Biomedical subjects
Publications and source records attributed to G Brulé.
Ethers and thioethers of monosaccharides have been synthesised which show potent toxicity to mouse (LD50 > or = 4 g.kg-1 O.W. and 0.2 to 1.5 g.kg-1 I.P.W.). A study of calcium antagonist activity for the full series of compounds indicated that the activity was similar for both O- and S- ethers and maximum activities were observed for monoacetoneglucose ethers possessing carbon chain close to 8 carbons.
An improved procedure is described involving gel permeation and anion-exchange chromatography for the purification of four major hen egg white proteins. The procedure involves a first-step purification of ovomucin and lysozyme by gel permeation on a Superose 6 Prep Grade column. In the second step, anion-exchange chromatography on Q Sepharose Fast Flow led to the isolation of ovotransferrin and ovalbumin from a gel permeation chromatographic peak. The purities were estimated as ca. 80, 100, 80 and 100% for ovomucin, lysozyme, ovotransferrin and ovalbumin, respectively. The purification yield was over 60% for each protein. Further characterization of purified lysozyme revealed that it was fully active and homogeneous in relation to the electrospray ionization mass spectrum. The electrospray ionization mass spectrum showed different ovotransferrin species. The amino acid composition of purified ovomucin was compared to those published previously.
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ATP hydrolysis-pCa and isometric tension-pCa relationships were determined for isolated myofibrils under a variety of ionic conditions i.e. in presence of Cl- ions (normal conditions), in presence of CH3COO- or CH3OSO3- (ions replacing all or a part of Cl- ions). In all ionic conditions, these relationships have a S-shape. For each ionic condition, the relationships between isometric tension or ATP hydrolysis and pCa were parallel, but the isometric tension-pCa was shifted towards a smaller value of pCa. The relation between ATP hydrolysis and pCa has been analysed by means of the enzymatic reaction described by Michaelis-Menten. The analysis of isometric tension-pCa relationship can be also described by using the consecutive scheme of reaction for the co-operative action of two Ca2+ ions in the process of tension activation given by Ashley & Moisescu (1977) for barnacle myofibrils. The dissociation constant (k1) equal to the one that we determined for the ATP hydrolysis probably corresponds to the Ca2+ binding site of troponin (M1). This association (M1-Ca) would lead to the phosphorylation of the second site (M2) localized on myosin, which can bind a Ca2+ ion. In presence of CH3COO-, ATP hydrolysis (V) was increased with no change of the affinity of the first site for the Ca2+ ion. At the opposite, V did not change but the affinity of M1 site was decreased in presence of CH3OSO3-. CH3OSO3- must be considered as a competitive inhibitor whereas CH3COO- must be considered as an activator ion of the ATP hydrolysis reaction. In all cases, the relationship between isometric tension and ATP hydrolysis was hyperbolic.
18 relapses of non seminomatous germ cell cancer of the testis are studied, among a group of 112 patients treated from 1974 to 1978, of which 90 are in complete remission. The study of these cases shows the bad prognosis value of yolk sac tumor component at histological examination. Relapses are more frequent in the stages with lymph node involvement treated by retroperitoneal lymphadenectomy followed by chemotherapy without cis-platinum. Cis-platinum chemotherapy decreases relapse rate in theses stages and increases complete remission rate in metastatic stages.
In this study, we used fasted, preruminant calves fitted with a double proximal cannula in the duodenum; gastric evacuation was investigated by recovering products leaving the abomasum after a test meal. Five types of meal were given: whole milk, skimmed milk, casein solution in water, casein solution in a mineral medium simulating the permeate of highly-filtered milk, and whey. Gastric emptying of nitrogen was relatively slow. The coagulation of "milk diets" slowed down this emptying. Precipitation of "casein diets" at acid pH also slowed down emptying, but to a lesser degree. The "casein diets", more proteolyzed than the "milk diets", released larger amounts of non-protein nitrogen (NPN) into the intestine. Calcium emptying was highly related to NPN emptying, demonstrating the important role of acid peptides (phosphopeptides) from casein hydrolysis.
Among 112 cases of non-seminomatous testicular tumours treated from 1974 to 1978, there were 13 thoracotomies for the excision of thoracic lesions: in 4 cases for recurrence, in 9 for incomplete remission. In 8 cases, one of the 4 recurrences and 7 of the 9 Stages III, a cure was obtained. In all cases thoracic surgery was combined with chemotherapy including bleomycin and cis platinum and in some cases lombo-aortic lymph node dissection. The hope of cure at metastatic stages of non-seminomatous testicular tumours is 50%.
