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G Mazzola

Publications and source records attributed to G Mazzola.

At least 37 records · Page 2Linked to original sources
PubMed1998

Polymorphisms in angiotensin-converting enzyme gene and severity of renal disease in Henoch-Schoenlein patients. Italian Group of Renal Immunopathology.

BACKGROUND: The influence of angiotensin converting enzyme (ACE) gene polymorphism on the progression of primary IgA nephropathy (pIgAN) is still debated. Even though the allele frequency was reported to be similar to controls, in some studies D/D patients had a faster decline of renal function and need of dialysis. Since Henoch-Schoenlein purpura (HSP) nephritis is considered a systemic vasculitis with renal lesions indistinguishable from pIgAN, we investigated the effect of the ACE polymorphism on presentation and progression of HSP IgAN. METHODS: We examined the insertion (I) and deletion (D) polymorphism in intron 16 of ACE gene by PCR amplification of genomic DNA of 82 patients (37 children), with biopsy-proven IgAN associated with HSP enrolled in a collaborative study. RESULTS: No significant association with clinical presentation at onset or with final outcome was found (functional impairment at outcome in 31.8%, D/D, 27.4%, I/D and 44% I/I, heavy proteinuria in 36.3% D/D, 21.6% I/D, and 11.1% I/I). Patients homozygous for the D allele had a greater number of extrarenal relapses (P=0.0028). No association was found between the ACE genotype and the presence of hypertension at onset and at the end of the follow-up. No difference was found between adults and children. CONCLUSIONS: In this cohort of HSP IgAN, no ACE I/D polymorphisms were found to be associated with progressive deterioration of renal function. Different genes possibly involved in vasculitis might more strictly modulate expression and evolution of HSP IgAN.

Adolescent↗
PubMed1998

Distribution of hepatitis C virus genotypes among intravenous drug users. A ten-year study in Palermo, Sicily.

A cross-sectional study was carried out on the sera of 88 active intravenous drug users (IVDU) collected between 1985 and 1986 to evaluate the circulation of HCV genotypes in Western Sicily. The patients were grouped by age and classified by their HIV status. Genotype 3a (48.8% of all cases) was most frequently detected, followed by genotype 1a (20.4%) and type 1b (17.0%). No significant differences in HCV genotype distribution were observed between HIV positive and negative individuals. Next, the HCV genotype distribution found in sera samples of IDVUs drawn between 1985 and 1986 was studied and divided into three age groups. The genotype distribution in the younger group was then compared with samples collected ten years later, between 1995 and 1996, from young HIV negative IVDU individuals. A different distribution between HCV genotypes 3a and 1a was found with a relative, though not significant, increase in the detection of genotype 1a (38%). Finally, sera from six IVDUs obtained at three different times over a ten-year period were genotyped for HCV. None of the subjects showed any change in the genotype found at the first sampling throughout the ten years. The results suggest that a) genotype 1a and 3a are the most common among IVDUs in Western Sicily, b) concurrent HIV infection does not seem to influence HCV genotype and c) infected IVDUs harbor almost exclusively one genotype.

Adolescent↗
PubMed1997

Immunogenetics of Henoch-Schoenlein disease.

In order to investigate the genetic basis of susceptibility to Henoch-Schoenlein purpura (HS), blood samples of 152 patients, 105 of whom had renal disease, were collected in a two-step study. The evaluation of DRB, DQB and DQA polymorphism was done by analysis of the restriction polymorphisms produced by TaqI enzyme. DRB1*07 was less frequent in patients than in the control group (gene frequency 0.09 and 0.18, respectively; P = 0.0023), whereas 64% of the patients were positive for DRB1*01 and/or DRB1*11 compared with 48% of the control group (P = 0.0069). Polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) typing of DRB1*01- and DRB1*11-positive individuals did not show any deviation of frequencies of DRB1*01 subtypes between patients and controls, whereas among DRB1*11 subtypes DRB1*1104 was significantly increased in the patients (Pc = 0.033). The comparison between patients with renal disease and those without renal disease showed no significant differences in the frequency of the single DRB, DQB and DQA alleles. The study of restriction polymorphisms in the switch region of the constant genes alpha 1, alpha 2 and mu of the heavy chains of immunoglobulins, using the enzyme Sacl and a specific probe, did not show any difference between 44 patients and 54 controls. This study demonstrates that susceptibility to HS also has a genetic origin: on one hand, the presence of DRB1*01 or DRB1*11 makes disease onset easier; on the other hand, DRB1*07 could induce some resistance to the disease. It is suggested that, as well as for other diseases caused by an impaired immune response, single amino acids in a key position in the HLA-DRB molecule make it more or less easy to recognize some antigenic peptide, towards which an immune response leading to disease is triggered.

