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G Giudice

Publications and source records attributed to G Giudice.

At least 55 records · Page 3Linked to original sources

[Magnetic resonance in the evaluation of lesions of the posterior tibial tendons].

Posterior tibial tendon (PTT) tears are the most common cause of unilateral flatfoot in adults. It is a chronic pathologic condition with a degenerative inflammatory character which usually affects middle-aged or elderly women, with no history of trauma. PTT tears occur more rarely in young patients, after an acute traumatic event. Clinically, PTT tears present with pain along the tendon, increased by weight bearing, swelling and functional limitation. PTT tears are surgically classified in three types: with tendon hypertrophy, with tendon atrophy and with complete tendon tear. The three different anatomicosurgical patterns require different therapeutic approaches. This work was aimed at investigating MR capabilities in recognizing the direct and indirect signs of PTT tears, assessing MR sensitivity in different types of tears. Fourteen patients with clinically suspected PTT tears and 10 control patients underwent MRI of the ankle (0.5 T, GE Vectra) following a study protocol including SE T1-weighted and FSE T2-weighted scans acquired on the axial and sagittal planes. In all patients, the transverse diameter, the shape and the section surface of the lesions were calculated on the axial planes at different levels; all these parameters were compared with those of the adjacent tendons, i.e., flexor longus ditae and flexor hallucis. Moreover, the probable presence was investigated of intratendineous signal intensity changes, of peritendineous synovial fluid and of indirect signs of PTT tear, i.e., the lack of longitudinal talonavicular alignment and the bulging of the medial navicular tubercle. According to MR results, the 14 patients were subdivided into 8 patients with type-I tears, 2 with type-II tears and 4 patients with type-III tears. The measures of healthy and injured tendons were in substantial agreement: in fewer cases, agreement was found also between symptomatic and control patients with intratendineous signal changes. Thus, the specificity of the two parameters was reduced. Finally, such indirect signs of PTT tear as a hypertrophic navicular tubercle and the lack of longitudinal talonavicular alignment exhibited good specificity, but sensitivity was barely sufficient. MR diagnoses were confirmed at surgery in 6 patients with type-II and type-III tears. In conclusion, MRI appears to be a suitable modality for recognizing and classifying PTT tears and a useful tool for the treatment and follow-up of these patients.

Adolescent↗

Genetic mutations in the K1 and K10 genes of patients with epidermolytic hyperkeratosis. Correlation between location and disease severity.

Epidermolytic hyperkeratosis (EH) is a skin disease caused by mutations in the genes encoding K1 and K10, the differentiation-specific keratins of epidermis. To explore the heterogeneity of mutations and to assess whether a correlation exists between disease severity and the extent to which a mutation interferes with keratin network formation, we determined the genetic bases of four severe incidences of EH and one unusually mild case. Two severe cases have the same mutation, K10-R156:C, at a conserved arginine that we previously showed was mutated to a histidine in two unrelated EH families. An additional severe case has a mutation six residues away, still within the amino end of the alpha-helical rod domain of K10. The other severe case has a mutation in the conserved carboxy end of the K1 rod. In contrast, affected members of the atypically mild family have a mutation just proximal to the conserved carboxy end of the K10 rod. By genetic engineering and gene transfection, we demonstrate that each mutation is functionally responsible for the keratin filament aberrations that are typical of keratinocytes cultured from these patients. Moreover, we show that the mild EH mutation less severely affects filament network formation. Taken together, our studies strengthen the link between filament perturbations, cell fragility, and degeneration.

Amino Acid Sequence↗

Effects of surgical trauma of laparoscopic vs. open cholecystectomy.

