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Biomedical subjects

E Silva

Publications and source records attributed to E Silva.

At least 127 records · Page 7Linked to original sources

Uterine papillary serous carcinoma (UPSC) treated with cisplatin, doxorubicin, and cyclophosphamide (PAC).

Uterine papillary serous carcinoma (UPSC) is an aggressive malignancy that accounts for a disproportionate number of intraabdominal failures among endometrial carcinoma patients. The histologic appearance and tendency toward intraabdominal spread resemble those of papillary serous adenocarcinoma of the ovary. Because approximately 70% of untreated ovarian carcinoma patients respond to platinum-based chemotherapy, it has been suggested that UPSC patients might respond to similar treatment regimens. Twenty patients with UPSC were treated with cisplatin, doxorubicin (Adriamycin), cyclophosphamide (PAC) chemotherapy between January 1982 and December 1989. They included 9 patients with advanced primary disease, 5 with recurrence, and 6 who received PAC as adjuvant therapy. Patients received a mean of five cycles of PAC. Only 2 of 11 patients with measurable disease greater than 2 cm achieved complete clinical responses of 12 and 31 months duration; there were no partial responses. Actuarial 5-year survival for all patients was 23%. The mean progression-free interval was 9 months. Patients with clinical stages I or II disease had a higher survival rate than those with stage III or IV disease (P = 0.003). Survival did not correlate with depth of myometrial invasion (P = 0.81) or size of residual tumor following initial surgery (P = 0.16). Estrogen or progesterone receptors were detected in 10 of 11 tumors tested. Seven of 9 patients tested had elevated serum levels of CA-125 (greater than 35 U/ml). Correlation between CA-125 value and clinical course was demonstrated in 3 of 5 patients who had serial measurements. Of all patients, 3 are currently alive; 1 has documented disease. Moderate to severe toxicity was seen in 14 patients (70%). There was one possible treatment-related death from cardiomyopathy. UPSC, despite its histologic and clinical similarities to ovarian carcinoma, was relatively resistant to PAC chemotherapy in this mixed group of patients.

Adult↗

Clinical features and treatment of Elapidae bites: report of three cases.

This report describes two accidents, involving snakes of the Micrurus corallinus species, where compromising respiratory function was not observed and the specific anti-elapidic serum was the single therapy used, and a third incident, probably involving Micrurus frontalis, where neostigmine was used to remedy respiratory failure.

Adult↗

Competitive parabolic inhibition of bovine trypsin by bis-benzamidines.

1. Competitive parabolic inhibition, a rare type of inhibition of one-substrate enzymes, is described for alpha- and beta-trypsin. The enzymes were so inhibited by two bis-benzamidines, 4-4'-diazoamino-bis-benzamidine, Berenil (DABB) and its platinum complex, DABB-PtCl2, acting on acyl-amino acid and -peptidyl nitroanilides (Nan) substrates, when inhibitor concentrations exceed 10 mM and approach the millimolar range. 2. The type of nonlinear inhibition observed requires ternary complex formation between one enzyme molecule and two inhibitor molecules (M.E.M), and also permits the formation of the mixed ternary complex (M.E.S). Binding of the first DABB molecule to the active center of trypsin takes place with Ki values of ca. 1.50 microM for both alpha- and beta-trypsin. The secondary binding site binds the inhibitor with dissociation constants Ki2 close to 0.25 mM for both forms of the enzyme, as determined with different substrates. 3. The dissociation constants of the ternary mixed complexes (Ksi and Kis), however, depend on the structural features of the substrates, which are of negligible importance for Bz-Arg-Nan, but significant for Ac-Phe-Arg-Nan and D-Val-Leu-Arg-Nan, reflecting subsite interactions between S1-S3 and S'2. 4. Pentamidine, a diamidino-4,4'-diphenoxy-alkane with a flexible chain, behaved as a strict competitive inhibitor. This implies that the triazene moiety of DABB is involved in the interaction between the inhibitor and the secondary binding site of the enzyme.