Adolescent↗
PubMed1997

Human herpesvirus type 8 DNA sequences in biological samples of HIV-positive and negative individuals in Sicily.

OBJECTIVE: To evaluate the circulation of a new human herpesvirus (HHV), HHV-8 or Kaposi's sarcoma (KS)-associated herpesvirus in a geographical area where a high incidence rate of classical KS was already present before the appearance of the AIDS epidemic. DESIGN AND METHODS: The study was carried out by analysing: (i) bioptic samples from classic, AIDS-associated KS, and controls; (ii) peripheral blood mononuclear cells (PBMC) from classic KS, HIV-positive subjects with and without KS and healthy HIV-negative individuals; (iii) semen samples from heterosexual HIV-positive and HIV-negative individuals affected or not by KS; and (iv) cervical swabs from HIV-negative healthy heterosexual females. All specimens were tested for the presence of HHV-8 DNA sequences by a two-step polymerase chain reaction. RESULTS: Positive results were obtained in 90% of bioptic samples of classic KS and in 100% of AIDS-associated KS. Viral sequences were also present in 50% of PBMC of subjects with classic KS and AIDS-associated KS, in 10% of AIDS patients without the angiosarcoma and in 11% of healthy HIV-negative individuals. Finally, HHV-8 DNA was detected in 13% of semen of HIV-negative heterosexual individuals and in 10% of AIDS patients without KS. Both PBMC and ejaculates from the same individual gave positive results. No HHV-8 sequences were found in cervical swabs. CONCLUSIONS: HHV-8 is widespread in the general population in Sicily since it was detected in PBMC and semen of heterosexual HIV-negative individuals and is not found only in high-risk groups. The viral load appears to be more elevated in a high-risk population and it may be ascribed to a viral reactivation. The higher incidence rates of KS in Sicily compared with northern Italy and other European countries might be related to the presence of HHV-8 in the general population.

AIDS-Related Opportunistic Infections↗
PubMed1996

[The dependence of alcohol abuse and psychiatric comorbidity].

Aim of this paper, based on data collected at the General Hospital Psychiatric Unit of Pavia (Italy), is to study comorbidity between alcohol abuse/dependence and other mental illness. Thirty-five out of 188 patients admitted during the study period received a (DSM-III-R) diagnosis of alcohol abuse/ dependence and an other psychiatric diagnosis. Data were collected through a questionnaire, from patients and relatives, about history of dependence, psychiatric history both in patients and relatives, about life style and drinking opinions. Psycho-diagnostic (Wechsler, Rorschach) informations were obtained for 29 patients. Results show the importance of a complex treatment for both psychiatric and alcoholic problems.

Adult↗
PubMed1995

Prevalence of moderate hyperhomocysteinemia in patients with early-onset venous and arterial occlusive disease.