The effects of surgical trauma resulting from laparoscopic cholecystectomy and open cholecystectomy, were compared by assessing the postoperative acute phase alterations of selected plasma proteins, hormones and lymphocyte subpopulations in fifty-seven patients prior to elective cholecystectomy. Patients were prospectively randomized to undergo either laparoscopic cholecystectomy (n = 30) or open cholecystectomy (n = 27). Duration of operation and general anesthesia was similar in the two patient groups. The laparoscopic cholecystectomy patients had a shorter postoperative stay in hospital (3.1 (0.5) days vs. 7.1 (1.6) days; p < 0.001). In open cholecystectomy patients a significantly greater postoperative acute phase increase in plasma C-reactive protein (p < 0.001), cortisol (p < 0.05), and prolactin blood level (p < 0.001) was recorded. The postoperative acute phase decrease in the blood total-T-lymphocyte count (CD3 cells) and in the activated-lymphocyte count (OKDR cells) was significantly greater after open cholecystectomy (p < 0.05). These results, showing that acute phase responses are less marked after laparoscopic cholecystectomy than after open cholecystectomy, support the concept that the laparoscopic procedure is less traumatic.

Acute-Phase Reaction↗

Voltage gradient electrophoresis of nucleic acids on agarose gels.

A very simple method is described which allows the separation of DNA molecules in a wide molecular weight range (from 0.6 to about 30 kb) in the same electrophoresis agarose gel. This is based on the achievement of a voltage gradient through a simple device consisting of a Plexiglas plate placed slantwise with respect to the gel surface plane, submerged in the electrophoretic running buffer. Further applications of our system are also described.

DNA↗

Sequence analysis of the rDNA spacer of Paracentrotus lividus and observations about pre-rRNA processing. NTS sequence of Paracentrotus lividus rDNA.

We have isolated and sequenced one intergenic region and a small part of the flanking regions (18S and 26S rRNA coding regions) of the rRNA-encoding genes (rDNA) from the sea urchin Paracentrotus lividus. This region is about 3.8 Kb long. Northern blot hybridizations and S1 mapping experiments demonstrated the presence of a partially processed 21S rRNA precursor while has the same 5' terminus as the 32S primary precursor, also in developmental stages characterized by a low rate of rRNA synthesis.

Animals↗

Two-dimensional electrophoretic analysis of stress proteins in Paracentrotus lividus.

The synthesis of stress proteins in Paracentrotus lividus embryos has been analysed by two-dimensional electrophoresis following either heat shock or ZnSO4 administration. As already shown for the 70-KDa hsp (heat shock proteins) a non responsive period, that is before hatching, exists followed by a responsive period in which up to 16 hsps are synthesized after heat shock, 7 of which are also synthesized after ZnSO4 treatment. Some of them pre-existed the stress, but their synthesis increases following the stress. Only few of them accumulate in amounts detectable by silver staining. The synthesis of all these proteins depends upon RNA synthesis.

Animals↗

[Involvement of the heart valves and great vessels in homozygote familial hypercholesterolemia].

Homozygous familial hypercholesterolaemia is characterized by cutaneous xanthoma development from infancy, precocious and accelerated atherosclerosis with clinical signs of ischemic heart disease and frequent involvement of left heart valves resulting in stenosis and/or incompetence. Two cases are described of this condition, both associated with aortic stenosis. In one case mitral incompetence and thromboembolic pulmonary hypertension were also found. The mitral valve is involved in the atherosclerotic process at the level of the cusps. These become thickened and stiff. Aortic stenosis is mainly due to atheromas infiltrating the Valsalva sinuses and the ascending aorta. Pulmonary hypertension, never reported before in this disease, is probably due to concomitant atheromatosis involving the pulmonary artery with secondary fatty embolism.

Aortic Valve Stenosis↗

A method for eluting DNA in a wide range of molecular weights from agarose gels.

We have developed a simple and rapid method for recovering DNAs of a wide range of molecular weights from agarose gels. A DNA-containing gel slice is placed on a Parafilm sheet in the center of a circular (positive) electrode and covered with a drop of buffer, while a linear (negative) electrode is placed on the top of the gel and driven about 1 mm into the gel itself. When a continuous current is applied, the DNA migrates into the buffer toward the circular electrode. We have obtained almost total recovery of DNAs up to 10 kb in size. Our method may also be used, under appropriate conditions, for higher molecular weight DNAs. The yield and all the biological assays performed on the DNAs obtained by our method recommend it for routine laboratory use.

