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Biomedical subjects

M Nardi

Publications and source records attributed to M Nardi.

At least 109 records · Page 6Linked to original sources

Trapidil inhibits endothelial cell proliferation and angiogenesis in the chick chorioallantoic membrane and in the rat cornea.

The effects of trapidil, a coronaro-active drug which has been shown to inhibit the mitogenic activity of platelet derived growth factor (PDGF), have been investigated on the proliferation of the human endothelial cells (HUV-EC-C), on the neovascularization in the chorioallantoic membrane of the chick embryo (CAM) as well as on the angiogenesis of rat cornea following chemical injury. The proliferation of HUV-EC-C in the presence of trapidil (25 and 250 micrograms/mL) was significantly inhibited by 19 and 25% respectively, compared to controls. On 2-days old CAMs, agarose disks containing 100-150 micrograms of trapidil produced an avascular zone indicating significant antiangiogenic activity, while control agarose disks were without effect. Corneal neovascularization was induced by applying a silver nitrate/potassium nitrate applicator to the rat eyes. A 6-day-treatment with eye drops of a solution of 10 mg/mL trapidil significantly decreased the rate of vessel growth compared with vehicle controls. The antiangiogenic activity of trapidil was markedly increased by the association with hydrocortisone (1.34 mg/mL). These results suggest that trapidil, alone or in combination with a steroid, could be a promising candidate for the therapy of corneal diseases in which alterations induced by neovascular growth play a substantial role.

Allantois↗

[A rare case of Meckel's diverticulum perforation].

Meckel's diverticulum is a pathology not rarely found everyday clinical medicine especially when it present with one of its complications. The specific diagnosis is a bit difficult to put because of the low sensibility and specificity of symptoms of diagnostic and instrumental techniques used. The reported case shows a rare type of complication constituted by the phlogosis of Meckel's diverticulum, itself due to an extraneous thing ingested by the patient. The authors discuss the entity of the manifestations of this pathology and highlight every aspects.

Acute Disease↗

[Branchial carcinoma].

The Authors report three cases of epidermoidal carcinoma arising from a congenital cyst of the anterolateral region of the neck. This type of tumor, rarely found in daily practice, arises from a degenerate branchial tissue and differential diagnosis often includes nodal involvement from systemic neoplasias. However, diagnostic criteria of such diseases are well defined; furthermore the rarity of branchial carcinoma is opposed to the high frequency of metastatic lymph nodes deriving from tumors with similar histological aspects located in other sites which could alter the real percentage of branchial tumor manifestation.

Aged↗

Biochemical and genetic characterization of PepF, an oligopeptidase from Lactococcus lactis.

Lactococcus lactis possesses a complex proteolytic system which is essential for its growth in milk. We characterized one of the peptidases of this system, oligopeptidase PepF, together with its structural gene. PepF hydrolyzed peptides containing between 7 and 17 amino acids with a rather wide specificity. It was purified to homogeneity. The N-terminal sequences of PepF and of peptides resulting from tryptic digestion of PepF were determined and used to design degenerate oligonucleotides which served to amplify a DNA fragment internal to pepF. This fragment was used as a probe to screen a lactococcal genomic library in Escherichia coli and to clone the entire gene pepF. The gene coded for a 70 kDa protein and was located on a 55-kilobase lactose-protease plasmid. A motif His-Glu-X-X-His, characteristic of metallopeptidases was evidenced. Two regions of PepF were found similar, first to a stretch of 43 amino acids around the zinc-binding site of several other peptidases, second to a stretch of 33 amino acids well conserved among creatine and arginine kinases. Preliminary results suggest the presence of a second copy of pepF.

Amino Acid Sequence↗

Gene cloning and characterization of PepC, a cysteine aminopeptidase from Streptococcus thermophilus, with sequence similarity to the eucaryotic bleomycin hydrolase.

