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Biomedical subjects

G Romano

Publications and source records attributed to G Romano.

At least 163 records · Page 9Linked to original sources

The iduronate sulfatase gene: isolation of a 1.2-Mb YAC contig spanning the entire gene and identification of heterogeneous deletions in patients with Hunter syndrome.

A recently isolated cDNA clone from the iduronate sulfatase (IDS) gene has been used both to seed a contig of overlapping yeast artificial chromosomes (YACs) and to investigate the molecular defect in patients with Hunter syndrome (MPS II). Six YAC clones were found to span the IDS gene, and those and 14 other YACs were assembled into a 1.2-Mb contig around the gene in Xq27-q28. The physical map of the region identifies several putative CpG islands, suggesting the presence of other genes in the vicinity. DNA from a patient with a translocation breakpoint in the gene also permitted the orientation of the contig in the chromosome. Southern analysis of DNA from 25 unrelated Italian Hunter syndrome patients revealed 4 with deletions or rearrangements in the IDS gene.

Blotting, Southern↗

Histone variants during sea urchin development.

The sea urchin genome contains several histone gene families whose expression is regulated in a developmental and tissue-specific fashion. The Cleavage Stage (CS) histone subtype is synthesized in unfertilized eggs and in embryos until the third cell cycle. The Early (E) subtype is synthesized during embryogenesis from the 2-4 cell stage to blastula. The only variant produced from the mesenchyme blastula stage to adult is the Late (L) subtype. In addition, two "sperm-specific" histone genes (SpH1 and SpH2B) are expressed exclusively in testis and their corresponding products are incorporated in sperm chromatin. In this review I will describe in some detail what is known about the characteristics of the various histone subtypes, with special focus on the Sp variants, and discuss the possible meaning of the presence of these histone variants during sea urchin development.

Animals↗

Role of inhibition of atrial natriuretic factor release in the down-regulation of salt excretion.

UNLABELLED: We investigated the role of atrial natriuretic factor (ANF) in the down-regulation of sodium excretion (UNaV). Seven subjects were sequentially studied while ingesting a normal-salt diet (220 mmol NaCl/day, NSD), a very low-salt diet (20 mmol NaCl/day, VLSD) for six days, and again at NSD for nine days. After one day of VLSD, a negative salt balance of 85 mmol was achieved and plasma ANF decreased from 19.1 (SE 2.5) to 7.2 (SE 2.1) pg/ml, whereas plasma renin activity (PRA) and plasma aldosterone (ALD) increased after the third and second day, respectively. During restoration of volemia (NSD), ANF increased after the third day; in contrast, PRA and ALD decreased earlier. Seven other subjects kept at low-salt diet (50 mmol NaCl/day) were studied during ANF infusion (at 2, 4, 8 ng/min/kg body wt). Increases of ANF from 10.3 (SE 0.9) pg/ml (basal condition) to levels of 24.0 (SE 1.9) pg/ml (infusion study), occurring physiologically in the same subjects after NSD, evoked increases in UNa V that accounted for 62% of UNa V rise necessary to balance the NSD, whereas PRA or ALD did not change. Plasma ANF, unlike PRA or ALD, was directly correlated with UNa V. IN CONCLUSION: (a) ANF changes earlier than PRA and plasma aldosterone during VLSD; (b) PRA and ALD respond more promptly than ANF in the recovery from hypovolemia; (c) during ingestion of a low-salt diet, changes in plasma ANF by infusion account for more than half the increase in UNa V following the shift from low- to normal-salt diet independently of alterations in PRA and ALD.

Adult↗

Inhibition of urea tubular reabsorption by PGE1 infusion in man.