DNA↗

Sequence of a sea urchin hsp70 gene and its 5' flanking region.

We report the nucleotide sequence of a 4470-bp fragment derived from a sea urchin genomic clone containing part of a heat-shock protein 70 (Hsp70)-encoding gene. This fragment, named hsp70 gene II, contains 1271 bp of the flanking region and 3299 bp of structural gene sequence interrupted by five introns and encoding the N-terminal 371 amino acids (aa) of the protein. The 5' flanking region contains a putative TATA element, two CCAAT boxes, four heat-shock consensus sequence elements (hse) and one consensus sequence for binding of Sp1. Remarkable homologies were observed for deduced aa sequence and intron-exon organization between hsp70 gene II and rat hsc73 gene.

Amino Acid Sequence↗

Isolation, sequence, and expression of a human keratin K5 gene: transcriptional regulation of keratins and insights into pairwise control.

The mitotically active basal layers of most stratified squamous epithelia express 10 to 30% of their total protein as keratin. The two keratins specifically expressed in these cells are the type II keratin K5 (58 kilodaltons) and its corresponding partner, type I keratin K14 (50 kilodaltons), both of which are essential for the formation of 8-nm filaments. Dissecting the molecular mechanisms underlying the coordinate regulation of the two keratins is an important first step in understanding epidermal differentiation and in designing promoters that will enable delivery and expression of foreign gene products in stratified squamous epithelia, e.g., skin. Previously, we reported the sequence of the gene encoding human K14 (D. Marchuk, S. McCrohon, and E. Fuchs, Cell 39:491-498, 1984; Marchuk et al., Proc. Natl. Acad. Sci. USA 82:1609-1613, 1985). We have now isolated and characterized the gene encoding human K5. The sequence of the coding portion of this gene matched perfectly with that of a partial K5 cDNA sequence obtained from a cultured human epidermal library (R. Lersch and E. Fuchs, Mol. Cell. Biol. 8:486-493, 1988), and gene transfection studies indicated that the gene is functional. Nuclear runoff experiments demonstrated that the K5 and K14 genes were both transcribed at dramatically higher levels in cultured human epidermal cells than in fibroblasts, indicating that at least part of the regulation of the expression of this keratin pair is at the transcriptional level. When the K5 gene was transfected transiently into NIH 3T3 fibroblasts, foreign expression of the gene caused the appearance of endogenous mouse K14 and the subsequent formation of a keratin filament array in the cells. In this case, transcriptional changes did not appear to be involved in the regulation, suggesting that there may be multiple control mechanisms underlying the pairwise expression of keratins.

Amino Acid Sequence↗

Immunologic monitoring studies in advanced cancer patients treated with recombinant human gamma interferon (IFN-gamma 4A).

Thirty-nine patients with a variety of advanced malignancies were treated with recombinant IFN-gamma 4A (AMGen, specific activity 1 to 5 x 10(7) U/mg protein). IFN-gamma 4A was administered at a dose of 10-2,000 micrograms/m2/d. Following a 2-week rest, a maintenance phase was continued with injections 3 d/wk. Immunologic monitoring studies were performed on patients' peripheral blood cells before administration of IFN-gamma 4A, then on Days 15 and 90. Flow cytometric analysis was used to determine the absolute number of CD 3+, CD 4+, CD 8+, CD 19+, and CD 16+ cells using a panel of monoclonal antibodies. Natural killer (NK) cell function was assayed by monitoring lysis of the K562 cell line in the Cr51 release assay. Changes from baseline were observed on Days 15 and 90 in all parameters studied, although the ratio of helper to suppressor cells seemed to remain within the normal range. Whereas there were no substantial changes in CD 3+ and CD 4+ cells on Day 15, IFN-gamma 4A had an enhancing effect on CD 8+, CD 19+, and CD 16+ cells. This trend continued at Day 90 only for CD 19+ and CD 16+ cells at the higher dose levels. An increase in functional NK cell activity at Day 15 was less noted on Day 90. Comparison of intravenous (IV) to intramuscular-subcutaneous (IM-SC) administration showed differences in the effect on lymphocyte subpopulations at 450 and 1,000 micrograms. The effect of IFN-gamma 4A on the equilibrium among lymphocyte subpopulations and the possibility of its role in combination therapy with other biologic response modifiers are discussed.

