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Biomedical subjects

A Borges

Publications and source records attributed to A Borges.

At least 55 records · Page 3Linked to original sources

Chemoprevention by melatonin and combined melatonin-tamoxifen therapy of second generation nitroso-methylurea-induced mammary tumours in rats.

Melatonin, an indole of pineal origin, is known to have an oncostatic effect on carcinogen-induced rat mammary tumours. We have assessed for the first time, the efficacy of melatonin alone and in combination with a sub-optimal dose of tamoxifen, a partial oestrogen antagonist, on N-nitroso-N-methylurea-induced rat mammary tumours. Both these agents were administered to Sprague-Dawley rats following excision of the primary tumours. Melatonin (200 micrograms/day/rat) at the given dose level could significantly suppress the appearance of second generation mammary tumours and the latency period of tumour appearance was also significantly increased (P < 0.001) as compared to vehicle-treated animals. Tamoxifen (60 micrograms/week/rat) does not suppress the development of second generation mammary tumours. Co-administration of melatonin and low dose of tamoxifen had no additive or synergistic effect on the prevention of second generation of mammary tumours. The results warrant the clinical evaluation of melatonin for chemoprevention and adjuvant therapy.

Animals↗

[Abnormal origin of left coronary artery from pulmonary artery].

OBJECTIVE: To assess the frequency and severity of the anomalous origin of the left coronary artery (ALCA) from the pulmonary artery (PA). DESIGN OF THE STUDY: Prospective study of case series between March 1991 and December 1994. SETTING: Referral-based Paediatric Cardiology Department of a Tertiary Care Center. PATIENTS AND METHODS: Five consecutive patients (pts) with anomalous origin of the LCA from the PA; there were three infants aged 4 months and two children one 8 year and one 9 year old. There were three girls and two boys. All pts had clinical and 2D-echo and Doppler investigation prior to cardiac catheterization (CC). Indication for CC was based in the association of symptoms and signs of myocarditis or dilated cardiomyopathy of acute or subacute onset and electrocardiographic (ECG) signs of ischemia in infants. In older patients (pts) diagnosis was suspected mainly from ECG. During CC in all pts, aortograms and when necessary selective coronary angiograms were performed. Surgical correction was performed in all children. In two pts stress exercise ECG and stress Thallium studies before and after surgery were performed. RESULTS: two pts had "adult" an three had "infantile" type of ALCA from the PA. CC was performed and diagnosis was confirmed at surgery in all cases. In one child, correct diagnosis was made by ECO prior to CC and in one case LCA to PA fistula was suspected on Colour-Doppler study. No complications were attributed to CC. Several types of surgery were performed: reimplantation of the ALCA from the PA to the aorta (three pts); tunnel connection of the aorta to the ALCA via the PA (one pt) and left internal mammary to LCA anastomosis (one pt). Two infants died intraoperatively due to extensive myocardial infarction and poor left ventricular function. All the three survivors are asymptomatic after a mean follow up of 34 months. Two oldest pts are currently in New York Heart Association functional class I with normal ECG and improved myocardial perfusion on Thallium scan despite almost total occlusion of LCA at the site of implantation in the aorta as diagnosed on coronary angiogram. CONCLUSIONS: ALCA from PA is associated with major morbidity and mortality. Diagnosis should be suspected in pts with unexplained myocardial ischemia on ECG and even more if it is associated to clinical signs of dilated cardiomyopathy or myocarditis. Careful assessment on ECO and pulsed Doppler and colour flow mapping should make the diagnosis in most cases. Although surgery can be performed based only on ECO diagnosis, we strongly advise for angiography in all cases as in our experience there are false negative diagnosis by ECO. Preoperative Thallium studies can be useful for the selection of the type of surgery as pts with very little viable myocardium will not survive the establishment of a direct systemic to coronary blood flow and may be candidates for heart transplantation.

