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Biomedical subjects

J Bello

Publications and source records attributed to J Bello.

At least 55 records · Page 3Linked to original sources

Conformational changes in melittin upon complexation with an anionic melittin analog.

Melittin and its Glu-(7,21,22,23,24) analog upon mixing in equimolar concentrations form a hybrid oligomer with significant helical structure, in conditions in which each peptide separately adopts a largely disordered structure. The hybrid exhibits both cold- and heat-induced denaturations similar to the phenomena exhibited by proteins. The hybrid also retains significant residual structure at higher temperature, similar to the 'molten globular state' that has been suggested for protein. Melittin, at concentrations in which it forms helical tetramers, also exhibits these phenomena and may be used as a model for protein-denaturation studies.

Amino Acid Sequence↗

Effects of menadione on the cardiovascular system.

Cardiotoxic mechanisms induced by anthracyclines are not clearly determined. A possible hypothesis is free radical formation and cell damage due to the quinone part of the molecule. We have studied the effect of menadione on myocardial structure and function. The effect on the red blood cells has been also determined. Groups of rats were treated orally with increasing doses (5 mg/kg/d, increased to 20 mg/kg/d and 40 mg/kg/d in the 3rd and 5th w, respectively). Duration of treatment was 6 w. ECG and blood pressure changes and blood cell count, including Heinz-Ehrlich bodies and reticulocytes, hemoglobin and hematocrit, were determined before and after treatment weekly and every 2 w, respectively. At the end of the experiment, the hearts of 2 rats/group were processed for electron microscopy. Heart, spleen and liver weights were determined. Heart, spleen, liver and kidney were subjected to histopathological examinations. Menadione treatment did not affect growth. No significant ECG changes were obtained; only significant changes of wave amplitude were observed. Menadione caused no relevant hematological changes but there were some blood pressure alterations. Morphological changes in myocardial tissue were observed including a small disorganization of myofibrils and mitochondria crystolisis. Z-lines appear forming zigzags. There were differences in organ weights. This study showed the damage induced by menadione was less than injury induced by anthracyclines.

Animals↗

The intracolonic bypass tube for left colon and rectal trauma. The avoidance of a colostomy.

Traumatic perforations of the left colon and rectum are most frequently managed by procedures that include the formation of a colostomy. Primary repair without colostomy is much less commonly employed. We report nine patients with traumatic perforations of the left colon and rectum treated with the intracolonic bypass tube (ICBT) without concomitant colostomy. In all these patients we believe the standard treatment would have included fecal diversion. Four patients sustained blunt trauma and five sustained penetrating trauma. Healing of the colonic anastomosis occurred in all cases, and the ICBTs were passed per rectum between the tenth and nineteenth days postoperatively. On the basis of this study, we conclude that the ICBT has a role in the treatment of selected injuries of the left colon and rectum as a safe means of avoiding a colostomy.

Adult↗

Cerebral hyperemia, stroke, and transfusion in sickle cell disease.

To investigate cerebral hemodynamics in sickle cell disease (SCD), we used the 133Xenon inhalation technique of quantifying cerebral blood flow (CBF) in 67 patients. Clinical examinations and cerebral magnetic resonance imaging also were performed in all patients. Compared with age-matched healthy controls, CBF was elevated by 68% in patients, and inversely related to hematocrit. An experimental index of cerebral blood volume, pr4, was also elevated in the patients in a similar manner. Cerebral blood volume was positively correlated to CBF in SCD patients but not in controls. History of stroke and current neurologic symptoms were associated with lower flow and higher cerebral blood volume. Transfusion therapy reduced the hyperemia, the reduction being greater than expected by hematocrit elevation alone. These findings document a vasodilatory hyperemia in SCD. This dilatation may be a risk factor for ischemic distal-field infarctions, as visualized by MRI, due to a limitation of cerebrovascular reserve capacity.

Adolescent↗

Brain infarction in sickle cell anemia: magnetic resonance imaging correlates.

Brain infarction is a well-known but poorly understood complication of sickle cell disease. Seventy-three sickle cell disease patients underwent neurological examinations and high-field, heavily T2-weighted axial cranial magnetic resonance image (MRI) scanning. Eighteen of the 73 had a history of stroke, defined as an acute, focal neurological sign lasting longer than 1 hour; in the event of a convulsive onset, an MRI abnormality as a correlate was necessary. Sixteen of the 18 stroke patients demonstrated focal MRI abnormalities consistent with arterial borderzone infarctions. Fifty-five of the 73 patients had no history of stroke. Six of the 55 (11%) had focal MRI abnormalities suggesting previous subclinical stroke. Five of these lesions were in borderzone regions. The distinguishing feature in 21 of the 22 patients with MRI abnormalities was the predilection for lesions in the high cortical convexity, in the general regions of arterial borderzones between the major cerebral arteries and adjacent deep white matter. The pattern of MRI lesions suggests two pathogenetic mechanisms: (1) proximal large-vessel disease with inadequate cerebral perfusion (distal field insufficiency syndrome) and (2) distal small-vessel disease (sludging syndrome).