We have shown that the inhibition of prostaglandin (PG) synthesis in man decreases the fractional clearance of urea (FCurea). To understand the mechanism(s) by which PG affect the renal handling of urea, 6 normal volunteers were randomly studied in maximal antidiuresis (by water deprivation and by administering 1-desamino-8-D-arginine vasopressin) before and during PGE1 infusion, in two separate occasions: (A) after 7 days of normal protein (1 g/kg b.w./day) and water intake (10 ml/kg b.w./day), and (B) after 7 days of low protein intake (0.5 g/kg b.w./day) and high water intake (80 ml/kg b.w./day) to lower the corticomedullary osmotic gradient. During infusion of PGE1 at rates of 0.01, 0.05 and 0.1 micrograms/min/kg, randomly administered, the urinary fluid losses were replaced by infusing equal volumes of hypotonic NaCl (80 mmol/l). To evaluate the time effects of this protocol, control studies were performed in an other 8 subjects receiving vehicle infusion without PGE1. In study A, FCurea rose by 23% (p less than 0.01) at the lowest PGE1 infusion rate (0.01 micrograms/min/kg), in the absence of any simultaneous change in water and salt output, Uosm, PAH and inulin clearance. Higher PGE1 infusion rates (0.05 and 0.1 micrograms/min/kg) were associated with a progressive increase of FCurea (50%, p less than 0.001 and 91%, p less than 0.001, respectively), fractional clearance of water and salt output, inulin and PAH clearance and reduced Uosm from 1,005 (22 SEM; basal value) to 772 (38 SEM; minimum value) mosm/kg (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Yeast artificial chromosome-based genome mapping: some lessons from Xq24-q28.

Yeast artificial chromosomes (YACs) have recently provided a potential route to long-range coverage of complex genomes in contiguous cloned DNA. In a pilot project for 50 Mb (1.5% of the human genome), a variety of techniques have been applied to assemble Xq24-q28 YAC contigs up to 8 Mb in length and assess their quality. The results indicate the relative strength of several approaches and support the adequacy of YAC-based methods for mapping the human genome.

Chromosome Mapping↗

Medium-term cyclosporin renal dysfunction and its reversibility in rats.

Renal dynamics and morphology were investigated by metabolic, renal micropuncture (RM), and electron microscopy (EM) studies in 50 female rats treated with cyclosporin A (CsA, 40 mg.kg body wt-1.48 h-1) for either 10, 20, or 30 days (groups CsA 10, CsA 20, and CsA 30, respectively); control rats received olive oil (group N). Body weight gain, sodium metabolism, and plasma volume were not altered by CsA administration in any group. GFR was decreased in group CsA 10 vs. group N (-10%, P less than 0.05) and was further impaired in groups CsA 20 and CsA 30 (-45%, P less than 0.01 vs. group N). RM studies showed a significant decrease of single-nephron glomerular filtration rate (SNGFR) in group CsA 30 vs. group N (-26%, P less than 0.01) after the fall of glomerular capillary pressure (Pgc;-8%, P less than 0.05), the increase of afferent arteriole resistance (Ra; +40%, P less than 0.05), and the consequent decrease of glomerular plasma flow (GPF; -28%, P less than 0.05). Thirty days after CsA withdrawal, SNGFR returned to normal values (P less than 0.01 vs. group CsA) as a result of the normalization of Pgc, Ra, and GPF.EM showed only a progressive vacuolation of proximal and distal tubular cells. These data suggest that medium-term administration of CsA is associated with reversible changes in glomerular dynamics and only mild histological lesions.

Animals↗

Acute effects of ciclosporin on renal hemodynamics and urinary protein excretion in patients with the nephrotic syndrome.

The possibility that the renal hemodynamic abnormalities associated with ciclosporin (CS) administration are enhanced in nephrotic patients (NP), leading to severe impairment of renal function and/or to modifications in proteinuria, has not hitherto been tested. Ten NP and 8 healthy subjects (NC) were examined before and after oral CS administration (10 mg/kg body weight in NP and 12 mg/kg body weight in NC: a lower dosage was adopted in NP because of edema overestimating the actual body weight) under water diuresis by standard renal clearance methods. Basal blood volume was lower in NP. Blood CS levels were not significantly different in the two groups. Basal glomerular filtration rate (GFR) was similar in NP and NC, while renal plasma flow (RPF) was lower in NP. After CS, both GFR and RPF significantly decreased in the two groups, but the percent decrease in inulin clearance was greater in NP. Filtration fraction increased only in NC. Basal renal vascular resistances were greater in NP, and significantly increased after CS in both groups. Basal fractional sodium excretion (FENa) was lower in NP: after CS FENa decreased only in NC. Neither plasma renin activity, nor plasma aldosterone changed after CS. When urinary protein excretion (UP) was corrected by GFR, no change was observed after CS; by contrast, selectivity of proteinuria (as assessed by the CIgG/CTransferrin ratio) markedly increased. Our data indicate that CS induces a greater fall in the GFR in hypovolemic NP than in healthy subjects, probably because in the former GFR becomes extremely plasma flow dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Determination of the "chromatographic pattern" for the identification of dipyrone urinary metabolites.