Animals↗

A light-induced tryptophan-riboflavin binding: biological implications.

We review here the covalent photo-binding induced by visible light between the essential amino acid tryptophan and the vitamin riboflavin. We discuss the biological implications of this photoadduct in relation to the hepatotoxic and cytotoxic effect associated to parenteral nutrients and to culture media exposed to the action of light, respectively. We also analyze the formation of a photo-binding between riboflavin and the residues of tryptophan present in the proteins of the eye lens, a tissue which is permanently exposed to visible light.

Animals↗

Photo-induced riboflavin binding to the tryptophan residues of bovine and human serum albumins.

The photobinding between riboflavin and the Trp residues from human and bovine serum albumins at two pH-dependent protein conformations was studied. At pH 7.0 both proteins showed photo-adduct formation with hyperbolic kinetics. In the bovine serum albumin this is attributed to the different locations of the two Trp residues. In the case of the human serum albumin, which has only one Trp residue, this behaviour may be related to different molecular conformations of the protein, as is also manifest in the iodide quenching experiments. At pH 3.5, the kinetics of the photo-adduct formation were found to be slower and showed a monophasic behaviour. These results are due to the conformational change of these proteins at acidic pH; the Trp residues of both proteins being now located in a more hydrophobic environment. When bovine serum albumin was anaerobically irradiated at pH 7.0 in the presence of 14C-riboflavin and then cleaved by CNBr, two peptides were obtained, containing the Trp-134 and Trp-212 residues, respectively. The incorporation of 14C-riboflavin in these samples was significantly higher at the level of the peptide containing the Trp-134 residue. Furthermore, it was demonstrated, that the energy transfer from enzymatically generated triplet acetone to riboflavin can also promote the binding of this vitamin to the Trp residues of human and bovine serum albumins.

Animals↗

Prognostic indicators for invasive carcinoma of the vulva.

Three hundred sixty-five patients with invasive squamous cell carcinoma of the vulva have been treated at M.D. Anderson Cancer Center between 1944 and 1990. We undertook a rigorous review of the medical records, and a Cox proportional hazards model was applied to examine predictors of both failure to survive and recurrence. Significant predictors of both failure to survive and recurrence included tumor size, clinical stage, therapy aim, pelvic or inguinal nodal metastases, and positive margins. We then undertook an analysis of Stage I and II lesions treated with a curative aim to see if there was a difference in survival or in disease-free interval between those patients treated with radical vulvectomy and those treated with radical wide local excision. There was no survival advantage from the radical vulvectomy procedure. We conclude that careful selection may allow us to choose some patients for less radical procedures.

Carcinoma↗

Effects of pH and ionic micelles on the riboflavin-sensitized photoprocesses of tryptophan in aqueous solution.

The effects of pH and ionic micelles on the rates of product formation following irradiation of riboflavin in the presence of tryptophan were investigated by absorption and fluorescence spectroscopy. Under anaerobic conditions, formation of riboflavin-tryptophan adducts was inhibited in acid solutions and by the addition of anionic (sodium dodecylsulphate) and cationic (cetyltrimethylammonium bromide) micelles. The oxidation of tryptophan photoinduced by riboflavin was considerable faster in basic solutions.

Cetrimonium↗

Fatty infiltration of the liver: quantification with phase-contrast MR imaging at 1.5 T vs biopsy.

