Familial defective apolipoprotein B-100: mild hypercholesterolaemia without atherosclerosis in a homozygous patient.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to W Gross.
Explore the source record for details and available documents.
Cytosolic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) synthase (E.C. 4.1.3.5) is a highly regulated enzyme involved in isoprenoid biosynthesis and therefore a potential target for cholesterol-lowering drugs. Up to now, primary structure data have only been available for chicken, rat and hamster HMG-CoA synthase. Using in vitro amplification and direct sequencing, we have determined the nucleotide sequence of the coding region of the human cytosolic 3-hydroxy-3-methylglutaryl CoA synthase cDNA.
Plasma membranes were isolated from carrot (Daucus carota L.) cells grown in suspension culture and treated with phospholipase A2 from snake or bee venom for 10 min. As a result of this treatment, phosphatidylinositol kinase activity was recovered in the soluble fraction. There was no detectable diacylglycerol kinase or phosphatidylinositol monophosphate kinase activity released from the membranes after the phospholipase A2 treatment. Treating the plasma membranes with phospholipase C or D did not release PI kinase activity. The phospholipase A2-released PI kinase was activated over 2-fold by a heat stable, soluble 70 kDa protein. The partially purified 70 kDa activator increases the Vmax but does not affect the Km of the phospholipase A2-released PI kinase.
A two-step polymerase chain reaction (PCR) method for the rapid detection of the apolipoprotein B(Arg3500----Gln) mutation in a mixture of pooled blood samples is described. In the first step PCR, a short gene fragment surrounding codon 3500 is amplified. Subsequently the reaction product is subjected to a second amplification in which a mutation-specific primer is used. A PCR product is generated only if the mutant sequence is present in the DNA pool. Individuals carrying the mutation can then be identified by PCR with mutagenic primers and MspI restriction typing, essentially as described by Hansen et al. (J. Lipid Res. 1991. 32: 1229-1233).
An exploratory needs assessment was conducted among 50 clients of an abstinence-oriented outpatient clinic for adults experiencing coexisting drug abuse and chronic mental disorders. Findings revealed that, despite education and prevention efforts, sample members possessed considerable misinformation about AIDS and continued to engage in high risk heterosexual practices. Their knowledge level was not associated significantly with their admission diagnoses. Knowledge level also did not correlate significantly with safer sexual practices. These findings have implications for the development of AIDS education and prevention programs for dually disordered clients. To be effective, AIDS prevention and education efforts must be targeted at the clients' specific needs. Clear, explicit information about AIDS must be provided. In addition, behavioral-attitudinal change strategies that focus on the high-risk situations encountered by the clients and teach them alternative safer sex practices are required.
sn-1 Palmitoyl lysophosphatidylinositol is found in carrot suspension culture cells and can be phosphorylated to [32P]lysophosphatidylinositol monophosphate (LPIP) when [gamma 32P]ATP is added to isolated membranes. Based on in vivo labeling studies, [3H]inositol sn-1 palmitoyl LPIP was found predominantly in the plasma membrane-rich fraction or upper phase isolated by aqueous two-phase partitioning and LPI was found in the intracellular membrane-rich fraction or lower phase (Wheeler and Boss, Plant Physiol. 85, 389-392, 1987). While both membrane fractions phosphorylated LPI in vitro, the apparent Km for LPI in the intracellular membrane fraction was 180 microM and for the plasma membrane was 580 microM. When cells were treated with the ionophore, monensin, the percentage of [3H]inositol LPIP increased in the whole cell lipid extract. However, the monensin treatment decreased the amount of [3H]inositol LPIP and PIP recovered in the plasma membrane fraction relative to the sum of the individual lipid, [3H]inositol LPIP or PIP, respectively, recovered in both membrane fractions.
An immunoblotting method for the determination of apolipoprotein E (apoE) phenotypes has been developed. Delipidated plasma proteins are focused in an immobilized pH gradient, and transferred to polyvinylidene difluoride (PVDF) membranes. ApoE isomorphs are identified by immunoperoxidase staining. The method allows reproducible assignment of apoE phenotypes without isolation of triglyceride-rich lipoproteins. Only small amounts of serum are required. There are several important steps in the procedure: (i) delipidation is indispensable, (ii) carrier ampholytes have to be added to the gels and to the sample buffer, and, (iii) on immunostaining, polyvinylidene difluoride membranes provide an excellent signal-to-background ratio.
