Evolution and the senescence process. Broadening our view of aging.
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Aged↗
Biomedical subjects
M Burstein
Publications and source records attributed to M Burstein.
Preferential expression of novel MUC1 tumor antigen isoforms in human epithelial tumors and their tumor-potentiating function.
The human MUC1 gene expresses at least 2 type 1 membrane proteins: MUC1/REP, a polymorphic high m.w. MUC1 glycoprotein often highly expressed in breast cancer tissues and containing a variable number of tandem 20 amino acid repeat units, and the MUC1/Y protein, which lacks this repeat array and, therefore, is not polymorphic. Despite their documented importance in signal transduction processes, the relative expression of the 2 isoforms in epithelial tumors is unknown. Using antibody reagents which recognize different MUC1 domains, the expression of these isoforms in malignant epithelial cells has been evaluated. A comparison of the amounts of the 2 isoforms revealed preferential expression of the novel MUC1/Y protein in breast cancer tissue samples. Furthermore, although the MUC1/REP protein is almost undetectable in HeLa cervical adenocarcinoma epithelial cells, the MUC1/Y isoform is extensively expressed in these cells. The presence of the MUC1/Y sequence as well as that of an additional tandem-repeat-array-lacking isoform, designated MUC1/X, were demonstrated by reverse transcriptase PCR amplification of RNA extracted from HeLa and ovarian carcinoma cells. It has been shown previously that the MUC1 cytoplasmic domain interacts with the SH2 domain containing GRB2 protein, which transduces signals to ras, a protein which in its activated form can lead to cell transformation. We present here data demonstrating that MUC1/Y isoform expression increases the tumorigenic potential of DA3 mouse mammary epithelial cells; in contrast, potentiation of tumorigenicity is not observed with MUC1/REP expression. Our studies thus demonstrate that expression of the MUC1 gene in epithelial tumors can give rise to substantial levels of MUC1 proteins devoid of the tandem repeat array, which are generated by alternative splicing mechanisms.
Amino Acid Sequence↗
Retrieval of occluding unexpanded Palmaz-Schatz stent from a saphenous aorto-coronary vein graft.
The Palmaz-Schatz coronary stent is used frequently to reduce the rate of restenosis of balloon angioplasty in saphenous vein grafts. In many European centers, the stent, manually crimped on a balloon, is advanced across the stenosis without a protective sheath. This report describes a patient in whom an attempt to deploy a stent in the orifice of a saphenous vein graft was complicated by dislodgement of the unexpanded stent from the balloon. The unexpanded stent caused immediate occlusion of the vein graft and severe ischemic symptoms. The stent was retrieved by inflation of another balloon in the graft, distal to the stent, pulling the balloon toward the guiding catheter, and then withdrawing the whole system.
Aged↗
[Jacuzzi-immersion for obstetric analgesia].
The effect of immersion in a jacuzzi in relieving labor pains, and on cervical dilatation was examined in 40 parturients. They were immersed in the jacuzzi during labor for an average of 25.5 minutes. Labor pains decreased during immersion by 2.59 degrees (scale of 0-10) compared with an average increase in labor pains of 0.25 degrees in 40 control women who were not immersed (p < 0.01). The cervical opening increased during immersion by an average of 1.5 cm in the test group, compared with 0.3 cm in the controls (p < 0.01). Immersion in a jacuzzi during labor is apparently associated with analgesia and accelerated cervical dilatation.
Analgesia, Obstetrical↗
Low peptic ulcer and high gastric cancer prevalence in a developing country with a high prevalence of infection by Helicobacter pylori.
We compared the prevalence rates of peptic ulcer (duodenal and gastric) and gastric cancer in 1,796 dyspeptic Peruvian patients with those reported in 2,883 similar patients from developed countries. The prevalence of total peptic ulcer was significantly lower, and that of gastric cancer significantly higher, in the Peruvian patients. The prevalence of gastric ulcer was lower but not significantly so. We deduced that the significantly lower prevalence of total peptic ulcer was directly related to the low prevalence rate of duodenal ulcer. We hypothesize that the reason for these differences was probably a higher prevalence of Helicobacter pylori-associated chronic atrophic gastritis with hypochlorhydria in the Peruvian patients. Hypochlorhydria decreases the predisposition to peptic ulcer (especially duodenal ulcer), and chronic atrophic gastritis may predispose an individual to gastric cancer.
Adult↗
Concentrations of high-density lipoprotein subfraction HDL2 and lipoprotein A-I in a random population of healthy subjects.