Streptococcus thermophilus CNRZ 302 contains at least three general aminopeptidases able to hydrolyze Phe-beta-naphthylamide substrate. The gene encoding one of these aminopeptidases was cloned from a total DNA library of S. thermophilus CNRZ 302 constructed in Escherichia coli TG1 using pBluescript plasmid. The wild-type TG1 strain, although not deficient in aminopeptidase activity, is unable to hydrolyze the substrate Phe-beta-naphthylamide, and thus the library could be screened with an enzymic plate assay using this substrate. One clone was selected which was shown to express an aminopeptidase, identified as a PepC-like enzyme on the basis of cross-reactivity with polyclonal antibodies directed against the lactococcal PepC cysteine aminopeptidase. The gene was further subcloned and sequenced. A complete open reading frame coding for a 445-residue (50414 Da) polypeptide was identified. 70% identity was found between the deduced amino acid sequence and the sequence of PepC from Lactococcus lactis subspecies cremoris, confirming the identity of the cloned gene. High sequence similarity (38% identity) was also found with an eucaryotic enzyme, bleomycin hydrolase. In addition, the predicted amino acid sequence of the streptococcal PepC showed a region of strong similarity to the active site of cysteine proteinases with conservation of the residues involved in the catalytic site. The product of the cloned pepC gene was overproduced in E. coli and was purified from a cellular extract. Purification to homogeneity was achieved by two-step ion-exchange chromatography. Biochemical characterization of the pure recombinant enzyme confirms that the cloned peptidase is a thiol aminopeptidase possessing a broad specificity. The enzyme has a molecular mass of 300 kDa suggesting an hexameric structure. On the basis of sequence similarities as well as common biochemical and enzymic properties, the bacterial PepC-type enzymes and the eucaryotic bleomycin hydrolase constitute a new family of thiol aminopeptidases among the cysteine peptidases.

Amino Acid Sequence↗

Crystallization and preliminary X-ray analysis of PepC, a thiol aminopeptidase from Lactoccocus lactis homologous to bleomycin hydrolase.

Crystals of the recombinant thiol aminopeptidase PepC, from Lactoccocus lactis, have been obtained using the hanging-drop method of vapor diffusion from ammonium sulfate solutions. Crystals are rhombohedral, the space group is R32, a = 175.2 A, c = 94.5 A (hexagonal setting). The asymmetric unit probably contains one monomer of a hexameric molecule-arrangement of 300 kDa which exhibits the crystallographic point group of symmetry 32. The crystals diffract to at least 3 A resolution.

Aminopeptidases↗

Effects of short- and long-term carvedilol administration on rest and exercise hemodynamic variables, exercise capacity and clinical conditions in patients with idiopathic dilated cardiomyopathy.

OBJECTIVES: The study evaluated the effects of short- and long-term administration of carvedilol in patients with idiopathic dilated cardiomyopathy. BACKGROUND: Carvedilol is a beta-adrenergic blocking agent with vasodilator activity that might be well tolerated in patients with heart failure. METHODS: Forty patients with idiopathic dilated cardiomyopathy treated with digoxin, furosemide and angiotensin-converting enzyme inhibitors were randomized in a double-blind manner to receive either placebo or carvedilol. Right heart hemodynamic variables were evaluated up to 8 h after short-term drug administration and, on the next day, during cardiopulmonary exercise testing before and 3 h after drug ingestion. Placebo or carvedilol was added to standard therapy, starting with a dose of 6.25 mg twice a day with weekly increments up to the maximum of 25 mg twice a day. Patients were reevaluated after 4 months by cardiopulmonary exercise testing and measurement of right heart hemodynamic variables 12 h after last drug ingestion and 3 h after drug readministration. Left ventricular ejection fraction and volume, measured by equilibrium radionuclide ventriculography, quality of life and submaximal exercise duration were assessed before and after long-term therapy. RESULTS: Compared with placebo, carvedilol produced a short-term reduction in heart rate and pulmonary artery and pulmonary wedge pressures and, after long-term administration, increased both rest and peak exercise cardiac, stroke volume and stroke work indexes, with a further reduction in right atrial, pulmonary artery and pulmonary wedge pressures. Long-term carvedilol administration also improved rest left ventricular ejection fraction (from 20 +/- 7% to 30 +/- 12%, p < 0.001), submaximal exercise capacity, quality of life and New York Heart Association functional class. No baseline variable was predictive of the response to therapy. CONCLUSIONS: Short-term carvedilol administration reduces heart rate and mean pulmonary artery and pulmonary wedge pressures, whereas it improves both long-term rest and exercise left ventricular systolic function, reduces heart failure symptoms and improves submaximal exercise tolerance in patients with idiopathic cardiomyopathy.

