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Biomedical subjects

E Bucci

Publications and source records attributed to E Bucci.

At least 91 records · Page 5Linked to original sources

Hemoglobin tetramers stabilized with polyaspirins.

Organic acids activated by esterification with 3,5-dibromosalicylate react preferentially either with the beta 82 lysines or the alpha 99 lysines of hemoglobin. The versatility and site specificity of these polysapirins and the usage of both human and bovine hemoglobins allowed the construction of a family of oxygen carriers with various P50 ranging from 10 to 50 mmHg. These derivatives are obtained in pure homogeneous form by column chromatography. They are stabilized tetramers where the dissociation into dimers is inhibited. The latest addition is Tri-(3,5,dibromosalicyl)-benzenetricarboxylate, which crosslinks both human and bovine hemoglobin across the beta subunits, decreasing the oxygen affinity of both proteins. The crosslinked hemoglobins have a normal Bohr effect, more expanded in the alkaline region, and are sensitive to chlorides but not to polyphosphates. Solutions of stabilized tetramers, infused into rats or cats up to 25-50% blood replacement, do not produce altered renal and cardiac function. In the cat isovolemic hemodilution increases cerebral flow in controls treated with albumin solutions, when an oxygen carrier is used the cerebral flow remains normal.

Animals↗

Peripheral ameloblastoma: case report.

A case of peripheral ameloblastoma, a rare odontogenic tumour, is presented. This tumour appears to differ from endo-osseous ameloblastoma by the absence of local malignancy. It exhibits a less aggressive and destructive behavior and does not invade the underlying bone. Conservative treatment of the tumour is the treatment of choice.

Aged↗

Gingival localization of fibrosarcoma of soft oral tissues: case report.

A gingival localization of fibrosarcoma of soft oral tissues was described in a 58-year-old female. Primary fibrosarcoma of the head and neck region is rare. The histological appearance of the tumour is related to its grade of differentiation. The amount of collagen is variable. The accepted treatment is radical surgery; but metastases occur frequently in the lungs.

Female↗

Hemoglobin as oxygen carrier in cell-free fluids.

The University of Maryland is studying the oxygen needs of internal organs and how these needs can be met by oxygen carriers in cell-free fluids. Once developed, cell-free oxygen carriers will have a large variety of applications including hemodilution, transfusion therapy, organ preservation, and cancer therapy.

Animals↗

Discontinuous release of heat at successive steps of oxygenation in human and bovine hemoglobin at pH 9.0.

We have measured the temperature dependence of the oxygen-binding isotherms of human and bovine hemoglobin at pH 9.0 in 0.1 M borate buffer. In both hemoglobins the ionization of the Bohr protons is finished at this pH; therefore, their heat does not interfere with the measurements. Two sets of curves have been obtained, which have been analyzed by either singular or global procedures for estimating the enthalpy changes of subsequent steps of oxygenation. The data indicate that in human hemoglobin the reaction with oxygen is enthalpy driven for steps 1, 2, and 4 while it is entropy driven for step 3. In bovine hemoglobin this phenomenon is even more evident: steps 2 and 4 are enthalpy driven while steps 1 and 3 are entropy driven. The discontinuous distribution of heat at subsequent steps of oxygenation suggests that the T to R transition in hemoglobin is not a monotonic process and involves conformations with novel characteristics.

Animals↗

Recombinant interleukin-2 and lymphokine-activated killer cells in renal cancer patients: II. Characterization of cells cultured ex vivo and their contribution to the in vivo immunomodulation.

Peripheral blood mononuclear cells, obtained from patients with renal cell cancer and cultured ex vivo, exhibit high natural killer (NK) and lymphokine-activated killer (LAK) activity (also against allogeneic fresh tumour cells), which is transcribed into the hosts' immune status after reinfusion. Phenotypic analysis shows a slight increase in the percentage of CD56+ and CD8+ lymphocytes, while CD4+ lymphocytes decrease slightly. As a sign of activation an increase of cells expressing DR and CD25 antigens is observed. At the peripheral blood level, mononuclear cells show an increase, compared to basal values, of NK and LAK activity, especially at the end of the first infusion cycle. Phenotypic analysis of the patients' PBMC shows a decrease of CD3+CD4+ T lymphocytes and an increase of NK cells (CD3-CD56+CD16+) and of cells expressing activation markers (DR and CD25), particularly evident by the end of the second infusion cycle. Finally, in addition to the changes induced by IL-2 alone, reinfusion of incubated cells results in an activation of CD56+ and LeuM3+ cells.

Antigens, CD↗

Intravascular retention and renal handling of purified natural and intramolecularly cross-linked hemoglobins.