High-density lipoproteins (HDL) are now currently subdivided according either to density and size-HDL2 and HDL3--or to surface apoprotein composition--lipoprotein A-I (LpA-I) without A-II, and LpA-I:A-II. In samples from blood bank donors (60 women, 47 men), we evaluated HDL subclasses, LpA-I particles, and other classic risk factors for atherosclerosis and compared them with each other. We found a good correlation between HDL2 and LpA-I (r = 0.74, P less than 0.001), the correlation being more marked in women (r = 0.74) than in men (r = 0.67). LpA-I was also strongly correlated with total apolipoprotein A-I (apoA-I) (r = 0.61), which suggests that LpA-I represents a significant portion of the variable pool of apoA-I. By contrast, LpA-I:A-II but not LpA-I was correlated with HDL3, confirming the preferential association of LpA-I with HDL2. The difference between the sexes was more marked for HDL2 (+66% in women) than for LpA-I (+25%). We conclude that in normolipemic subjects the size of the HDL2 pool depends on that of LpA-I. Considering the speed and low cost of the assay, determination of HDL2 cholesterol might be a useful tool for assessing cardiovascular risk.
Apolipoprotein A-I↗
Cyclic anaphylaxis associated with menstruation.
A middle-aged woman developed recurrent episodes of severe life-threatening anaphylaxis. All episodes were strikingly associated with the first day of menstrual bleeding. Temporary relief was achieved with indomethacin therapy. The patient fully recovered following abdominal hysterectomy and salpingoophorectomy. The possible role of sex hormones and prostaglandin F2 alpha in the pathogenesis of this problem is discussed.
Adult↗
Distribution of HDL2 and HDL3 in a random population of healthy French males and females--evaluation by a two-step precipitation procedure.
A rapid and reliable method for the determination of HDL2 and HDL3 cholesterol is described. The Apo B containing fractions (VLDL, IDL, LDL) were precipitated by addition of dextran sulfate (Mr 500,000) to 2 mmol/l final concentration followed by MgCl2 to a final concentration of 0.05 mol/l. The supernatant, was brought to 6 mmol/l dextran sulfate and 0.250 mol/l MgCl2 to precipitate HDL2. Cholesterol determination on total serum and both supernatants yielded the concentrations of Apo B-associated cholesterol, total HDL, HDL2 and HDL3 cholesterol. The application of this technique to a random population of healthy French people gave HDL-cholesterol values of 1.35 and 1.54 mmol.l-1, respectively, in 93 males and 95 females (p less than 0.001). All of the difference was attributable to HDL2 (0.43 vs 0.65 mmol.l-1, p less than 0.001) while HDL3 were almost identical at 0.92 and 0.91 nmol.l-1. These values are in good agreement with previously reported figures for French individuals, but markedly higher in males than values reported from North America.
Apolipoproteins A↗
Idiopathic sclerosing peritonitis in a man.
Idiopathic sclerosing peritonitis is a rare disease described in young adolescent women, characterized by fibrosis and adhesions of the peritoneum to loops of the small bowel. Here we describe a 35-year-old man who underwent exploratory laparotomy for repeated small bowel obstruction. Only partial resection of the terminal ileum was possible because of adhesions; recurrent abdominal infections and leakage from anastomosis required further resection, which ultimately resulted in short bowel syndrome and malabsorption. The clinical and pathological findings were characteristic for idiopathic sclerosing peritonitis. We review the relevant literature, to confirm, to the best of our knowledge, that this is the first report of a male patient who has developed this rare disease.
Adult↗
Nonthrombocytopenic purpura induced by cefoxitin.
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Aged↗
Rapid method for the isolation of two purified subfractions of high density lipoproteins by differential dextran sulfate-magnesium chloride precipitation.
We describe a rapid and reliable three-step precipitation procedure for the isolation of large amounts of the two major components of high density lipoproteins (HDL) in human serum. Precipitation was accomplished by means of dextran sulfate (DS) of mol. wt. 500,000 and MgCl2. First, all apoB-associated lipoproteins of any density were selectively precipitated with critical concentrations of reagents. Secondly, a subfraction of HDL was differentially precipitated from the apoB-depleted serum by increasing the concentration of both reagents. Eventually, the bulk of the remainder of HDL was precipitated by lowering the pH to 5.4. According to the precipitation patterns and the density profiles, the DS-Mg procedure provides a clear differentiation between the two HDL components. According to the compositional criteria and the ultracentrifugal characteristics, the two polyanion-precipitated subclasses are very similar to, if not identical with, the two density subclasses, the lighter HDL2 and the heavier HDL3, isolated by preparative ultracentrifugation after apoB-containing lipoproteins had been removed.
Chemical Precipitation↗
Toxic epidermal necrolysis associated with acute cholestatic viral hepatitis A.
A 35-year-old man with obvious hepatitis A (HA) developed toxic epidermal necrolysis, which, we suggest, may have been a direct result of the infection with HA virus.
Acute Disease↗
Translocation of cytosolic acetylcholine into synaptic vesicles and demonstration of vesicular release.
