Sperm-mediated gene transfer: production of pigs transgenic for a human regulator of complement activation.
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Animals↗
Biomedical subjects
L Pucci
Publications and source records attributed to L Pucci.
Inter- and intrachromosomal rearrangements are both involved in the origin of 15q11-q13 deletions in Prader-Willi syndrome.
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Chromosomes, Human, Pair 15↗
Transcapillary escape rate of albumin in type II diabetic patients. The relationship with microalbuminuria and hypertension.
OBJECTIVE: To study why in type II diabetes, microalbuminuria, a marker of generalized vascular dysfunction, and hypertension have been linked with both renal and cardiovascular organ damage. RESEARCH DESIGN AND METHODS: To investigate the effect of moderately elevated blood pressure on vascular damage, the transcapillary escape rate of albumin (TERalb) was measured by intravenous injection of purified 125I-human serum albumin in 9 healthy control subjects (group 1), 9 nondiabetic hypertensive subjects (group 2), and 73 nonobese type II diabetic patients stratified as follows: group 3: 17 normoalbuminuric-normotensive subjects; group 4: 22 normoalbuminuric-hypertensive subjects (systolic blood pressure [sBP] > or = 140 mmHg or diastolic blood pressure [dBP] > or = mmHg or both); group 5: 16 normotensive subjects with microalbuminuria (albumin excretion rate [AER]: 20-200 micrograms/min); and group 6: 18 microalbuminuric-hypertensive subjects. RESULTS: Groups 3-6 had similar age, sex, duration of diabetes (group 3: 7.8 +/- 5.5; group 4: 9.7 +/- 8.7; group 5: 12.1 +/- 8.1; and group 6: 10.7 +/- 8.3 years), BMI, HbA1c (7.8 +/- 1.1, 7.5 +/- 1.5, 8.7 +/- 1.5, and 7.7 +/- 1.1%, respectively), blood glucose, and lipid profile. Systolic and diastolic blood pressure did not differ in the three hypertensive group (group 2: 154 +/- 3/99 +/- 6; group 4: 149 +/- 13/95 +/- 6; group 6: 154 +/- 15/91 +/- 9 mmHg) and were significantly lower (P < 0.001) in group 3 (126 +/- 12/76 +/- 7), group 5 (128 +/- 11/77 +/- 5), and healthy control subjects (group 1: 133 +/- 7/81 +/- 4). TERalb was similar in control subjects (5.77 +/- 1.06%/h) and in normoalbuminuric-normotensive subjects (5.81 +/- 1.51%/h) but significantly higher (P < 0.0001) in microalbuminuric subjects with or without hypertension (9.11 +/- 1.65 and 8.60 +/- 1.50%/h, respectively) as well as in normoalbuminuric diabetic patients with hypertension (8.10 +/- 2.27%/h) and in essential hypertensive subjects (8.12 +/- 1.68%/h). CONCLUSIONS: By stepwise regression, TERalb was related (step 1) to log-AER (r = 0.30) or to the presence of microalbuminuria (r = 0.36) and (step 2) to dBP (multiple r = 0.40) or to the presence of hypertension (multiple r = 0.51) in the whole diabetic cohort (groups 3-6). TERalb was related to dBP (r = 0.47) or to the presence of hypertension (r = 0.56) only in normoalbuminuric diabetic patients (groups 3 and 4) and to log-AER (r = 0.56) or the presence of microalbuminuria (r = 0.68) only in normotensive patients (groups 3 and 5). In type II diabetic patients, TERalb was elevated in subjects with increased albuminuria, irrespective of blood pressure levels, but also was independently related to the presence of mild-to-moderate systemic hypertension.
Adult↗
[Hypertension and diabetes].
The prevalence of hypertension in diabetes is significantly higher than in non-diabetics, perhaps twice as common. The excess is related to diabetic nephropathy, mainly in type 1 diabetes, to obesity, mainly in type 2 diabetes, but also to increased sympathetic activity. Furthermore, the increased prevalence of hypertension may relate to insulin resistance and its sequelae. Insulin resistance leads to hyperinsulinemia, relates to increased LDL and reduced HDL levels, causes the development of impaired glucose tolerance and type 2 diabetes and might also be causally related to the onset of hypertension. Syndrome X has relevant therapeutic implications in the management of hypertension. Hypertension is a major risk factor for large vessel disease in diabetics and also a risk factor for microangiopathy, particularly nephropathy. The incidence of atherosclerotic disease is dramatically increased in both type 1 and type 2 diabetics and is the major cause of morbidity and premature death mainly in patients with raised urinary albumin excretion. Thus, diabetics show a two-fold increased risk of coronary heart disease, 2-6 fold increased risk of stroke and a several-fold increased risk of peripheral vessel disease. Some evidence suggests that hypertension may be a risk factor for retinopathy, particularly its progression, but surely hypertension is a significant risk factor for nephropathy, accelerating its progression and perhaps even causing the onset of the glomerulopathy. The mechanisms by which hypertension might contribute to the evolution of both large vessel as well as small vessel disease is still unknown, although increased capillary leakage and vascular endothelium alterations might be important factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Antihypertensive Agents↗
[Correlation of the clinical phenotype with a pericentric inversion of chromosome 9].