Plasma half time of unmodified hemoglobin (UHb) and two intramolecularly cross-linked hemoglobins (alpha alpha XL and beta beta XL) was measured in anesthetized rats after an intravenous bolus of 20 mg.100 gm.-1 To rule out the possibility that differences among plasma half times might be caused by differences in acute effects on renal excretory function, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured simultaneously with plasma half time. Experiments were also done to determine whether higher doses (60 to 100 mg-1.100 gm-1) of these compounds had a delayed effect (48 hours) on GFR or ERPF. Massive urinary excretion of UHb occurred; however, only 1% of the alpha alpha XL and none of the beta beta XL was excreted. Plasma half time of alpha alpha XL and beta beta XL averaged 3.3 hours, or four times longer than UHb. In no case did a decrease in GFR or ERPF occur. Instead, a transient increase in GFR, ERPF, urine flow, and systemic blood pressure was seen. Similar increases occurred after albumin administration, suggesting expansion of vascular volume as the initiating factor. Renal functions at 48 hours after 60 to 100 mg.100 gm-1 of UHb, alpha alpha XL or beta beta XL were not different from control (albumin). Intratubular hemoglobin casts or intravascular precipitates were not evident in acute or 48-hour studies. At 48 hours Perls' staining material was found in one alpha alpha XL specimen at 3 hours after administration. Perls' staining material was present in renal tubule cells in all but the albumin-treated kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Bovine hemoglobin pseudo-crosslinked with mono(3,5-dibromosalicyl)-fumarate.

Under oxygenated conditions bovine hemoglobin reacts with mono(3,5-dibromosalicyl)-fumarate which specifically acylates the EF5 lysines in the beta-cleft of the protein. The chemical modification introduces in the molecule a pseudo-crosslink which hinders the dissociation of the hemoglobin molecule into dimers. Retention time in circulation of the chemically modified bovine hemoglobin, measured in the rat, is increased fivefold with respect to untreated bovine hemoglobin. The oxygen affinity at 37 degrees C and at pH 7.4, has a P50 = 5.4 kPa and a value of n = 1.9. Under the same experimental conditions the oxygen affinity is not sensitive to anions and polyanions whereas it is sensitive to CO2. The Bohr effect is shifted toward the alkaline pH range by 0.5-1: the maximum number of protons released is 1.5/tetramer, similar to normal bovine hemoglobin (1.8 protons/tetramer). Analysis of the binding isotherms, using the two-state Monod-Wyman-Changeux model and fixing the value of the allosteric constant L = 10(5), shows that the oxygen affinity of the T structure is not modified, and that the low oxygen affinity of the system is due to a decrease of the oxygen affinity of the R structure. Analysis using the sequential Adair model shows a modification of the overall binding constants and suggests a redistribution of the intermediate species of oxygenation.

Animals↗

Perturbation of molecular species distribution in steady states supported by a flow of energy. Models analogous to Ca2(+)-dependent ATPase and phosphorylase b.

When an allosteric macromolecular system is capable of existing in two conformations, both of which may be converted into energy-storing forms by the binding of a substrate or by the absorption of radiant energy, then a kinetic process may occur, such as an enzymic conversion of the substrate into products, which liberates energy and selectively depletes one or more of the forms of the macromolecule. Upon a continuous supply of energy, a steady state, or pseudoequilibrium, is reached during which the selective depletion of molecular species results effectively in a directional flow of energy through the system. This perturbs the distribution of the various molecular species. This effect may simulate both positive and negative binding cooperativity, and mimic the presence of multiple binding sites with different affinities even in monomeric, monovalent systems. Specific model systems are presented analogous to the transport of Ca2+ by sarcoplasmic reticulum and the allosteric behavior of phosphorylase b.

Allosteric Regulation↗

Effect of temperature on oxygen affinity and anion binding of bovine hemoglobin.

Measurements of oxygen binding to bovine hemoglobin have been carried out over the temperature range 15-37 degrees C at pH 7.33. The standard enthalpy of oxygenation after correction for the heat of oxygen solution and of the Bohr protons is found to be -7.1 or -7.2 kcal/mol in the presence of 0.1 M chloride or bromide, respectively. This value is well below the -14.4 kcal/mol determined for human hemoglobin under identical experimental conditions. As reported by Fronticelli et al. (C. Fronticelli, E. Bucci and A. Razynska, J. Mol. Biol. 202 (1988) 343), the preferential binding of anions by bovine hemoglobin recognizes the various halides. Measurements at various temperatures reveal that this is true only above 25 degrees C. The halide recognition and the less exothermic enthalpy of oxygenation of bovine hemoglobin are probable due to oxygen-linked hydrophobic effects that are larger in bovine than in human hemoglobin.

Animals↗

Generalized juvenile periodontitis: report of a familial case followed for 5 years.