Adrenergic beta-Antagonists↗

Effect of low molecular weight heparan sulphate on angiogenesis in the rat cornea after chemical cauterization.

Vascularization of the cornea occurs in many pathological conditions and can result in loss of visual acuity. It is also thought that vascularization predisposes the cornea to reject grafts by facilitating the detection of foreign antigens in donor material. A rat corneal assay for angiogenesis was adopted in the present study to evaluate the possible angiostatic activity of a low molecular weight heparan sulphate (LMW-HS). Corneal lesions were induced by chemical cauterization at 2 mm from the corneoscleral limbus. Rats were randomized to receive two drops/eye four times daily, for 6 days, of a solution of LMW-HS in vehicle (2.5% carboxymethylcellulose), heparin, heparin plus hydrocortisone, or vehicle alone. After a 6 day-treatment period, the eyes were perfused with india ink and the degree of neovascularization was evaluated. In rats treated with vehicle alone a dense vascular network extending from the corneoscleral limbus to the cauterized site was observed; on the contrary, a markedly reduced vascular network was evidenced in animals treated with LMW-HS. The distribution of basic fibroblast growth factor (bFGF) in the cauterized cornea was also evaluated by using an immunohistochemical method. A marked bFGF immunoreactivity was demonstrated in corneal epithelium and stroma of control rats 12-48 hours after the cautery. These results lead to the assumption that LMW-HS could be used in ophthalmology to inhibit corneal neovascularization.

Animals↗

[Results of conservative surgery in T1 breast carcinoma. Our experience in 66 treated cases].

Between 1989 and 1991, 66 women affected by breast cancer smaller than 2 cm in diameter, were treated with conservative procedure plus radiotherapy. Conservative procedure consisted in quadrantectomy and axillary dissection of the 3 axillary nodes levels. Neoplasms were grouped according to TNM classification. Eleven were classified as Tis, 9 as T1aN0M0, 12 as T1bN0M0, one case T1bN1M0, 24 as T1cN0M0 and finally 9 as T1cN1M0. Actuarial 5-year survival rate was related to TNM. It has been reported to be 100% in Tis and T1aN0M0 neoplasms; 91.7% in pT1bN0M0 tumors, 95.8% in pT1cN0M0 neoplasms, 55.6% in patients affected with pT1cN1M0 tumors. According to the relationship between receptor status of the neoplasm and survival, this was 88.9% in ER+ and 77.8% in ER- tumors, and 97.1% against 71.4% (p < 0.05) in PR+ and PR- neoplasms respectively. Two patients presented (3%) local recurrence which were treated by means of a tumorectomy and radiotherapy. Both patients are still living and disease free after 6 and 9 months from re-operation.

Adult↗

[The effects of sublingual nifedipine on isometric stress in patients with severe aortic insufficiency. An acute hemodynamic study].