Antigens, CD↗

Stress proteins by zinc ions in sea urchin embryos.

In Paracentrotus lividus embryos, treatment with zinc ions induces the synthesis of the two major stress proteins with the same molecular weight as those induced by heat shock. The developmental stages responsive to zinc ion treatment are the same as those responsive to heat shock. However, zinc treatment induces a longer lasting synthesis of the stress proteins, and, unlike heat shock, does not induce thermotolerance and does not inhibit synthesis of the bulk proteins.

Animals↗

Isolation and characterization of a sea urchin hsp 70 gene segment.

Three clones containing Paracentrotus lividus sea urchin DNA sequences which cross-hybridize to Drosophila heat shock protein (hsp) 70 gene were isolated. The sequence arrangements in the three cloned DNA inserts were compared by restriction and cross-hybridization analysis. The results showed that they contain four different genes related to one Drosophila hsp 70 gene. One of these genes was subcloned, and two of the isolated fragments were shown to hybridize to genomic DNA and to RNA from heat-treated sea urchin embryo.

Animals↗

A phase I trial of recombinant human gamma interferon (IFN-gamma 4A) in patients with advanced malignancy.

We report a Phase I study in 39 cancer patients of the tolerance and biologic activity of 47 intravenous (i.v.), intramuscular (i.m.), and subcutaneous (s.c.) treatments with recombinant methional gamma interferon (IFN-gamma 4A) which most closely resembles the natural material produced by T lymphocytes. Patients were treated with IFN-gamma 4A 5 days a week for 2 weeks. After a 2-week rest period, patients were placed on the same dose of drug three times a week. The most common side effects--fever, chills, malaise, myalgias, and nausea and vomiting--were seen with all routes of administration. Reversible increases in hepatic transaminase and decrease in granulocytes counts were seen. The dose-limiting toxicities observed were malaise and orthostatic hypotension. The maximum tolerated dose was 500-1,000 micrograms/M2/day. The t1/2 of IFN-gamma 4A in the circulation was 20 min after i.v. injection. No blood levels were detected after i.m. or s.c. injection. Antibody against IFN-gamma 4A increased in three patients. A complete response was observed in one patient with pulmonary metastases from renal cell carcinoma.

Adult↗

Response to heat shock of different sea urchin species.

It is demonstrated that sea urchin embryos of the species Sphaerechinus granularis are able to respond to heat shock by producing heat shock proteins at the same stage as embryos of Paracentrotus lividus, i.e. after hatching. Arbacia lixula embryos are able to synthesize heat shock proteins already at the stage of 64-128 blastomeres. Embryonic survival is observed if the embryos are heated at the stages at which they can synthesize the heat shock proteins. The inhibition of the bulk protein synthesis after heating at 31 degrees C is never less than 50%.

Animals↗

Acquisition of thermotolerance in sea urchin embryos correlates with the synthesis and age of the heat shock proteins.

Preheating at 31 degrees C induces thermotolerance in Paracentrotus lividus embryos, which therefore become able to withstand 1-h treatment at the otherwise lethal temperature of 35 degrees C, and to develop normally. The acquisition of thermotolerance is positively correlated with the amount of heat shock proteins produced during the 31 degrees C treatment. Evidence is provided that the heat shock proteins, although present in the embryo for long periods after synthesis, lose their effect on thermotolerance within 3 h of the cessation of synthesis.

Acclimatization↗