The rate of translocation of newly synthesized acetylcholine (ACh) from the presynaptic cytosol of Torpedo electric organ nerve terminals into synaptic vesicles and the extent to which ACh release from these neurons is mediated by a vesicular mechanism were investigated. For this purpose the compound 2(4-phenylpiperidino)cyclohexanol (AH5183), which inhibits the active transport of ACh into isolated cholinergic synaptic vesicles, was employed. Preincubation of purified Torpedo nerve terminals (synaptosomes) with AH5183 does not affect the intraterminal synthesis of [3H]ACh but results in a marked inhibition (85%) of its Ca2+-dependent K+-evoked release. By contrast, the evoked release of the endogenous nonlabeled ACh is not affected by this compound. When AH5183 is added during radiolabeling, it causes a progressively smaller inhibition of [3H]ACh release which is completely abolished if the drug is added after the preparation has been labeled. These findings suggest that most of the newly synthesized synaptosomal [3H]ACh (85%) is released by a vesicular mechanism and that some [3H]ACh (15%) may be released by a different process. The translocation of cytosolic [3H]ACh into the synaptic vesicles was monitored by determining the time course of the loss of susceptibility of [3H]ACh release to AH5183. It was found not to be coupled kinetically to [3H]ACh synthesis and to lag behind it. The nature of the intraterminal processes underlying this lag is discussed.
Acetylcholine↗
Transbronchial biopsies in Wegener's granulomatosis.
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Biopsy↗
Biochemical evidence that acetylcholine release from cholinergic nerve terminals is mostly vesicular.
The nature of the intraterminal compartments from which acetylcholine (ACh) is released following presynaptic stimulation was investigated. This was pursued by examining the effects of the anticholinergic drug 2-(4-phenylpiperidino)cyclohexanol (AH5183) on the release of newly synthesized [3H]ACh and of endogenous ACh from purified cholinergic nerve terminals (synaptosomes) which were isolated from the electric organs of Torpedo. Preincubation of the synaptosomes, with AH5183 (1-10 microM), does not affect either the intraterminal synthesis of [3H]ACh or the uptake of its precursors, but results in a marked inhibition (85%) of the release of the newly synthesized [3H]ACh. However, when AH5183 is added following the accumulation of [3H]ACh in the nerve terminals, it does not affect [3H]ACh release. AH5183 also has no effect on the release of preformed endogenous ACh. These findings, together with the previous in vitro demonstrations that AH5183 is a potent inhibitor of ACh uptake into isolated cholinergic vesicles, suggest that most of the synaptosomal ACh is secreted by a vesicular mechanism.
Acetates↗
Seasonal variations in the muscarinic regulation of acetylcholine release from Torpedo electric organ nerve terminals.
The cholinergic nerve endings of the electric organs of Torpedo ocellata contains presynaptic muscarinic acetylcholine receptors (mAChR) which regulate acetylcholine (ACh) release by negative feedback. The efficiency of this muscarinic regulation varies circannually: maximal inhibition is observed in the winter, much smaller effects in the fall and spring, and no effect is observed during the summer. These variations are accompanied by seasonal changes in the ability of the mAChR to trigger the synthesis of its second messenger (a prostaglandin E-like substance) and in the ability of exogenous prostaglandin E2 to inhibit ACh release. No seasonal changes were found in the number of presynaptic mAChRs. These findings suggest that the observed seasonal variations are due to changes in both the metabolism of prostaglandins in the electric organ and the sensitivity of the ACh-releasing apparatus to the muscarinic second messenger.
Acetylcholine↗
Metabolism of arachidonic acid and prostaglandins in the Torpedo electric organ: modulation by the presynaptic muscarinic acetylcholine receptor.
We have found that Torpedo electric organ readily synthesizes prostaglandin E2 from both exogenous and endogenous arachidonate and that activation of the presynaptic muscarinic acetylcholine receptor increases the rate of prostaglandin E2 synthesis by inducing the release of tissue arachidonate from its phospholipid pools. The incorporation of radiolabeled arachidonate into tissue phospholipids is slow and Ca2+ independent. However, the electric organ slices readily oxidize the externally added, radiolabeled arachidonate via the cyclo-oxygenase pathway, with prostaglandin E2 being the major product (22 +/- 4% of the initial radioactivity). This process is not affected by either Ca2+ or mepacrine. Torpedo electric organ slices also synthesize prostaglandin E2 from endogenous substrates, and release it into the medium. This process, however, is enhanced by Ca2+ and inhibited by mepacrine. Activation of the Torpedo muscarinic acetylcholine receptor by the agonist oxotremorine results in a dose-dependent atropine-sensitive increase in the synthesis of prostaglandin E2 from endogenous tissue substrates and in the concomitant release of arachidonate into the medium. By contrast, oxotremorine has no effect on either the formation of [14C]prostaglandin E2 from exogenous arachidonate, the incorporation of radiolabeled arachidonate into tissue phospholipids or its liberation from prelabeled slices. These results suggest that activation of the muscarinic acetylcholine receptor induces lipolysis which results in the liberation of endogenous arachidonate and its subsequent conversion to prostaglandin E2.
Animals↗