We studied the acute hemodynamic effects of nifedipine (N) on handgrip test (Hg) in 10 patients with aortic regurgitation in II NYHA functional class. In basal condition (B) we found a significant increase of mean aortic pressure (AoPmean) in all patients after Hg (101 +/- 9.72 versus 110.3 +/- 6.42 mmHg; p < 0.05). Hg did not induce significant changes of AoPmean after N. Hg increased left ventricular end-diastolic pressure (LVEDP) from 13.3 +/- 6.4 to 20.5 +/- 9.9 mmHg (p < 0.01) before N and from 9.7 +/- 3.2 to 12.8 +/- 5.5 mmHg after N (NS). LVEDP measured during Hg after N showed lower values than those measured before N (12.8 +/- 5.5 versus 20.5 +/- 9.9 mmHg; p < 0.01). Cardiac index (CI) increased by Hg in B (3.7 +/- 0.7 versus 4.0 +/- 1.1 L/min/m2; NS) and after N (4.5 +/- 0.7 versus 4.9 +/- 0.9 L/min/m2; NS). CI increased significantly after N at rest (3.7 +/- 0.7 versus 4.5 +/- 0.7 L/min/m2; p < 0.01) and during Hg (4.0 +/- 1.1 versus 4.9 +/- 0.9 L/min/m2; p < 0.01). The left ventricular stroke work index (LVSWI) decreased during Hg from 74.4 +/- 20.6 to 71.2 +/- 20.0 g.m/m2; NS. N caused an increase at rest to 81.4 +/- 22.5 g.m/m2; NS. LVSWI increased significantly during Hg to 83.5 +/- 26.2 g.m/m2; p < 0.05. Systemic arterial resistances (SAR) significantly decreased after N at rest (1,086.8 +/- 280.8 versus 843.5 +/- 133.1 dyne.s.cm-5; p < 0.01), but increased in B during Hg to 1,220.9 +/- 350.7 dyne.s.cm-5; p < 0.05. A significant reduction of SAR values was observed alter N during Hg (1,220.9 +/- 350.7 versus 838.9 +/- 139.9 dyne.s.cm-5; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

[Blood levels of somatotropic hormone in patients with various degrees of heart failure].

BACKGROUND: The hypothesis that in normal pituitary patients (pts) with heart failure the heart is a target-organ of the hypophysis has not be held in due consideration. Aim of the study was: 1) to determine Growth Hormone (GH) plasma levels in pts with various degree of heart failure; 2) to evaluate the relationship between GH, left ventricular mass and some haemodynamic and endocrine parameters of ventricular dysfunction. MATERIALS AND METHODS: Blood samples for determination of GH and Atrial Natriuretic Factor (ANF) were collected 24 hours before haemodynamic study. Plasma concentrations of GH and ANF were determined by radio-immuno-assay in 20 normotensive pts (age ranging 31 to 54) without mellitus diabetes in IV (10 pts) and III (10 pts) NYHA FC: Echocardiographic determination of left atrial diameter, end-diastolic and end-systolic left ventricular diameters, index of left ventricular mass (ILVM), were performed. All pts underwent right and left cardiac catheterization and coronary angiography. RESULTS: The pts in IV NYHA FC, Group A, had lower cardiac index (IC) (1.8 +/- 0.4 vs 2.9 +/- 0.1, p < 0.0001) and higher GH and ANF plasma levels than those in III NYHA FC, Group B (4.9 +/- 4.5 vs 0.12 +/- 0.04, p < 0.01; 157.9 +/- 43.9 vs 65.6 +/- 14.6, p < 0.0001). No significant difference was found by comparing in both groups ILVM (212.6 +/- 64.7 vs 192.9 +/- 71.9, NS). GH and ANF plasma levels were 4.1 +/- 5.0 and 113.8 +/- 59.6 in pts with ILVM > or = 200 g/mq and 0.9 +/- 2.7 and 109.7 +/- 57.3 in pts with ILVM < 200 g/mq (no significant statistical difference). We found an high correlation by comparing GH and ANF in group with ILVM > or = 200 g/mq (r = 0.82, p < 0.005) and in group with ILVM < 200 g/mq (r = 0.68, p < 0.05). CONCLUSIONS: Our study demonstrated: 1) increased GH plasma levels in pts with severe heart failure; 2) an high correlation between GH and ANF plasma levels in pts with ILVM > or = 200 g/mq.

Adult↗

[Internal hernias. Description of 2 cases].