Abnormalities, Multiple↗

[The acquired immunodeficiency syndrome, hypertrophic myocardiopathy and multivalvular infectious endocarditis. Apropos a clinical case].

We present a clinical case of a 33 years old young male, gypsy, intravenous drug abuser with heroine and cocaine and AIDS diagnosis. The clinical anamnesis was mainly fever and systolic heart murmur in a clinical scenario of AIDS. The two-dimensional echocardiographic study was clearly diagnostic of an hypertrophic obstructive cardiomyopathy of the left ventricle. This study showed also the presence of multiple vegetations of the mitral, aortic and pulmonic valves in a clinical setting of an acute Streptococcus Viridans infective endocarditis. In this case report we discuss the incidence of this type of multiple cardiac lesions and particularly the presence of this specific pathogenic agent in this high risk group of patients with intravenous drug abuse and systemic immunosuppression. We pointed out the rarity of these findings of left side valvular vegetations associated with this type of cardiomyopathy and the different factors related to infective endocarditis.

AIDS-Related Opportunistic Infections↗

Patterns of neuropsychological deficit in cases of schizophrenia spectrum disorder with and without a family history of psychosis.

This study was designed to identify the types of neuropsychological deficits that are unique to familial and nonfamilial forms of schizophrenia. Seventy-two patients who met Research Diagnostic Criteria for schizophrenia or schizoaffective disorder, mainly schizophrenic, were divided into two groups on the basis of the presence or absence of a family history of psychosis. The two groups were then compared for differences on six neuropsychological parameters as well as for differences in psychotic symptoms. Multivariate analyses indicated that schizophrenic patients with a family history of psychosis showed significantly higher levels of overall neuropsychological deficit and significantly greater deficits on tests of motor-control and abstraction and problem-solving. Factor analyses indicate that schizophrenic patients with a family history of psychosis show a pattern of specific neuropsychological deficits, while schizophrenic patients without a family history show a pattern of more consistent cognitive deficits. The results of this study indicate that recent-onset schizophrenic patients with and without a family history of psychosis show distinctly different patterns of neuropsychological dysfunction. These data suggest that abnormalities in the dorsolateral prefrontal cortex and nonprimary motor areas may be associated with an increased familial risk for psychotic disorder.

Adult↗

Household bleaches based on sodium hypochlorite: review of acute toxicology and poison control center experience.

Bleaches based on solutions of sodium hypochlorite (NaOCl) are widely used in the household to disinfect and clean hard surfaces and to bleach the laundry. A review of both published and unpublished toxicological data is presented. In addition, the results of a survey of human accidents with hypochlorite bleaches by the Poison Control Centers of France, Italy, Belgium, Greece, Turkey, Spain and Portugal for the period 1989-1992 are presented. The data show that acute accidental exposure to household bleach in use or in foreseeable misuse situations results, in the great majority of the cases, in minor, transient adverse effects on health, with no permanent sequelae. Ingestion is the most frequent route of exposure, followed by inhalation of gases evolved by mixing sodium hypochlorite bleach with acid or alkaline products. All evidence presented confirms the normal safety profile of hypochlorite-based bleaches to be similar to that of other 'generally recognized as safe' household products.

Accidents, Home↗

Trypanosoma cruzi trypanothione reductase. Crystallization, unit cell dimensions and structure solution.

We have reproducibly crystallized recombinant trypanothione reductase from Trypanosoma cruzi. Yellow tetragonal crystals in the shape of elongated prisms have unit cell dimensions of a = 92.8 A, c = 156.6 A, Laue symmetry of 4/m and are suitable for a detailed structural analysis. Diffraction data to 2.7 A resolution have been recorded using synchrotron radiation at the Daresbury laboratory. The structure has been solved by molecular replacement calculations using this synchrotron data and our previously determined Crithidia fasciculata enzyme structure as a search model. The space group has been identified as P4(3) with a homodimer of approximate molecular mass of 108 kDa in the asymmetric unit. Diffraction beyond 2.5 A has been recorded when large freshly grown crystals are exposed to X-rays. Refinement of the structure is in progress.

