned into diffuse patterns; 2 initially hyperechoic neoplastic lesions had remained unchanged; 1 had switched into hypoechoic, and 1 changed to mixed echo pattern; 4 out of 6 tumors with echo pattern had remained unchanged, 1 had become hyperechoic and 1 hypoechoic. The current study has proven various tumors less than or equal to 3 cm phi to be isoechoic, and most tumors greater than 3 cm phi to have mixed hypo/hyper echo patterns. The echogenicity of small hepatocellular carcinomas increases with the tumor growth, and remains unchanged when they do not increase in size.

Aged↗
PubMed1989

[Clinical and hemodynamic effects of medium-term ketanserin treatment in 2 compared groups of obese and non-obese hypertensive patients].

We evaluated systemic and central hemodynamics in 10 lean hypertensives and in 10 obese hypertensives (WHO stage I-II) after 8 weeks treatment regimen with a serotoninergic antagonist such as ketanserin. At the beginning and at the end of the study, body weight, BMI, blood pressure and heart rate were measured and a first pass radionuclide angiocardiography was performed to determine cardiac output, cardiac index and ejection fraction of left ventricle. Total peripheral resistances were also calculated. In both hypertensive groups ketanserin significantly reduced diastolic (p less than 0.05) and mean (p less than 0.005) blood pressure. No significant change in systolic blood pressure, cardiac output, cardiac index and ejection fraction of left ventricle has been observed in lean and obese hypertensives. Total peripheral resistance values significantly (p less than 0.05) decreased in lean hypertensives; in obese hypertensives total peripheral resistance moderately reduced. Our results indicated that monotherapy with ketanserin is effective in treating mild to moderate hypertension both in lean and in obese hypertensives and did not interfere with left ventricular performance. At last the effectiveness of ketanserin treatment appears moderately higher in lean than in obese hypertensives.

Adult↗
PubMed1987

The binding site for alpha-bungarotoxin resides in the sequence 188-201 of the alpha-subunit of acetylcholine receptor: structure, conformation and binding characteristics of peptide [Lys] 188-201.

In order to study where the binding site of cholinergic agents is in the sequence of the alpha-subunit of nicotinic acetylcholine receptor (AChR), we have synthetized 3 peptides with an amino acid sequence corresponding to the following sequences of the alpha-subunit of Torpedo californica AChR: 125-143, 158-167, [Lys] 188-201. For binding studies the peptides were immobilized on Sepharose 4B. Only the peptide [Lys] 188-201 binds 125I-alpha-bungarotoxin (alpha-Bgtx) with Kd of 1.03 microM. The binding of 125I-alpha-Bgtx to the peptide is reduced by 85% after reduction of the S-S bridge present between 192-193 cysteines indicating that an intact disulfide bond is important for toxin binding. The 125I-alpha-Bgtx binding is inhibited by curare, decamethonium, hexamethonium but not by carbamylcholine and Naja naja siamensis alpha-toxin and P15 toxin. All these data provide direct evidence that the sequence 188-201 of the alpha-subunit of AChR binds alpha-Bgtx and that this binding has a pharmacological profile similar to that of nicotinic acetylcholine receptor.

Amino Acid Sequence↗
PubMed1987

Multiparameter study of denaturation of 20 beta-hydroxysteroid dehydrogenase by urea in the presence of stabilizing agents.

We investigated the denaturation of tetrameric 20 beta-hydroxysteroid dehydrogenase (20R)-17 beta,20 beta,21-trihydroxysteroid:NAD+ oxidoreductase, EC 1.1.1.53) to find out whether intermediate states are formed during the process. The denaturation process was studied in the presence and absence of stabilizers, both specific, such as NADH, and non-specific, such as the salting-out anion phosphate. Changes in enzymatic activity, intrinsic protein fluorescence and far-ultraviolet circular dichroism were monitored. When NADH was present, denaturation of the enzyme by urea was a one-step transition between the native and the completely denatured state. In dilute phosphate, and even more so in concentrated phosphate, the existence of intermediate states with different stability is evidenced by the noncoincidence of the transition curves that probe for different functional and conformational aspects of the enzyme. Therefore, for 20 beta-hydroxysteroid dehydrogenase the formation of intermediates can be prevented by adding NADH, or enhanced by adding concentrated phosphate.

20-Hydroxysteroid Dehydrogenases↗