OBJECTIVE: To evaluate the prevalence of moderate hyperhomocysteinemia and inherited thrombophilia disorders (congenital defects of the natural anticoagulant or fibrinolytic mechanisms) in patients with early-onset venous or arterial thromboembolic disease. DESIGN: Cross-sectional 2-year evaluation of consecutive unrelated patients with a history of venous or arterial occlusive disease occurring before the age of 45 years or at unusual sites, in the absence of local predisposing factors. SETTING: Thrombosis research unit of a community hospital. PATIENTS: 107 patients with venous thromboembolism (mean age at event, 32.9 +/- 11.9 years) and 50 patients with arterial occlusive disease (mean age at event, 31.1 +/- 10 years) who did not have acquired coagulation defects, overt cancer, or acquired conditions affecting methionine metabolism. MEASUREMENTS: Total plasma homocysteine (fasting levels), antithrombin III, protein C, protein S, activated protein C resistance, plasminogen, and heparin cofactor II were measured at least 3 months after the event. In 87 patients, total plasma homocysteine levels were also measured 8 hours after an oral methionine load was administered (L-methionine, 0.1 g/kg body weight). Ninety-fifth percentiles of the distribution of these variables were established in 60 apparently healthy persons; sex-specific ranges were used for protein S and total plasma homocysteine. Relatives of patients with laboratory abnormalities were studied to confirm inheritance of the defects. RESULTS: Moderate hyperhomocysteinemia was detected in 13.1% (95% CI, 7.6% to 21.3%) and in 19.2% (CI, 9.0% to 31.9%) of patients with venous or arterial occlusive disease. The prevalence of hyperhomocysteinemia was almost twice as high when based on homocysteine measurements done after oral methionine load as when based on fasting levels. The remaining defects were detected only in patients with venous occlusive disease (activated protein C resistance in 11.2% of patients, protein S or C deficiency in 6.6%, and plasminogen deficiency in 0.9%), with an overall prevalence of 18.7% (CI, 12.1% to 27.6%). Inheritance of hyperhomocysteinemia and of the other defects was confirmed in 26 of the 30 families studied. Event-free survival analysis showed that the relative risk for occlusive disease in patients with moderate hyperhomocysteinemia and other defects was 1.70 times (CI, 1.19 to 2.42; P < 0.01) greater than in patients without defects. After adjustment for the presence of predisposing factors (for example, use of contraceptive drugs, pregnancy, surgery, prolonged bedrest, smoking, mild hypertension or dyslipidemia) and a family history of thrombosis, the age at first event of patients with moderate hyperhomocysteinemia was similar to that of patients with the other defects (26.4 +/- 11.2 years compared with 25.2 +/- 10.6 years), and the 43 patients with defects were significantly younger at first event than the 114 patients without defects (25.5 +/- 11.1 years compared with 31.0 +/- 12.3; P < 0.005). Patients with mild hyperhomocysteinemia had a higher rate of recurrence than those without defects (52% compared with 25%; P = 0.01); among the 56 patients who had their first event more than 1 year before observation, the recurrence rate was higher (80% [CI, 51% to 95%]) in patients with defects than in patients without defects (41% [CI, 26% to 57%] P = 0.01). CONCLUSIONS: Moderate hyperhomocysteinemia may have pathogenic significance in premature venous and arterial occlusive disease and should be included among the (inherited) disorders of venous and arterial thrombophilia.

Adult↗
PubMed1995

Heredity and obesity-associated hypertension: impact of hormonal characteristics and left ventricular mass.

OBJECTIVES: To investigate the influence of heredity on obesity-associated hypertension, we evaluated casual and 24-h blood pressure, left ventricular mass and some metabolic and hormonal measurements in normotensive obese subjects. DESIGN: Healthy, normotensive obese subjects (n = 81) with positive or negative family history of hypertension were studied. Both groups were also subdivided according to a positive or a negative family history of obesity. Accordingly, 45 obese subjects had a positive family history of hypertension, 25 of these having a positive (subgroup A) and 20 having a negative family history of obesity (subgroup B). The other 36 obese subjects had a negative family history of hypertension, 19 of these having a positive (subgroup C) and 17 having a negative family history of obesity (subgroup D). METHODS: Casual and 24-h systolic (SBP), diastolic (DBP) and mean blood pressure (MBP) were evaluated. Serum fasting blood sugar, total cholesterol and triglycerides levels, urinary excretion of sodium, immunoreactive fasting insulin, plasma ANF levels, plasma renin activity (PRA), plasma aldosterone level, plasma adrenaline and noradrenaline levels and echocardiographic total left ventricular mass (LVM) and LVM:height ratio were also calculated. RESULTS: Twenty-four-hour DBP, 24-h MBP, LVM, LVM:height ratio, total cholesterol and PRA values were significantly higher in normotensive obese offspring of hypertensive parents than in obese offspring of normotensive parents. Twenty-four-hour DBP and MBP, LVM, LVM:height ratio, insulin level, insulin:glucose ratio and PRA were significantly higher in subgroup A than in subgroup B. Fasting blood sugar level, 24-h DBP and MBP, insulin level, insulin:glucose ratio, PRA, noradrenaline, adrenaline and plasma aldosterone levels were significantly higher in subgroup C than in subgroup D. Multivariate analysis also indicated that 24-h MBP and PRA levels were significantly influenced by the association between a positive family history of hypertension and obesity. CONCLUSIONS: The present results suggest that a family history of obesity might increase the risk of developing hypertension in obese subjects. An elevated PRA may precede the development of hypertension in obese subjects who are at risk for developing hypertension.

Adult↗
PubMed1995

Severe autoimmune protein S deficiency in a boy with idiopathic purpura fulminans.