Cerebral metastases occur in 6% of cases of testicular cancer. In our study of 5 cases they occurred during the course of the disease (with a delay of 4-18 months, at the same time as pulmonary and abdominal metastases). The prognosis in these cases is poor (presence of choriocarcinomatous or vitelline elements, advanced stages). The diagnosis is easily established (clinical, encephalogram, scanner); the prognosis is hopeless (5 deaths in 3-90 days). When a metastasis is the first diagnostic clue (one case), the prognosis is slightly better (9 month survival). The incidence of cerebral metastasis is the same now as it was before the introduction of effective chemotherapy in patients who die from testicular cancer, but the death rate from this malignancy has decreased since the introduction of active chemotherapy with cisplatin. Hence, there is no indication for prophylactic treatment for cerebral metastases in patients in remission since metastases only appear in cases which are resistant to treatment.
A phase II trial was conducted in 57 patients with advanced metastatic breast cancer given 2-N-methyl 9-hydroxy-ellipticine (NMHE) as 100 mg/m2 weekly. Evaluation of response, after at least 4 injections, was possible in 46 patients. Two complete regressions (of 3 and 12 months) and 7 regressions of over 50 p. cent were observed, a total regression rate of 19 p. cent. Regression was mainly observed in cutaneous or subcutaneous metastases. No objective regression was noted for pulmonary or hepatic metastases. Bone metastases were not taken in account when assessing response to treatment. Absence of haematological changes must be emphasized. The most frequent side effects were anorexia, nausea +/- vomiting and dryness of mouth. Major toxicity was intravascular haemolysis, observed in 6 of 175 patients receiving NMHE in the Institut Gustave-Roussy, always controlled by symptomatic treatment. This product, of acceptable efficacy in breast cancer treatment, will probably occupy an original place in anti-cancer chemotherapy because of its lack of myelotoxicity.
One hundred and one patients with terminal cancer suffering severe pains reluctant to other treatment have received morphine by mouth, in a regular regimen. The doses range between 5 and 60 mg every 4 hours. 71 p. cent of our patients have their pain alleviated without any side effect impeding the treatment.
We have conducted a phase II trial of cisplatinumdiamminodichloride (CPDD) which not only demonstrated its remarkable activity in embryonic carcinoma of the testes, but also in ovarian carcinoma, in melanoma, and in epidermoid carcinoma, especially of the head and of the uterus cervix. Its toxicity, manifested mainly in the digestive and renal tracts, confines its administration to hospitalized patients only. This compound is now indicated in combination therapy for the above-mentioned tumors.
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Fifty one patients with terminal cancer suffering severe pains reluctant to other treatment have received morphine by mouth, in a regular regimen. The doses range between 5 and 50 mg every 4 hours. 60% of our patients have their pain alleviated without any side effect impeding the treatment.
We have conducted a phase II trial of cisdiammino-dichloro platinum (CDDP) which demonstrates its remarkable activity in testis embryonic carcinoma, in ovary carcinoma and in epidermoid cancers, especially head and neck and uterus cervix carcinoma. Its toxicity in mainly digestive and renal. This compound is now indicated in combinations in the case of the above mentioned tumors.
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Experiments were performed to investigate the modifications of electrical activity and the loss of contraction by examination of the ultrastructure. These alterations were obtained with a control physiological solution (artificial sea water, ASW) which was made hypertonic by adding sucrose, glycerol, choline chloride or urea. 1. Under these conditions, the ultrastructural results show that: a) all those substances induce a modification of the coupling junction (either diad or triad). This modification can explain the inhibition of the mechanical phenomenon; b) sucrose (Figs. 6C and 6D) and glycerol (Figs. 4A and 4B) induce alterations of the surface membrane and of the tubular system (less important with glycerol). They can explain the decrease of the resting potential and the abolishment or the modification of the action potential; c) in contrast, choline chloride (Figs. 7A to 7E) and urea (Figs. 9A to 9F) only modify the organisation of the coupling junction. The action potential is maintained. 2. A short exposure of the fibre in an isotonic sucrose solution (Figs. 5A to 5D) deeply modifies the tubular system, particularly, in cutting it off from the sarcolemma. 3. Choline chloride and urea produce similar changes in the ultrastructure but as urea is not ionized, it can be added to the ASW to investigate the electrical phenomenon which cannot be modified by contraction.
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