Pericentric inversion of chromosome 9 is one of the most common structural balanced chromosomal aberrations. It is considered as a paraphysiological variant of a normal karyotype and it is possible to find it as occasional report in healthy subjects. In the last ten years different signals have appeared in literature, concerning carriers of pericentric inversion of chromosome 9, who showed different anomalies of the clinical condition. Today it is difficult, because of the rarity of the data to establish if a true correlation exists between phenotypical anomalies in the subjects studied and the pericentric inversion, or if they are only casual associations. We are trying to find possible correlations between the chromosomal rearrangements and eventual congenital defects. We describe 11 subjects with pericentric inversion of chromosome 9 examined for the presence of dysmorphic signs, mental retardation and repeated miscarriage.
Abnormalities, Multiple↗
[Familial segregation of simple and complex chromosomal rearrangements].
We report our observations about familial segregations of chromosomal aberrations: the simple forms and complex rearrangements. Congenital malformations and mental retardation, can be present both in unbalanced and in balanced translocations. Various hypotheses have been proposed to explain this phenomenon: in particular a possible "position effect" or genic mutation or genomic imprinting. In our study we have used both standard techniques and techniques with high resolution banding to investigate if the rearrangements were balanced or not. Molecular study and gene dosage have been used when possible, to define the correlation with the clinic phenotype.
Abnormalities, Multiple↗
[Correlations between karyotype and phenotype in structural and numerical abnormalities of chromosome 18].
Five cases with different abnormalities of chromosome 18 are described: one case with trisomy 18, two cases with ring 18, one case with partial trisomy 18q and one case with a mosaic 18p-/iso 18q. The karyotypes of the parents were normal. Cytogenetic analysis was performed on PHA stimulated blood lymphocytes. GTG, QFQ, MTX banding techniques were used. Karyotype-phenotype correlations are made. All patients present mental retardation, hypotonia and facial dismorphisms. The different degree of mental retardation and the clinical signs are in relation to the different size of deletions or trisomies of the short or long arm of chromosome 18. In the case with mosaicism 18p-/iso18q the phenotype is determined from the chromosomal abnormality more frequent in the cells (18p-).
Abnormalities, Multiple↗
[Primary adenocarcinoma of the appendix].
One case of primary adenocarcinoma of the vermiform appendix is presented. The patient, a 55-year-old man, showed non specific symptoms and the diagnosis was made after surgery. Surgical treatment was right hemicolectomy. The patient is still alive and disease-free 12 months after the operation. The Authors review the literature and discuss some clinical aspects of this rare tumor.
Adenocarcinoma↗
Growth hormone secretion in Prader-Willi syndrome.
Prader-Willi Syndrome (PWS) is a multisystem defect characterized by obesity, hypogenitalism and short stature for genetic background. Low GH serum levels have been found in patients with PWS and were related to a hypothalamic-pituitary dysfunction. We studied spontaneous nocturnal GH secretion and GH-response to provocative tests in five patients affected by PWS. We observed in three of them (Group A) abnormally low GH and IGF-1 serum levels. In the other two patients (Group B) GH secretion and IGF-1 serum levels were normal. In all patients no thyroid dysfunction was observed. These data might suggest the presence of two different subgroups of patients affected by PWS, from an endocrinological point of view. An abnormally low GH secretion would be evident only in a subgroup of patients, which appears to be normal in the remaining patients. This casistic is small in number, but if our data will be confirmed by more extensive studies it may be possible to identify a specific population of PWS patients who could benefit from recombinant GH-therapy.
Adolescent↗
Replication of circular and linear SV40-based plasmids in monkey cells.
Three plasmids were derived from a common SV40-based parent. A circular plasmid (pYACneoC) contained the SV40 ori and two sets of 50 bp of human telomeric sequences. By differential enzyme digestion, two linear plasmids were generated from the circular form, one (pYACneoL) terminating with, and the other (pYACneoN) free of telomeric sequences. The replicative features of the circular and of both linear plasmids were assayed by transfecting COS-7 cells. At various times after transfection, the low-molecular-weight DNA was extracted, and the fraction of molecules that had replicated was determined by Dpnl digestion. We demonstrate that about half of the circular plasmid molecules replicate, but only during a short time interval immediately following transfection. No replication was observed in the case of the two linear plasmids. However, the function of the SV40 origin is potentially present in the molecules, since circular forms that do replicate can be recovered from both linear plasmids. The extent of replication of circularized pYACneoL is similar to that of pYACneoC, whereas a lower fraction of circularized pYACneoN molecules replicate. These results are discussed in terms of the possible influence of the DNA structure on the viral ori, and of the influence of the host cell functions on viral replication.