Animals↗

Giant cell fibroblastoma.

A report of a 1 1/2-year-old male child diagnosed as a case of giant cell fibroblastoma is described and the available literature on this neoplasm is reviewed. The tumor consists of a mixture of spindle cells and multinucleated giant cells in a myxoid or collagenous background. The pathological findings and clinical course suggest that these tumors be classified with fibromatoses of childhood. Removal of the tumor with wide excision is sufficient and these patients do not require any form of chemotherapy.

Fibroma↗

[Fetal echocardiography. The results of a 3-year study].

During the last three years (July 89 to July 92), 875 fetal echocardiographic studies were performed, at a mean gestational age of 26 +/- 6.5 weeks (12 to 40 weeks), with the following main referral indications: family history of congenital heart disease 23%; advanced maternal age 13%; fetal arrhythmia 10%; amniotic fluid abnormalities 8%; fetal malformations 7%; diabetes 6%; four chamber view changes 4%. There were 15 twin pregnancies, two of them thoracopagus. The referral patterns with higher percentage of cardiac pathology were: abnormal four chamber view 56%; fetal chromosomal anomalies 50%; omphalocele 33%; twin pregnancy 33%; IUGR 29%; arrhythmias 20%. The referral patterns with lower percentage of cardiac pathology were: congenital heart disease in the family 0.2%; maternal risk 2%; amniotic fluid volume alterations 2%. The diagnosis of congenital heart disease was made in 37 fetus (4.2%), with the following most frequent: 9 cases with the atrioventricular septal defect, 5 cases with ventricular septal defect, 5 cases with hypoplastic left heart syndrome and 5 cases with tricuspid valve abnormalities. From a total of 78 referred fetal arrhythmias, 25 were confirmed, 20 being ectopic beats without structural heart disease, 3 with tachycardia, and 2 with bradycardia. One newborn with tachycardia and Ebstein's disease died, and the fetus with AV block and left atrial isomerism died in utero. The treatment and follow up of the remaining cases with heart disease are described. The whole mortality in the cases with heart pathology was 65%.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗

Rationally designed selective inhibitors of trypanothione reductase. Phenothiazines and related tricyclics as lead structures.

Trypanothione reductase, an essential component of the anti-oxidant defences of parasitic trypanosomes and Leishmania, differs markedly from the equivalent host enzyme, glutathione reductase, in the binding site for the disulphide substrate. Molecular modelling of this region suggested that certain tricyclic compounds might bind selectively to trypanothione reductase without inhibiting host glutathione reductase. This was confirmed by testing 30 phenothiazine and tricyclic antidepressants, of which clomipramine was found to be the most potent, with a K(i) of 6 microM, competitive with respect to trypanothione. Many of these compounds have been noted previously to have anti-trypanosomal and anti-leishmanial activity and thus they can serve as lead structures for rational drug design.

Amino Acid Sequence↗

Tuberculosis of the pancreas: report of three cases.

Three cases of pancreatic tuberculosis are described. The first patient presented with abdominal pain, weight loss, anorexia, vomiting, hepatomegaly, and mass in the head of the pancreas, on computerized tomographic (CT) scan. The second patient presented with low grade fever, anorexia, and weight loss, and was investigated for gallbladder disease. The third patient presented with obstructive jaundice and mass lesion in the head of the pancreas. Two patients underwent laparotomy for suspected pancreatic tumors. The findings of pancreatic disease was incidental during laparotomy in the second patient. The histopathology revealed caseating granuloma in all of them. The first patient responded well to treatment, and the second patient stopped treatment after 2 months and is well. The third patient is being followed. If malignancy can be ruled out, tuberculosis should be considered in relevant geographic areas, and a tissue diagnosis should be made.

Adult↗

Cloning and sequence analysis of the genes encoding the dihydrolipoamide acetyltransferase and dihydrolipoamide dehydrogenase components of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus.