Idiopathic purpura fulminans usually occurs in young children and is frequently preceded by a preparatory viral or bacterial infection. Following a severe streptococcal pharyngitis, an 8-year-old boy developed purpura fulminans with disseminated intravascular coagulation and severe protein S deficiency (total antigen < 0.05 u/ml). Despite generous plasma infusions, skin necrosis progressed rapidly into compartment syndrome which required fasciotomy and skin grafting and resulted in the loss of three digits of the right foot. Total protein S remained low for over a month despite plasma supplementation and complete normalization of protein C levels. A polyclonal anti-protein S IgG was demonstrated in the patient's plasma, which decreased to 25% of baseline titre after 1 month and was undetectable 6 months after purpura fulminans, when plasma protein S had returned to normal. Transient, isolated and severe deficiencies of protein S have been reported in patients with idiopathic purpura fulminans and a previous preparatory infection. Autoimmune protein S deficiency may play a key role in the aetiopathogenesis of idiopathic purpura fulminans.

Autoantibodies↗
PubMed1995

Pulmonary toxicity of alpha tumor necrosis factor in patients treated by isolation perfusion.

We studied pulmonary function in 22 patients affected by in-transit metastases from cutaneous melanoma and metastases from soft tissue sarcoma of the limbs who were treated with isolation perfusion in extracorporeal circulation with rTNF alpha at doses ranging from 0.5 to 4 mg/m2 in mild hyperthermia. Seventeen patients suffered from respiratory insufficiency which required assisted ventilation (7 mechanical ventilation for 1 day, 8 for 2 days and 2 patients on synchronized intermittent mandatory ventilation). Spirometric parameters recorded 7 to 15 days after treatment did not change from baseline values; in contrast, lung transfer factor for carbon monoxide significantly declined in a dose dependent fashion. These data confirm that rTNF alpha administered by isolation perfusion technique induces pulmonary side effects. Further studies are required to better define time course and reversibility of impairment in pulmonary function.

Adult↗
PubMed1995

Usefulness of frequency analysis of cytotoxic T-lymphocytes precursors (CTL-p) for selection of HLA matched unrelated marrow donors.

A child with Sanfilippo syndrome and 5 potential unrelated marrow donors were typed serologically, tested in mixed lymphocyte reaction and typed by restriction fragment length polymorphism analysis in attempt to find a suitable donor. All donors were found to be identical with the recipient, however, these studies were not conclusive in identifying the best match donor. Therefore, recipient-donor pairs were examined by HLA-DR oligotyping. In addition we have studied the potential of cytotoxic T-lymphocytes precursors (CTL-p) analysis as a means of selection for matched unrelated donors. Low frequencies (1/10(5)) of pretransplant CTL-p correlated with oligotyping identity in all donor-recipient pairs evaluated. In one case oligotyping disclosed a previously unrecognized HLA-DRB1 disparity. This resulted in high frequencies of CTL-p (1/35,000). Based on this experience we can argue that CTL-p analysis may be used as an additional tool for selection of compatible unrelated marrow donors.

Bone Marrow Transplantation↗
PubMed1994

Protein S and protein C anticoagulant activity in acute and chronic cardiac ischemic syndromes. Relationship to inflammation, complement activation and in vivo thrombin activity.

Protein S (PS) and protein C (PC) anticoagulant activities and thrombin-antithrombin complex (TAT) were measured in 20 patients with AIS, 25 patients with chronic stable angina (CSA) and a control group (C). Although plasma levels of TAT were significantly elevated in patients with CSA (p < 0.01 vs C), they were much higher in patients with AIS (p < 0.001 vs CSA). PC anticoagulant activity was similar in patients and controls. At variance, PS anticoagulant activity was lower in patients with AIS than in those with CSA and controls (p < 0.05), reflecting differences in total PS and C4B-binding protein (C4B-BP) antigen possibly resulting from involvement in the mechanisms of inflammation, complement activation and acute-phase response. The ratios of anticoagulant PS and PC to procoagulant vitamin K-dependent factors IX and II were reduced in AIS patients (0.05 > p > 0.005 vs C). In addition, the ratios of anticoagulant PC and PS to factor IX were lower in patients with AIS than in those with CSA (p < 0.05). These results indicate that in patients with acute ischemic cardiac syndromes the markedly increased in vivo thrombin generation is associated with an unbalance between coagulant and anticoagulant vitamin K-dependent factors.

Acute Disease↗
PubMed1994

HLA supratypes in an Italian population.