Quantification of hepatic fat content by application of MR phase-contrast imaging (Dixon method) at 1.5 T was compared with results of biopsy in 16 patients with a variety of liver abnormalities. Motion artifact was suppressed by employing six or eight averages of short TR in-phase (echo offset, 0 msec), out-of-phase (echo offset, 1.1 msec), and in-phase (echo offset, 2.2 msec) spin-echo pulse sequences. The 360 degree out-of-phase sequence was used to assess the impact of T2* decay on this method of estimating fat fraction. A standard two-echo long TR sequence also was obtained in all patients. Histologic preparations from the biopsy specimens were examined by a pathologist who had no knowledge of the MR results and were graded according to overall visual assessment as belonging to one of four categories of fat fraction. Results of the MR-calculated apparent fat fraction were compared directly with biopsy category and were also placed in MR fat fraction categories, allowing estimation of the statistical correlation between the biopsy and MR grading systems. Eight of eight patients with biopsy categories indicating a fat fraction of less than 0.25 were computed by MR to have a fat fraction of less than 0.1. Seven of eight patients with biopsy categories indicating a fat fraction of greater than 0.25 were computed by MR to have a fat fraction of at least 0.24. The MR-calculated apparent fat fraction category correlated significantly with the histologic biopsy category (r = .86, p less than .01). When compared with the in-phase image, decreased signal from liver was visually apparent on the 180 degree out-of-phase images in all cases in which the fat fraction was at least 0.24, but there was no indication of fatty liver on the standard T1- or T2-weighted images. Calculated T2 also showed no correlation with degree of fatty deposition. Correction for T2* decay by using the 360 degree out-of-phase acquisition in addition to the standard 0 degree and 180 degree out-of-phase images had little effect on fat fraction computation. Phase-contrast MR is a promising noninvasive method for quantitative assessment of fatty deposition in the liver.

Adult↗

Enzymatic generation of triplet acetone by deglycosylated horseradish peroxidase.

A study of the effects of deglycosylation of horseradish peroxidase on protein conformation, as well as on its catalytic activity of oxidation of isobutyraldehyde or its enol form to triplet acetone and formic acid, was performed. The loss of carbohydrates leads to structural modifications of this enzyme. This is confirmed by a change in the circular dichroism spectrum, an increase in tryptophan's environment polarity, and a loss of the chiral specificity toward D- and L-tryptophan. Deglycosylation does not destroy either the peptide backbone or the amino acid residues and does not affect the heme group content of the protein. The rates of oxygen uptake and light emission observed when horseradish peroxidase oxidizes isobutyraldehyde or the trimethylsilyl enol ether form of the latter are reduced when the enzyme is 70% deglycosylated. Concomitantly, the acting deglycosylated enzyme becomes inactivated during the course of the reaction. It appears that the carbohydrate moiety plays an important role in the protection of the peroxidase from damaging effects induced by triplet acetone and in the stabilization of the three-dimensional structure of this enzyme.

1-Propanol↗

Calcium oxalate crystals in breast biopsies. The missing microcalcifications.

Most calcifications detected by mammography and specimen radiography are readily identified by histologic sections stained with hematoxylin and eosin (H&E) or the von Kossa stain. However, calcifications composed of calcium oxalate crystals are not always seen in sections stained with H&E or with von Kossa. To study the incidence of calcium oxalate crystals in breast biopsies, we used polarized light microscopy to review 153 needle-localization breast biopsies. Birefringent crystals were observed in 19 cases (17 benign and 2 malignant), but typical calcium phosphate microcalcifications were revealed by H&E in only 16 of these 19 cases. Multiple H&E sections through the blocks of the remaining three cases did not reveal typical microcalcifications. These crystals did stain with silver nitrate/rubeanic acid with 5% acetic acid pretreatment but failed to stain with von Kossa and alizarin red at pH 4.2. This suggested that they were composed of calcium oxalate. Analytical electron microscopy performed in one of the three cases without typical microcalcifications demonstrated only a calcium peak of energy-dispersive x-ray analysis and an electron-diffraction pattern compatible with calcium oxalate monohydrate. We conclude that discrepancies between the amount of microcalcifications seen on the mammogram or on the x-ray film of the specimen or the paraffin blocks and the amount of microcalcifications seen on the H&E slides may be explained by the presence of calcium oxalate crystals. These crystals are detected with specimen radiography but are not easily seen on H&E slides unless polarized light microscopy is used. Polarized light microscopy and silver nitrate/rubeanic acid with 5% acetic acid pretreatment should be used for breast biopsy specimens when typical microcalcifications are not seen on H&E-stained sections.