A 2641-bp EcoRI fragment of DNA that encodes the C-terminal part of the dihydrolipoyl acetyltransferase (E2) component and the dihydrolipoamide dehydrogenase (E3) component of the pyruvate dehydrogenase complex of Bacillus stearothermophilus has been cloned in Escherichia coli. Its nucleotide sequence was determined. A 705-bp truncated open reading frame was located at the 5'end of the insert which, together with the 588-bp truncated open reading frame at the 3' end of another EcoRI fragment of B. stearothermophilus DNA previously cloned and sequenced [Hawkins, C. F., Borges, A. & Perham, R. N. (1990) Eur. J. Biochem. 191, 337-446], was identified as the gene, pdhC, encoding the E2 polypeptide chain. Direct sequence analysis of the purified E2 chain confirmed that the two EcoRI fragments are adjoining in the B. stearothermophilus genome. The E3 gene, pdhD, begins just 4 bp downstream from the stop codon of the pdhC gene. The amino acid sequences deduced from the pdhC and pdhD genes correspond to proteins of 427 amino acids (E2, Mr 46,265) and 469 amino acids (E3, Mr 49,193), respectively. Both genes are preceded by potential ribosome-binding sites and the E3 gene is followed by a stemloop structure characteristic of rho-independent transcription terminators. The B. stearothermophilus E2 and E3 chains exhibit substantial sequence similarity with the corresponding subunits of other 2-oxo-acid dehydrogenase multienzyme complexes. The cloning and sequence analysis described here complete the description of the gene cluster (pdhA, B, C and D) which encodes the B. stearothermophilus pyruvate dehydrogenase multienzyme complex.

Acetyltransferases↗

Cloning and sequence analysis of the genes encoding the alpha and beta subunits of the E1 component of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus.

A 4175-bp EcoRI fragment of DNA that encodes the alpha and beta chains of the pyruvate dehydrogenase (lipoamide) component (E1) of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus has been cloned in Escherichia coli. Its nucleotide sequence was determined. Open reading frames (pdhA, pdhB) corresponding to the E1 alpha subunit (368 amino acids, Mr 41,312, without the initiating methionine residue) and E1 beta subunit (324 amino acids, Mr 35,306, without the initiating methionine residue) were identified and confirmed with the aid of amino acid sequences determined directly from the purified polypeptide chains. The E1 beta gene begins just 3 bp downstream from the E1 alpha stop codon. It is followed, after a longer gap of 73 bp, by the start of another but incomplete open reading frame that, on the basis of its known amino acid sequence, encodes the dihydrolipoyl acetyltransferase (E2) component of the complex. All three genes are preceded by potential ribosome-binding sites and the gene cluster is located immediately downstream from a region of DNA showing numerous possible promoter sequences. The E1 alpha and E1 beta subunits of the B. stearothermophilus pyruvate dehydrogenase complex exhibit substantial sequence similarity with the E1 alpha and E1 beta subunits of pyruvate and branched-chain 2-oxo-acid dehydrogenase complexes from mammalian mitochondria and Pseudomonas putida. In particular, the E1 alpha chain contains the highly conserved sequence motif that has been found in all enzymes utilizing thiamin diphosphate as cofactor.

Acetyltransferases↗

Isolation and characterization of toxic proteins from the venom of the Venezuelan scorpion Tityus discrepans (Karsch).

Four toxic, electrophoretically homogeneous proteins were isolated by ion-exchange chromatography on CM-cellulose-52 from the venom of the scorpion Tityus discrepans (range North Central Venezuela), named TdIV, TdV, TdVIII and TdIX. Component TdVIII, with 56 amino acid residues and mol. wt 6140 was the most toxic by i.p. injections into mice and had an intracisternal LD50 of 7.9 micrograms protein/kg body weight. Amino acid compositions of components TdIV and TdV were very similar, suggesting that they could be highly homologous proteins, although presumably contaminated one by the other. A fifth component, named TdIII, non-toxic by i.p. injections, was also isolated in homogeneous form. The i.v. and intracisternal LD50 values of the whole T. discrepans venom were 2.5 mg/kg and 16.0 micrograms/kg, respectively.

