Community service day '92.
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Biomedical subjects
Publications and source records attributed to F Miranda.
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From April 1985 to November 1990, 12 patients with adenocarcinoma in a Barrett's esophagus, all of them men, with a median age of 62 years (range, 46 to 79 years), were operated by transhiatal esophagectomy and were submitted to a periodic follow-up. Dysphagia was the main symptom. Preoperative investigations included esogastroscopy and CT-scan of the abdomen and thorax in all patients. Esophageal endosonography was performed in the last 4 cases and MRI in one case. All patients recovered postoperatively and were discharged from hospital. The resected specimens were staged according to Rosenberg et al.'s classification: stage 1, 3 patients, stage 2, 2 patients, stage 3, 6 patients, stage 4, 1 patient. An anastomotic stricture occurred in 4 patients and was treated successfully by endoscopic dilatation. Five patients died during the follow-up period. Seven patients are alive without evidence of recurrence. Transhiatal esophagectomy appears to be the procedure of choice for adenocarcinoma arising from Barrett's esophagus.
In BALB/c mice, acute retinal necrosis occurs in the uninoculated eye 8 to 10 days following uniocular anterior chamber inoculation of the KOS strain of herpes simplex virus type 1 (HSV-1). Retinitis in the uninjected eye can be prevented if HSV-1-specific immune effector cells that have been restimulated with virus in vitro are administered intravenously within 1 day of anterior chamber inoculation of virus. We explored further the mechanism of protection afforded by these activated immune effector cells. The results of our studies revealed that optimal protection from retinitis required in vitro restimulation, since infusion of 50 x 10(6) HSV-1-primed but nonrestimulated cells could not protect as well as 10 x 10(6) activated cells. Analysis of both restimulated and nonrestimulated cells showed that only in vitro-restimulated cells were cytotoxic to HSV-1-infected syngeneic target cells. From these studies, we concluded that the ability to kill virus-infected target cells contributed to optimal protection achieved by intravenous administration of activated immune effector cells. Furthermore, T-cell subset depletion of activated immune effector cells demonstrated that both L3T4+ and Lyt-2+ T cells in the transfer inoculum contributed to protection. Additional studies revealed that although the transferred immune effector cells reached the injected eye within 24 h, virus replication in the injected eye was not affected. In the uninjected eye, virus titers were low, consistent with protection of this eye from retinitis. Taken together, the virus recovery results suggest that the interaction of virus with intravenously administered HSV-1-specific immune effector cells which limits virus spread and/or replication of virus probably occurred within the central nervous system and prevented the second wave of virus from entering the uninoculated eye.
The activity of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the hexose monophosphate (HMP) shunt pathway, was measured in both normal and tumoral larynx tissues from normal and G6PD deficient subjects. Significant increases of this enzymatic activity were found in tumoral tissues of both normal and G6PD deficient subjects, who were characterized by very low levels of G6PD activity in erythrocytes as well as in larynx tissue.
A mildly dyslexic boy of 11 years, with no neurological deficit or history of epileptic seizures, had marked hypersomnia for 2 years, which was most pronounced in the morning hours. Repeated EEG studies and power spectral analysis revealed simultaneous posterior alpha rhythm and sleep patterns (spindles, vertex waves, K complexes) over vertex and frontocentral regions, while the patient was behaviorally awake. Bilateral synchronous anterior spikes were frequently noted in association with sleep patterns. A polysomnogram over 24 h confirmed excessive sleep, night and day (especially morning hours) and there was evidence of a large REM sleep percentage (on EMG and EOG basis) while the EEG had predominantly non-REM sleep patterns. Special neurotransmitter studies were performed in view of a presumed disturbance affecting the neurobiochemical sleep regulation. These studies were based on CSF metabolite levels and provided evidence for a high serotonin metabolite (5HIAA) level. It is tempting to hypothesize that the biochemical disturbance has led to encroachment of non-REM sleep patterns on both wakefulness and REM sleep. Further discussion deals with the bilateral-synchronous spike activity and its relationship to arousal patterns in sleep.
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The analgesic effect of etorphine was compared with that of morphine in rats with electrolytic lesions of the nucleus medianus raphe or injected intraventricularly with 6-hydroxydopamine. The effect of both compounds was markedly reduced in animals with raphe lesions, but not significantly modified in those receiving 6-hydroxydopamine. Etorphine and morphine significantly increased the forebrain levels of 5-hydroxyindolacetic acid when administered subcutaneously at doses of 5mg/kg and 2 microgram/kg, respectively. Neither drug significantly affected the forebrain levels of monoamines. It is concluded that, as for morphine the integrity of the serotoninergic system in the brain is important for the full analgesic effect of etorphine.
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Six neurotoxins were purified from Dendroaspis viridis venom using gel filtration and equilibrium chromatography. The amino acid sequences of two of these neurotoxins (72 and 73 residues, five disulphide bridges) have been determined using almost exclusively automated Edman degradation. These two sequences are very similar: the only differences lies in the presence of one extra glycine at the C-terminal end of one of them. There is a good homology with the sequences of toxins now isolated from other Elapidae and Hydrophidae venoms.
The plasma concentration of dopa was studied in 15 parkinsonian patients after a single administration of L-dopa. The study was undertaken in order to determine if correlation between plasma dopa concentration and clinical performance as a result of the tests carried out before and after a single dose of dopa, was present. Our data confirm the absolute absence of correlation between dopa levels in plasma and clinical improvement during long-term treatment. Moreover, clinical responses to the performance tests were not related to the concentration of circulating L-dopa in the plasma. Therefore dopa levels cannot be useful in clinical practice but only for the prevention of too high concentrations of plasma L-dopa which often cause a few side-effects.
The complete amino acid sequence of toxin III of Naja haje (72 residues) has been established mainly by use of a protein sequenator (identification of 70 residues). The two C-terminal residues have been determined by digestion with carboxypeptidases A and B. Addition of succinylated protein or peptide greatly improved the performance of the sequenator for the Edman degradation of peptides: on one peptide (39 residues) degradation went to step 34 with a protein program and on two peptides (10 and 13 residues) degradation reached the last amino acid with a peptide program (use of dimethylbenzylamine). Amino acid analysis of tryptic peptides obtained by digestion of the C-terminal cyanogen bromide peptide are in full agreement with the sequence established by automatic degradation. The sequence of toxin III of Naja haje is unique and is very similar to that of Naja nivea alpha (although there are 9 differences), of Naja melanoleuca b (11 differences) and also to that of Naja naja A (18 differences).
The apamin sequence has been synthesized by the solid-phase procedure. The synthetic peptide showed the same physiochemical and chemical properties as natural apamin in the following tests: paper electrophoresis, amino acid analyses after acid and enzymatic hydrolyses, sequence analysis, electrophoreses after tryptic and chymotryptic digestions. Synthetic apamin was as active as natural apamin in the neurotoxic assay in mice (LD50, after subcutaneous injection, for the 20-g mouse: 58 mug).
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