Biopsy, Needle↗

[Blood sugar response to administration of bran or guar added to pasta in children with type I diabetes].

Blood sugar profiles after administration of pasta with (PG) and without (P) guar have been evaluated in 30 young type I diabetic children. Maximum increase of blood sugar was observed at 30' (mean = 21 mg/dl) after P and at 90' (mean = 6 mg/dl) after PG. Maximum decrease in blood sugar levels was reached at 180' in both groups (50 mg/dl after P and 25 mg/dl after PG). Blood sugar level was significantly different only at 180'. No significant difference was observed analyzing rates of increase.

Blood Glucose↗

A plausible identification of the secondary binding site in trypsin and trypsinogen.

1. The determination of the binding of 4,4'-diazoamino-bis-benzamidine (DABB) to alpha-trypsin by equilibrium measurements in columns indicated a stoichiometry of 2 mol ligand/mol enzyme. One molecule of ligand is bound to the active center, as shown by competitive experiments and Ki. The second molecule binds to the secondary binding site, with Ki2 = 0.63 mM at pH 8.0, 25 degrees C. 2. Bovine pancreatic trypsin inhibitor (BPTI) prevented binding of DABB to both sites, indicating that they are topographically close and within the interface of the trypsin-BPTI complex. 3. On the basis of data from the literature regarding the tertiary structure of the trypsin-BPTI complex, we concluded that the secondary binding site of trypsin is plausibly identified as the same site in trypsin that binds the Arg-17 residue of BPTI, i.e., Tyr-39 and Tyr-151 in bovine trypsin. This site would then correspond to subsite S'2 on the enzyme surface.

Benzamidines↗

Goldthioglucose causes brain norepinephrine and serotonin depletion correlated with increased body weight.

Goldthioglucose (GTG) injected i.p. in mice is known to cause hyperphagia and obesity which is related to ventromedial hypothalamic damage and norepinephrine (NE) depletion in females. In the present experiment 6 doses of GTG were tested in males. After 160 days the monoamine content of whole brain was measured. Norepinephrine (NE) and serotonin (SER) were depleted without changes in dopamine content. Brain NE and SER were both negatively correlated with body weight. These experiments extend earlier studies by suggesting that GTG obesity in mice may be caused by NE depletion in males as well as females and by suggesting that the obesity is also a function of serotonin depletion.

Animals↗

Postexercise electrocardiographic and clinical changes in patients with sick sinus syndrome.

Forty patients with sick sinus syndrome, 15 women and 25 men with a mean age of 53.83 +/- 13.34 years, were studied using a maximal graded bicycle stress test. None of the patients were using a pacemaker or being treated with drugs that would interfere with the sinus node function; one patient had family myocardiopathy and eight suffered from essential hypertension. All patients, including those suffering from very marked bradycardia (less than 40 beats/min) responded to the increased effort with increased heart rate. The exercise test was stopped in 22 patients (55%) after the appearance of clinical signs and in 4 (10%) after ST-segment depression greater than 1 mm. Eight (20%) finished the stress test after reaching the maximal heart rate according to age, due to an increase in sinus rate. The exercise produced or increased extrasystoles in five patients (12.5%), but only one was forced to suspend the test. The Q-T interval, corrected for heart rate according to Bazett's formula (QTc), was measured on the resting ECG before the start of the test and on the ECG recorded immediately following the end of the exercise in all patients, except one with atrial fibrillation. In 24 patients (60%), a QTc mean increase of 0.040 +/- 0.022 sec was observed at the end of the stress test. Fourteen (35%) had the usual shortening due to the increase in heart rate. One patient showed no variation of the QTc. A lengthening of the QTc at the end of the exercise in more than half of the patients was the most intriguing electrocardiographic change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