Adolescent↗

C-banding studies in lymphocytes from patients with tumors of the nervous system.

C-banding studies were performed on cultured peripheral blood lymphocytes from 100 patients with tumors of the nervous system and 30 controls. The classification of Patil and Lubs and the heterochromatic index (HI) of Neeley were used to evaluate the heteromorphism. No overall significant differences were found in the frequency of C-band variants when the findings in both tumoral populations and controls were compared, but we did find an excess of 9qh inversions in some groups of tumor patients. An increase in the amount of heterochromatin in patients with pituitary adenomas and high malignancy grade astrocytomas was noted.

Chromosome Banding↗

Methylated poly(L-lysine): conformational effects and interactions with polynucleotides.

Methylated lysine, arginine and histidine residues are found in a number of proteins (for example, histones, non-histone chromosomal proteins, ribosomal proteins, calmodulin, cytochrome C, etc.). We are studying the effects of methylation on the conformations of poly(lysine) and of the effects of methylation of poly(lysine) and poly(arginine) on interactions with polynucleotides. The conformational properties of epsilon-amino-methylated poly(lysine) differ from those of unmodified poly(lysine). Methylation increases resistance to thermally-induced and NaCl-induced changes in the CD spectrum. Guanidinium chloride increases (proportional to the degree of methylation) the extent of approach to the conformation in dispute as to its being a random coil or an extended helix. Methylation enhances aggregation in the helix-inducing solvent 0.5 M Ca(ClO4)2. With increasing methylation of poly(lysine), the conformation in dodecyl sulfate changes from beta, to 50% alpha, to random coil at the maximum methylation. Increasing methylation of poly(lysine) weakens the interaction with polynucleotides in respect to dissociation by salt, linearly with methyl content. Complexes of (dAdT)n.(dAdT)n with the polypeptides are increasingly stabilized to heat denaturation by progressive methylation. However, with a series of synthetic double-stranded RNA's and DNA's a more complex situation exists, Tm increasing or decreasing, depending on the base composition, sequence and type of sugar. Methylation of poly(lysine) and poly(arginine) can have opposite effects on Tm based on results with complexes with (dI)n.(dC)n. Methylated poly(lysine) affects the CD spectrum of polynucleotides, in a manner dependent on base composition and sequence. In some cases large positive or negative psi-spectra are induced, which, in the case of (dGdC)n.(dGdC)n, can be positive or negative depending on the degree of methylation of the polypeptide and the salt concentration. It is suggested that the biological effects of methylation proteins may be evoke by salt changes in the cell cycle, and that methylation can affect local interactions with nucleic acids and larger scale structure, and interactions with lipids.

Circular Dichroism↗

Purification of carboxymethylcellulose decreases toxicity of poly ICLC in mice.

The interferon inducer poly ICLC has toxic side effects; the carboxymethylcellulose (CMC) component is a possible source of this toxicity. We have purified CMC by ethanol extraction, and found that poly ICLC made with purified CMC is not significantly different in its effectiveness as an interferon inducer in mice than poly ICLC made with unpurified CMC, but is less toxic.

Animals↗

Poly ICL-CM dextran: an interferon inducer of reduced toxicity.

We have prepared soluble complexes of poly ICL-CM dextran that are as effective interferon IFN inducers, in mice and in rhesus monkeys, as poly ICLC. Toxicity testing was carried out in mice and, poly ICL-CM dextran is less toxic, in mice, than poly ICLC is.

Animals↗

Human serum digests poly(rI) X poly(rC) differently from other mammalian sera.

Using a new spectrophotometric assay, we found that human serum digests predominately (rC)n of (rI)n X (rC)n, in agreement with results of Nordlund et al. (Proc. Soc. Exp. Biol. Med., 1970, 133, 439-444) and DeClercq (Eur. J. Biochem., 1979, 93, 165-172) while rhesus monkey, cat, and rabbit sera digest primarily (rI)n. The results of Nordlund et al. also show (in agreement with our results) that human serum digests more of the (rC)n strand of (rI)n X (rC)n than rabbit serum. However, their results differ from ours, since they found that rabbit serum digests nearly equal, but small amounts of (rI)n and (rC)n. Results are discussed in relation to interferon (IFN) induction and toxicity following administration of (rI)n X (rC)n.

Animals↗

Poly ICLC induces anti-IC antibodies in mice and rabbits.

Poly ICLC is an interferon (IFN) inducer and antiviral, antitumor, radioprotective, and immunoregulatory agent. We show that administration of poly ICLC to mice and rabbits also results in the presence of anti-IC antibodies in their serum.