Sodium [N-(1,5-dimethyl-3-oxo-2-phenylpyrazolin-4-yl)-N-methylamino] methanesulfonate (dipyrone) cannot be detected as such in biological fluids since absorption is preceded by hydrolysis to 4-methylaminoantipyrine, which is actually absorbed and further metabolized. In the present work standardized TLC Rf values and gas chromatographic retention indices for the four main urinary metabolites of dipyrone were determined. Inclusion of these parameters in the principal component analysis "scores plot" allows dipyrone to be included as a possible candidate in the not oriented search for unknown drug assumption in cases of overdose intoxication or poisoning.

Adult↗

Differential expression of intercellular adhesion molecule 1 in primary and metastatic melanoma lesions.

Immunochemical studies have shown that the monoclonal antibody (MoAb) CL203.4, elicited with immune interferon treated cultured human melanoma cells Colo 38, recognizes intercellular adhesion molecule 1 (ICAM-1). The determinant defined by MoAb CL203.4 is distinct and spatially distant from that defined by anti-ICAM-1 MoAb RR1/1, which had been elicited with Epstein-Barr virus-transformed B-lymphocytes from a lymphocyte function associated antigen 1 deficient patient. Immunohistochemical testing with MoAb CL203.4 of surgically removed lesions of melanocyte origin has shown a markedly lower reactivity with benign than with malignant lesions. Among the latter, a higher percentage of metastatic than of primary lesions was stained by MoAb CL203.4. The higher expression of ICAM-1 in metastases than in primary lesions is unique to melanoma, since no difference was found in its distribution in primary and metastatic lesions of a variety of malignancies of different embryological origin. Reactivity with MoAb CL203.4 of primary lesions removed from patients with stage I melanoma showed a highly significant correlation with the lesion thickness and with the clinical course of the disease. The disease free interval in patients without detectable reactivity of their primary lesion with MoAb CL203.4 was significantly (P = 0.004) longer than that of patients whose primary lesion was stained with MoAb CL203.4. These results suggest that ICAM-1 may be a useful marker in the analysis of the molecular mechanism underlying the association between lesion thickness and clinical course of the disease.

Adolescent↗

Water sorption and mechanical properties of dental composites.

The physical properties of four commercial dental composites were investigated through differential scanning calorimetry, water sorption and desorption measurements and flexural mechanical properties tests. The differential scanning calorimetry curves of samples as prepared and after different times of ageing in water indicated that the small residual monomer reactivity, present in the as prepared samples, disappeared after immersion in water, which probably acts as a plasticizer and facilitates a further crosslinking reaction of the material and the residual monomer desorption. Consistently, water causes the embrittlement of the material, as detected from the flexural mechanical properties. Water sorption and desorption kinetics were measured at different temperatures, the water diffusion coefficients were calculated and the activation energies of the diffusion process were determined. The SEM analysis of the fracture surfaces and the decrease of the water uptake on the temperature indicated the existence of a good filler/matrix adhesion.

Adsorption↗

Decreased fibrinolytic activity in juvenile chronic arthritis.

The basal fibrinolytic activity in 17 children with active juvenile chronic arthritis (JCA) was investigated. It was found that patients with JCA, and particularly those with the systemic form, show decreased plasma fibrinolytic activity and a marked increase in plasminogen activator inhibitor. Additionally, it was found that patients with systemic JCA, but not those with the polyarticular or pauciarticular form, have increased circulating levels of tissue-type plasminogen activator, and endothelial cell protein, suggesting possible endothelial cell participation in systemic JCA.

Arthritis, Juvenile↗

Role of atrial natriuretic factor in renal adaptation to variation of salt intake in humans.