A supratype analysis of a North Italian population was performed, using 16 polymorphisms in the HLA region spanning the HLA-A-DP segment. Fourteen supratypes were identified, mostly corresponding to those found in other Caucasoid populations. The degree of their conservation both within the B-DR/DQ region and in the regions telomeric and centromeric from HLA-A and DP was evaluated and linkage disequilibria among several DR and DP alleles were identified. Notably, the degree of association with DP increased when the DR marker was part of a conserved B-DR/DQ supratype. These data are relevant to the definition of the genetic structure of the population and to the prediction of probabilities of histocompatibility matching between unrelated individuals.

HLA Antigens↗
PubMed1994

A practical approach to HLA-DR genomic typing by heteroduplex analysis and a selective cleavage at position 86.

A common problem facing HLA-typing laboratories is to substitute genomic typing for serology without having to handle a large number of oligoprobes, primers, or restriction enzymes. A protocol is described for HLA-DRB1 genomic typing using a combination of PCR amplification, DNA heteroduplex analysis, and restriction enzymes. Because the core of the procedure is the analysis of the DNA heteroduplexs, it shall be termed HET typing. There are two stages: the first stage comprises two rounds of PCR amplification of the polymorphic second exon of the HLA-DRB genes directly on lysed blood cells. The first amplification is with DRB generic primers, and the second amplification with seven HLA-DRB1 group-specific primers at the 5' end and a common 3' primer. The latter is designed with two nucleotide mismatches, thus creating an artificial restriction site to differentiate between both HLA-DRB1 variants at position 86, which is of critical importance in antigen presentation. The second stage involves subjecting the final amplified product to both DNA heteroduplex formation and digestion by two single-cutter restriction endonucleases. The digested or heteroduplexed samples are run on the same polyacrylamide gel. A total of 25 HLA-DRB1 alleles can thus be differentiated with a total of 10 primers and two restriction enzymes and without the use of probes. This protocol is ideally suited to preliminary HLA class II typing of bone marrow donors.

Alleles↗
PubMed1994

Human leukocyte antigen class II polymorphisms and genetic susceptibility of IDDM in Egyptian children.

OBJECTIVE: To analyze the association between human leukocyte antigen (HLA) and insulin-dependent diabetes mellitus (IDDM) in the Egyptian population for the first time and, thus, to determine the frequency of risk-associated alleles identified by a genomic HLA class II typing. Egyptians are genetically classified as North Africans and considered to be between Caucasoids and Africans (closer to Caucasoids). RESEARCH DESIGN AND METHODS: HLA class II typing was performed for 50 IDDM patients and 50 healthy control subjects by a restriction fragment-length polymorphism (RFLP) technique. The analysis of position 57 of the DQB1 molecules was conducted by polymerase chain reaction and specific sequence oligonucleotide hybridization. RESULTS: The frequency of DRB1*0301-DRB3*0201-DQA1*0501-DQB1*0201 haplotype was 43.9% in the IDDM patients and 7.1% in the control subjects (P < 0.00001), reflecting the increased prevalence of DQA1*0501 susceptibility allele coding for arginine (Arg) in position 52 and DQB1*0201 susceptibility allele non-coding aspartic acid (Asp) at position 57. Alleles DQB1*0601 and 0603, both carrying Asp at position 57 of the beta-chain, and DQA1*0103, encoding a non-Arg 52 alpha-chain, were significantly decreased among the IDDM patients. The presence of four susceptibility residues (two DQA1 Arg 52+ and two DQB1 Asp 57-) conferred the highest relative risk at 20.2. On the other hand, homozygous genotypes for DQA1 non-Arg 52 and DQB1 Asp 57 were found only in the control group. CONCLUSIONS: IDDM susceptibility and resistance in the Egyptian population is strongly associated with the expressed DQ alpha- and beta-heterodimers in a dose-effective manner, as already defined in many different ethnic groups.

Alleles↗
PubMed1994

Frequencies of HLA class II alleles in Piedmont (northern Italy).

HLA class II gene frequencies were analysed in a panel of 101 unrelated individuals with Piedmontese ancestors living in Piedmont (north western Italy). A class II genomic typing was performed using the XI Histocompatibility Workshop protocol based on locus specific amplification by Polymerase chain Reaction (PCR) of class II gene second exon and hybridization with sequence specific oligonucleotides (SSO). Compared to other HLA typing techniques, this protocol defines more class II subtypes and analyses HLA-DP gene polymorphisms. The frequencies of alleles at DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, DPA1, DPB1 loci are reported. Linkage disequilibrium analysis between DPA1-DPB1 and DRB1-DPB1 alleles is also reported.

Alleles↗