Amino Acids↗

A common structural motif in thiamin pyrophosphate-binding enzymes.

The amino acid sequences of a wide range of enzymes that utilize thiamin pyrophosphate (TPP) as cofactor have been compared. A common sequence motif approximately 30 residues in length was detected, beginning with the highly conserved sequence -GDG- and concluding with the highly conserved sequence -NN-. Secondary structure predictions suggest that the motif may adopt a beta alpha beta fold. The same motif was recognised in the primary structure of a protein deduced from the DNA sequence of a hitherto unassigned open reading frame of Rhodobacter capsulata. This putative protein exhibits additional homology with some but not all of the TPP-binding enzymes.

Amino Acid Sequence↗

Amino acid sequence analysis of the lipoyl and peripheral subunit-binding domains in the lipoate acetyltransferase component of the pyruvate dehydrogenase complex from Bacillus stearothermophilus.

The pyruvate dehydrogenase multienzyme complex from Bacillus stearothermophilus comprises a structural core, composed of 60 dihydrolipoamide acetyltransferase (E2p) subunits, which binds multiple copies of pyruvate decarboxylase (E1p) and dihydrolipoamide dehydrogenase (E3) subunits. After limited proteolysis with chymotrypsin, the N-terminal lipoyl domain of E2p was excised, purified and sequenced. The residual complex, which remained assembled, was then digested with trypsin under mild conditions. This treatment promoted complete disassembly of the complex and the various components were separated by gel filtration and h.p.l.c. A folded fragment of E2p containing about 50 amino acid residues was identified as being responsible for binding the E3 subunits, although, unlike the corresponding region of the E2p or E2o chains of the pyruvate dehydrogenase or 2-oxoglutarate dehydrogenase complexes from Escherichia coli, the fragment also bound E1p molecules. Further peptide purification and sequence analysis allowed the determination of the first 211 amino acid residues of the B. stearothermophilus E2p chain, thus providing the complete primary structure of the lipoyl domain, the E1p/E3-binding domain and the regions of polypeptide chain, probably highly flexible in nature, that link the domains to each other and to the inner-core (E2p-binding) domain. Several of the proteolytically sensitive sites were also identified. The sequence of the B. stearothermophilus E2p chain shows close homology with the sequences of the E2p and E2o chains from E. coli, although significant differences in structure are apparent. Detailed evidence for the sequence of the peptides obtained by limited proteolysis and further chemical and enzymic cleavages have been deposited as Supplementary Publication SUP 50142 (11 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 6BQ, U.K., from whom copies may be obtained as indicated in Biochem. J. (1988) 249, 5.

Acetyltransferases↗

Nasopharyngeal carcinoma in India: end-result analysis (1980-1984).

One hundred fifty patients with nasopharyngeal carcinoma were treated at the Tata Memorial Hospital from January 1980 to December 1984. Lymphoepithelioma was the most common histologic subtype. Advanced disease in stages III and IV was seen in 22.66% and 72% of the patients, respectively. Complete remission was obtained in 80 of 120 patients (66.66%) with radiation alone and in 19 of 30 patients (63.3%) who received preradiation chemotherapy and radiation. Age, sex, and histology did not influence the rate of complete remission. The N0-1 nodal status group had a significantly better response of 81% and 36% survival, as compared with the N2-3 group with a 55% response and 20% survival. Only 30 of those who received radiation alone and 10 of those who received preradiation chemotherapy are disease-free for a median period of 24 months. Twenty-six relapses have occurred within a median period of 12 months. The 5-year actuarial disease-free survival is 13%. This indicates the need for an early diagnosis and combined aggressive treatment to improve survival.

Adolescent↗