This study was performed to define the extent to which atrial natriuretic factor (ANF) contributes to upregulate salt excretion in subjects eating a high-salt diet. Eight normal volunteers were first studied at low-salt diet (80 mmol NaCl/day); urinary sodium excretion (UNaV) and plasma ANF (PANF) were measured in the basal condition and during stepwise infusion of human alpha-ANF at 2, 4, 8, and 16 ng.min-1.kg-1. Then the same subjects were shifted to a high-salt diet (400 mmol/day), and UNaV and PANF were measured in the new balance condition. At low-salt diet, UNaV averaged 0.069 meq/min, and PANF averaged 21 pg/ml; infusion of human alpha-ANF raised stepwise both UNaV and PANF (means in meq/min and pg/ml, respectively, were 0.177 and 46, 0.218 and 76, 0.360 and 86, and 0.601 and 182). Infusion of ANF caused a progressive fall of plasma aldosterone and plasma renin activity. Mean UNaV and PANF at high-salt diet were 0.301 meq/min and 35 pg/ml. Thus, by increasing experimentally PANF in a low-salt diet condition to the levels occurring physiologically in a high-salt diet condition, a significant rise in UNaV is evoked, which accounts for approximately 50% of the rise of UNaV that is necessary to balance the increased salt intake.

Adaptation, Physiological↗

[Peripuberal development of genetic obesity in beta rats. Daily changes in food intake, body weight, deep body temperature, triglyceridemia and glycemia].

The moderate quality of beta obesity and its relatively slow evolution make it potentially useful for defining the sequence of events that lead to the overt syndrome. Estimates of food intake, live body weight, deep body temperature, triglyceridemia and glycemia were obtained at several times during the day in beta genetically obese and alpha (alpha) control male rats at peripuberal age, in order to characterize the dynamic phase of this obesity and to attempt the definition of some previous proceedings that eventually produce the full obesity syndrome. Beta higher food intake in the light cycle preceded its whole day hyperphagia. Both genotypes showed the normal pattern of predominantly nocturnal feeding. A lower light phase's weight loss in beta preceded the overweight. Thus, beta rats were not significantly heavier than alpha until the end of the last period studied, when they were 75 days old. A defect in adaptive thermogenesis in beta genotype is suggested, as values on deep body temperature in relation to alpha were significantly lower at all times of day tested. Correlation coefficient value between daily net weight gain versus deep body temperature was: r = -0.601 (p less than 0.01), suggesting a diminished lipolytic stimulation in beta brown adipose tissue. A sustained hypertriglyceridemia in beta at every time of the day studied suggested its endogenous source. Differences in glycemia values were not statistically significant between genotypes, though apparently wider variations in beta could reflect a certain glycemic regulation lability in the obese genotype.

Animals↗

The inhibitory effect of aspirin on fibrinolysis is reversed by iloprost, a prostacyclin analogue.

The reduced fibrinolytic response after aspirin intake may be due to prevention of prostacyclin production. The effect of iloprost (a stable prostacyclin analogue) was tested on the fibrinolytic activity (euglobulin lysis area on fibrin plate [E.L.A.], t-PA antigen, PAI activity and PAI-1 antigen) of plasma drawn after venous stasis test from six healthy male volunteers, who each received all the following treatments according to a single-blind randomized cross-over design: placebo, iloprost, aspirin + placebo, aspirin + iloprost. The mean E.L.A. value after venous occlusion was significantly higher than the basal level after every treatment but aspirin. Within each treatment group the t-PA antigen levels in response to venous stasis were significantly higher than the basal ones. PAI-1 antigen levels did not change significantly before and after venous stasis either within or among the treatment groups. These data are consistent with the hypothesis that the mechanism related to aspirin's effect on fibrinolysis is mediated by suppression of vessel wall prostacyclin production. Aspirin's inhibitory effect on fibrinolysis was in fact prevented by replacing endogenous prostacyclin with iloprost. Iloprost enhances fibrinolytic activity reduced by aspirin, but not by promoting t-PA release or by inhibiting release of the specific inhibitor, PAI-1.

Adult↗

Hepatitis B virus infection in children in Sardinia, Italy.