The case of a family, followed for 5 years and showing an exceptionally high prevalence of Generalized Juvenile Periodontitis (GJP), is presented. Two siblings were affected by a severe form of GJP meanwhile the dycorial twin of one was periodontally healthy. Both the affected siblings showed infection by Actinobacillus actinomycetemcomitans (Aa), but only one presented a reduced chemotaxis of the peripheral PMNs. The dycorial twin consistently displayed a freedom from Aa and a reduction in the peripheral PMNs chemotaxis. The extraction of the compromised teeth in the two affected siblings has been followed by colonization of new sites by Aa; only repeated administration of systemic tetracyclines seems to protect the subjects from colonization of other sites. These findings may contribute to the understanding of the etiology, pathogenesis, and therapy of juvenile periodontitis.

Actinobacillus↗

[A clinical study of the therapeutic activity and tolerance of nimesulide in a suppository formulation in oral medicine].

A double-blind versus placebo clinical study has been carried out in order to assess the antiinflammatory and analgesic activity of nimesulide suppositories in pain-inflammatory pathologies of odontostomatological nature. Forty-four patients aged between 18 and 62 were recruited for the purpose and assigned at random to treatment with nimesulide or placebo for a minimum period of 3 days. Treatment with nimesulide reduced both the pain and the tumefaction due to the inflammatory pathology more rapidly and, by the 3rd day of treatment led to complete remission of the symptomatology. Tolerability of nimesulide was excellent.

Adolescent↗

[Beta-thalassemia and its orodental implications. I. The clinical considerations].

The paper reviews the literature on oral modifications presented by subjects affected by beta-thalassemia, an hereditary hemopathy present in significant numbers in some areas of Italy. Following a description of the clinical characteristics of the disease, the paper focuses on the genetic alterations leading to the hemopathy and their implication in the onset of the thalassemic state.

Globins↗

[Beta-thalassemia and its orodental implications. II. A clinical study].

The paper reports the findings of a study of 46 subjects affected by beta-thalassemia major who underwent periodic transfusion therapy. A reduced incidence of the caries process was observed, above all in subjects treated from the first months of life. After a short review of the main problems posed by these patients during dental treatment, the Authors propose a course of preventive antibiotic treatment to be carried out before the start of dental work.

Adolescent↗

Pseudo cross-link of human hemoglobin with mono-(3,5-dibromosalicyl)fumarate.

The reaction of human oxyhemoglobin with mono(3,5-dibromosalicyl)fumarate, produces a derivative specifically acylated at the two lysines beta 82, which can be purified with a 70% yield. The oxygen affinity of this derivative at 37 degrees C at pH 7.4, 0.1 M Cl- is of 12 mm Hg, and is not affected by organic phosphate. In the presence of 5% CO2, the oxygen affinity decreases to 25 mm Hg. In all cases the cooperativity is lowered, with a value of n in the Hill plots near 2. Sedimentation velocity measurements indicate that, contrary to normal hemoglobin, this derivative fails to dissociate into dimers upon exposure to pH 5.5. The stability of the tetrameric structure is probably due to a modification of the beta-beta interface, resulting from electrostatic and hydrophobic interactions introduced in the beta cleft by the fumaryl residues. These new interactions are probably the origin of a new reverse Bohr effect group at alkaline pH. Consistent with the stabilization of the tetrameric structure, the half-time of retention of this compound in the rat is increased 4-fold with respect to that of normal hemoglobin. These characteristics cast a favorable light on the usage of this compound as an oxygen carrier in transfusional and perfusional fluids.

Amino Acids↗

Local phenomena and distribution of molecular species during the unfolding of heme-free myoglobin in the presence of GdnHCl and urea as seen by time-resolved fluorescence spectroscopy.

We have used time-resolved fluorescence spectroscopy for following the unfolding of apomyoglobin in urea and guanidine hydrochloride (GdnHCl). The data have been compared with those obtained using classical techniques such as CD and steady-state emission spectroscopy. Both the average intensity of the lifetimes and the size of the librational cone of the fluorophores, as measured by time-resolved fluorescence, increased with denaturant concentration and their changes largely preceded the modifications detectable with CD and the shift of the maximum of emission spectra. The data indicate that the changes in the local environments of the tryptophans were completed when the global modification monitored by CD and the emission spectra was still minimal. This suggests that an initial event in the denaturation of apomyoglobin is localized at the tryptophan residues. The correlation times of native apomyoglobin showed the rotational diffusion characteristics of a rigid rotor. In 3.6 M GdnHCl and 7.5 M urea, where the secondary structure is practically absent, the correlation times of the two systems became very short, as expected from the motion of a flexible polymer. In GdnHCl, under conditions of partial unfolding, it was not possible to detect the presence of native totally folded molecular species.

Apoproteins↗