Animals↗
Human decay accelerating factor transgenic pigs for xenotransplantation obtained by sperm-mediated gene transfer.
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Animals↗
The mechanism of oxidation of allylic alcohols to alpha,beta-unsaturated ketones by cytochrome P450.
The oxidation of cyclohex-2-en-1-ol, a simple model substrate for allylic alcohols, is catalyzed by several P450 isoenzymes and leads exclusively to cyclohex-2-en-1-one. No double bond epoxidation or C(4) hydroxylation have been observed. The large primary kinetic isotope effect measured using [2H]-1-cyclohex-2-en-1-ol is consistent with an at least partially rate limiting breaking of the C(1)-H bond. The mass spectrometric analysis of cyclohex-2-en-1-one obtained from [18O]cyclohex-2-en-1-ol has established that a gem-diol intermediate is involved, even if a dual hydrogen abstraction pathway may contribute to the reaction.
Allyl Compounds↗
[Integrin Beta 3 PlA1/PlA2 polimorphism does not contribute to complications in both type 1 and type 2 diabetes].
BACKGROUND: The glycoprotein IIIa (beta3 integrin) is an integral part of two glicoprotein receptors of platelets and, respectively, endothelium and vascular smooth muscle cells. The gene encoding the GPIIIa, a receptor for fibrinogen, vWF and fibronectin, shows polymorphism (PlA1/PlA2); the PlA2 allele has been associated with myocardial infarction, stroke and cardiovascular disease. METHODS: Seven hundred and thirty-two subjects with type 1 diabetes and 605 subjects with type 2 were recruited. The prevalence of complications in type 1 diabetes was: microalbuminuria (uA) 17%, overt nephropathy (MA) 10%; background retinopathy (bR) 27%, proliferative retinopathy (pR) 22%; hypertension (HYP) 13%; coronary heart disease (CHD) 9%. The respective figures for type 2 diabetes were: uA 34%, MA 21%; bR 38%, pR 18%; HYP 80%; CHD 26%. A 247 bp fragment (exon 2) was amplified by PCR. For the detection of the point mutation CDGE (Constant Denaturing Gel Electrophoresis) after optimum denaturing conditions setting by DGGE (Denaturing Gradient GE) and/or RFLP by NciI digestion were employed. RESULTS: In type 1 diabetes, PlA1PlA1/PlA1PlA2 distribution was 77/23%. No differences were found among normoalbuminuric (nA: 76/24%), microalbuminuric (uA: 79/21%) and macroalbuminuric subjects (MA: 75/25%, p=0.79) as well as among subjects with no retinopathy (Ret-) (74/26%), bR (76/24%) and pR (78/22%, p=0.81), and between HYP- (78/22%) and HYP+ (72/28%, p=0.27) as well as CHD- (76/24%) and CHD+ (75/25%, p=0.72). Systolic blood pressure, HbA1c and retinopathy were independent predictors of nephropathy. No contribution of diastolic BP, sex, BMI, duration of diabetes and PlA2 allele was found for the risk of nephropathy. In type 2 diabetes, PlA1PlA1/PlA1PlA2/PlA2PlA2 distribution was 74.4/23.3/2.3%, with no differences foud among nA (73/25/2%), uA (75/23/2%) and MA (81/17/2%, p=0.66). No significant difference was detected among subjects with Ret- (74/22/4%), bR (77/22/1%) and pR (77/22/1%, p=0.62). Also, no differences were found between HYP- (81/17/2%) and HYP+ (74/24/2%, p=0.28) as well CHD- (76/22/2%) and CHD+ (74/24/2%, p=0.93). Systolic BP, HbA1c, presence of retinopathy, gender and BMI were independent predictors of nephropathy. Diastolic BP, duration of diabetes and PlA2 allele did not contribute to the risk of nephropathy. CONCLUSIONS: The PlA1/PlA2 polymorphism of the GPIIIa gene does not contribute to the development of nephropathy or retinopathy in type 1 and type 2 diabetes. Furthermore, no association was found between the PlA1/PlA2 polymorphism, hypertension, and coronary heart disease.
Adult↗
[Treatment of iatrogenic lesions of the common bile duct].
The authors report 32 patients admitted to the hospital with iatrogenic bile duct stricture. Cholecystectomy with or without bile duct exploration was the most frequent (84.3%) surgical procedure responsible for the lesion, followed by BII gastric resection. Six patients had undergone one previous attempt at repair in another institution. Most patients had undergone a hepatojejunostomy, which has the procedure of choice in the last cases. Mortality and morbidity rates were 0 and 15%, respectively. The complications reported were a biliary fistula and 2 post-repair bile strictures that required one or more re-operations. During the follow-up 2 other patients developed episodes of cholangitis, treated medically. Clinical, diagnostic and therapeutic aspects of iatrogenic bile duct strictures are reviewed.
Adult↗