Possible hepatitis B immunization of all newborns, regardless of the mother's HBsAg status, is a strategy under consideration for selected hyperendemic areas in Italy. Sardinia is one such area. However, in 1987 in Sardinia, the prevalence of hepatitis B markers in children under 11 years was estimated at 1.7% and the prevalence of hepatitis B surface antigen (HBsAg) at 0.2%. A much higher prevalence of HBsAg was recently observed among adults in this area: 8.7% among men and 5.2% among pregnant women. This contrasting pattern is unlikely to be due to bias: the sampling procedures adopted were appropriate and the percentage of refusals was very low (2.2%). The observed low hepatitis B marker prevalence in young age groups might be the result of a cohort effect due to the improved socio-economic conditions and changes in behaviour that have occurred in Sardinia over the last few years. The finding of only 3 HBsAg+ individuals out of 1,826 children tested, in spite of the 5.2% HBsAg prevalence among pregnant women in that region, is probably attributable to the low proportion of HBeAg positive individuals among the HBsAg+ carrier mothers in this area. At present, immunization of all newborns in Sardinia cannot be recommended.

Age Factors↗

Severe hemorrhage associated with pancreatic pseudocysts: report of two cases.

Severe hemorrhage from pancreatic pseudocysts is a rare condition that poses a diagnostic and therapeutic challenge. Two cases of preoperative intracystic bleeding and massive postoperative gastrointestinal hemorrhage observed during the last year form the basis of the present report. In the first patient, transcystic suture ligation of the bleeding vessel was necessary to control this life-threatening and dramatic condition--External drainage of the cyst was followed by an uneventful postoperative course. In the second patient, massive gastrointestinal bleeding occurred after cysto-gastrostomy, and neither endoscopy nor arteriography was able to identify the source. Despite aggressive medical and surgical therapy, the patient died. Massive intracystic or gastrointestinal hemorrhage caused by rupture of pseudoaneurysms into pancreatic pseudocysts still remains a rare but severe condition, difficult to treat and affected by high mortality rates. Angiography should be performed routinely in the preoperative assessment of pancreatic pseudocysts, even when the other diagnostic techniques do not raise the suspicion of pseudoaneurysm formation. After internal drainage procedures early surgery is recommended whenever GI bleeding occurs in the postoperative course.

Acute Disease↗

Molecular forms of immunoreactive gonadotropin-releasing hormone in hypothalamus and testis of the frog, Rana esculenta.

The hypothalamus and the testis of the frog, Rana esculenta, contain gonadotropin-releasing hormone (Gn-RH)-like peptides which are recognized by an antiserum raised against mammalian Gn-RH. Two molecular forms which coelute with synthetic chicken II and salmon Gn-RH from reverse-phase HPLC were distinguished in the hypothalamus. A single peak coeluting with synthetic chicken II Gn-RH was present in the testis.

Animals↗

Glomerular dynamics and salt balance in pregnant rats with renal hypertension.

These studies were aimed at investigating whether chronic hypertension in pregnancy causes changes both in salt excretion (NaE) and in glomerular hemodynamics. Metabolic and renal micropuncture studies were performed in pregnant (P) and Virgin (V) Munich-Wistar rats with normal blood pressure (N) and two-kidney Goldblatt hypertension (H). Mean NaE was higher in PN than VN (2.7 vs. 1.7 meq/day, P less than 0.01). Hypertension raised NaE both in P and V rats: in P and V rats with "benign" hypertension (blood pressure less than 180 mmHg) NaE averaged 3.2 and 2.6 meq/day, respectively (P less than 0.05); mean NaE was 5.9 and 3.8 meq/day, respectively (P less than 0.01), in P and V rats with "malignant" hypertension (blood pressure greater than or equal to 180 mmHg). Afferent arteriole resistance (Ra) averaged 1.73 and 3.50 10 dyn.s-1.cm5 in PN and VN, respectively (P less than 0.01). Hypertension raised Ra in V, but not in P rats (4.47 vs. 2.14 10 dyn.s-1.cm5, P less than 0.01). Thus glomerular plasma flow, glomerular capillary hydrostatic pressure, and single-nephron glomerular filtration rate were markedly higher in PH than VH rats: in PH rats single-nephron filtration fraction was significantly lower than in VH. These results show that in PH rats a marked rise in NaE is associated with glomerular vasodilation.

Animals↗