Animals↗

Attenuation of primary and scatter radiation in concrete and steel for 18 MV X-rays from a Clinac-20 linear accelerator.

With the increasing number of high-energy linear accelerators being installed in radiation-therapy facilities, an increasing need exists for carefully measured data concerning the shielding parameters of photon radiation in the energy range above 10 MeV. In this study, the 18 MV X-ray beam from a Varian Clinac 20 linear accelerator was employed. Transmission parameters were measured for the primary X-ray beam in concrete and steel. The tenth value layer for steel was 11.3 +/- 0.6 cm and for concrete 45.0 +/- 2.0 cm. Also measured were the transmission parameters for scattered radiation vs angle in concrete and steel.

Construction Materials↗

Conformation and aggregation of melittin: dependence on pH and concentration.

Melittin, a 26-residue peptide from bee venom, is transformed from a largely random to a largely alpha-helical conformation at elevated pH. At 3 x 10(-5) M melittin, circular dichroism spectra show a transition with a pK near 9.6. At 8 x 10(-5) M, two approximately equal transitions occur with pKs at 7.2 and 9.6. At 6 x 10(-4) M, a single transition is seen with a pK of 6.8, followed by a more gradual increase to at least pH 11. The transitions near pH 7 presumably arise from deprotonation of the alpha-amino group. When the amino groups are acetylated or succinylated, a 60% alpha-helical conformation is adopted at neutral or low pH. The acylated melittins form more stable oligomers than does native melittin.

Bee Venoms↗

Interactions of poly (N epsilon , N epsilon , N epsilon ,-trimethyllysine) and poly(lysine) with polynucleotides: circular dichroism and A-T sequence selectivity.

Complexes of (Lys) and [Lys(Me3)]n with natural and synthetic DNAs have been studied by CD as a function of ionic strength. In dilute EDTA, (Lys)n and [Lys(Me3)]n produce the same distortions to the CD spectrum of calf thymus DNA at r (peptide residue/nucleotide residue) values less than 0.6. At higher r values, the distortions are somewhat different. [Lys(me3)]n alters the conformation of some polynucleotides differently from (Lys)n under non- psi conditions. Therefore, methylation of histones may serve to alter the structure of chromatin. At low ionic strength, [Lys(Me3)]n and (Lys)n alter the viscosity of DNA to the same extent between r values of 0.0 and 1.0. In contrast to (Lys)n-DNA, at high ionic strengths, [lys(Me3)]n-DNA does not show psi - type CD spectra. (Lys)n forms psi - structures with (dA-dT)n and (dG-dC)n. [Lys(Me3)]n forms psi + structures with (dA-dT)n. Between 0.05 and 0.3 M NaCl, [Lys(Me3)]n forms psi+ structures with (dG-dC)n, while between 0.35 and 0.45 M NaCl, it forms a psi - structure with (dG-dC)n. Neither (Lys)n nor [Lys(Me3)]n forms psi structures with (dA)n.(dT)n or (dG)n.(dC)n. These results, in conjunction with the work of others on reconstitution of nucleosome-like particles from synthetic polynucleotides, suggest that the ability of DNA and histones to form nucleosomes is related to the formation of psi structures. (Lys)n binds preferentially to (dA)n.(dT)n over (dA-dT)n. [Lys(Me3)]n binds to (dA)n.(dT)n and (dA-dT)n with equal affinity.

Base Sequence↗

Thermal perturbation spectrophotometry of luliberin and model His-Trp peptides.

Thermal perturbation (TP) spectra of luliberin were measured at pH 5-8, and compared with the model chromophores N-Ac-Tyr-NH2, N-Ac-Trp-NH2, t-Boc-His-Trp-NH2, H-His-Trp-OH, Ac-His-Trp-OH, tryptophan and cyclo-[His-Trp] (all L-isomers). Between pH 5 and neutrality, the major TP extremum of the Trp3 residue of luliberin increases by about 50%. A similar effect is seen for luliberin acetylated on Tyr5. The effect with luliberin is attributed to the protonation of the His2 residue. One proposed explanation is that the protonated imidazole orients water around the nearby indole in a different way than does unprotonated imidazole. The Tyr5 residue of luliberin behaves like N-Ac-Tyr-NH2, and is considered to be well exposed to solvent. The TP spectra of N-Ac-Trp-NH2, t-Boc-His-Trp-NH2, Ac-His-Trp-OH, and cyclo-[His-Trp] are pH-independent from pH 5 to 8. The TP spectrum of H-His-Trp-NH2 has a bell-shaped pH dependence, rising from normal at pH 3.5 to above normal at pH 6, and returning to normal at pH 8. Luliberin and model peptides show that fluorescence and TP spectra of His-Trp sequences can respond differently to pH.

Dipeptides↗