The authors describe two cases of recent observed internal-hernia, regarding in the first case the right para-duodenal dimple, and in the second a mesenteric breach. They report the clinic presentation and the diagnostic and therapeutic approach compared with the data deriving from the international literature. A complete clinical classification of the internal-hernia is illustrated showing the different clinical signs. The respective symptomatology that in the initial phases of this pathology is not too evident, shows that the internal hernia should always be held in due consideration at the moment of diagnosis because the consequent mortality due to complications such as intestinal-gangrene is rather high.

Aged↗

[Cancer of the gastric stump. Our experience].

The authors discuss their experience of six cases of cancer of the gastric stump observed by them in the period from 1988 to 1992 inclusive. All the patients were operated; five total gastrectomies and a gastric re-resection were effected. In association also the spleen was removed in four patients, in one of them a hepatic metastasectomy and a distal pancreasectomy were effected. In the discussion the problems concerning the diagnostic and therapeutic implications with some references to the more likely etiopathogenetic theories were dealt with.

Adenocarcinoma↗

[Extraperitonealization of the liver in the Chilaiditi syndrome].

The Chilaiditi syndrome or viscero hepato diaphragmatic interposition is a rare anomaly. The authors describe one case they observed. Even if it is often asymptomatic, it may manifest also by recurrent sub-occlusion or occlusion. Only a few patients need corrective surgical operation. The operation of choice is hepatic extra-peritonealization, which after replacement of the dislocated gastroenteric tract, brings the superior face of the liver again into direct contact with the related diaphragmatic dome.

Aged↗

[Lumbar hernia of Grynfeltt's quadrilateral space. Apropos a case].

The authors discuss a case of Grynfeltt's quadrilateral lumbar hernia in an 85-year-old patient. These rather rare hernias can be classified as Grynfeltt's hernias of the superior lumbar space, as Petit's inferior lumbar space and as diffused hernias concerning the whole hip. In our case this hernia was located in the superior lumbar space and it was delimited on the upper part by the 12th rib and by the serratus posterior-inferior muscle; in the lower part by the internal oblique muscle and by the lumbar quadratus muscle. Surgical treatment was effected by plastic surgery with synthetic material put in the extra-peritoneum space and fixed by serum-muscular stitches. Postoperative control effected after a month from the operation proves a good keeping of the plastic surgery reconstruction with total disappearance of the hernia.

Aged↗

Human megakaryocytes have a CD4 molecule capable of binding human immunodeficiency virus-1.

Most human megakaryocytes (MGKs) express the CD4 antigen on their surface. Approximately 25% have a CD4 receptor density comparable to that of CD4+ T cells (Basch et al, Proc Natl Acad Sci USA 87:8085, 1990). In these studies, we show: (1) the presence of mRNA for CD4 in human MGKs; (2) the binding of human immunodeficiency virus-1 (HIV-1) to human MGKs; (3) the inhibition of binding by anti-CD4 (Leu3a) antibody or rCD4; (4) the infection of a human MGK line, CHRF-288 with HIV-1; and (5) inhibition of infection with anti-CD4. Human MGKs have mRNA for CD4 as shown by in situ hybridization with an RNA probe synthesized from a 3-kb cDNA sequence of plasmid pSP65.T4.8 containing the full-length CD4 sequence. MGKs (23% +/- 17%) bound HIV-1, as determined by anti-gp120 and anti-CD41 staining. Binding to human MGKs could be inhibited 55% to 75% with anti-CD4 or rCD4, respectively. Infection of a CD4+ MGK line (CHRF-288) could be accomplished with HIV-1, as determined by proviral DNA polymerase chain reaction and p24 production. Preincubation with anti-CD4 inhibited apparent proviral DNA infection by 100% and p24 production by 65% to 70%. Thus, human MGKs have a CD4 receptor capable of binding HIV-1. Using this receptor, HIV-1 can infect cells representative of the MGK lineage.

Antigens, CD↗