The protein moiety of lipoprotein (a) consists of apoB-100 and apolipoprotein (a). Lipoprotein (a) is an independent risk factor for premature atherosclerosis. Apolipoprotein (a) and plasminogen are structurally homologous. Through interference with the fibrinolytic system, lipoprotein (a) may act as a thrombogenic factor. Therefore, we have determined apolipoprotein (a) in 203 patients with venous thrombosis and/or embolism below the age of 45 years and in 115 healthy volunteers. The frequency distribution of apolipoprotein (a) in thrombosis patients resembled that in the reference group. It is concluded that there is no clinically relevant association between apolipoprotein (a) concentrations and the risk of venous thrombosis in young subjects.
The open-ended study of the International Working Group on Mycobacterial Taxonomy is an ongoing project to characterize slowly growing strains of mycobacteria that do not belong to well-established or thoroughly characterized species. In this fourth report we describe two numerical taxonomic clusters that represent subspecies or biovars of Mycobacterium simiae, one cluster that encompasses the erstwhile type strain of the presently invalid species "Mycobacterium paraffinicum," one cluster that is phenotypically very similar to Mycobacterium avium and Mycobacterium intracellulare but may be a separate genospecies, one cluster that appears to be phenotypically distinct from M. avium but reacts with a nucleic acid probe specific for M. avium, and three tentatively defined clusters in proximity to a cluster that encompasses the type strain of Mycobacterium malmoense. Of special practical interest is the fact that one of the latter three clusters is composed of clinically significant scotochromogenic bacteria that can be misidentified as the nonpathogenic organism Mycobacterium gordonae if insufficient biochemical tests are performed.
Explore the source record for details and available documents.
Existing models describing the kinetics of receptor-effector interaction were found to be insufficient to account for the experimental findings on adenylate cyclase activation by A2 adenosine receptors described in the preceding manuscript [Mol. Pharmacol. 39: 517-523 (1991)]. We have, therefore, chosen another approach and have developed discrete computer simulations of receptor-effector interactions taking place on a spherical membrane. These simulations were based on the following principles: (a) receptors activate effectors in a catalytic manner, and (b) diffusion of receptors and effectors is slow, so that receptors will only activate effectors that are in their vicinity at the time of agonist occupation. Using several experimentally determined parameters, these simulations could reproduce the experimental findings on adenylate cyclase activation by A2 adenosine receptors described in the preceding manuscript. In addition, by appropriate choice of the simulation parameters, they are shown to accommodate the behavior of several other models of receptor-effector interactions.
Under standardized conditions, 26 pregnant women with pregnancy-related hypertension of different degrees were submitted to cardiogram-synchronous recording of fetal body and respiratory movements. The gestational age was between the completed 34th and 38th weeks. Of the 26 fetuses of the risk group, 20 were normotrophic and 6 hypotrophic. 40 normotrophic unimpaired fetuses of the same gestational age served as a control group. The average duration of the examination period was 70 minutes. The fetal movement and acceleration behaviours did not differ between the normotrophic fetuses of the risk group and those of the control group. The hypotrophic fetuses from the risk group, however, had significantly lower fetal body and respiratory activities than the normotrophic fetuses from this group. The same holds true for the degrees of heart rate activity. It can be concluded that pregnancy-related hypertension as the only pregnancy complication does not have a measurable influence on fetal movement and acceleration behaviours. This is true for both treated and untreated pregnancy-related hypertensions. The severity of pregnancy-related hypertension is not primarily reflected in changes of fetal movement and acceleration behaviours, either. This means that the parameters presented are not suited to prognosticate the effects of pregnancy-related hypertension on the fetus a priori. The situation becomes quite different if in addition to pregnancy-related hypertension some intrauterine fetal growth retardation develops. In this case, the fetus indicates its impairment by increasingly impaired movement and heart rate activities as a consequence of chronic oxygen deficiency.
Clotting analysis in 30 patients with bleeding complications in malignant hematological diseases revealed the following troubles: The global tests, Quick's index and partial thromboplastin time markedly differed from normal. Activity of clotting factors revealed hypo- or hyperfibrinogenemia, disturbances of the prothrombin complex (factors II, VII, IX and X), decrease of factors V, VIII, XII. Factor XI (= PTA) was not diminished in any case. Regarding the fibrin-stabilizing factor (factor XIII), its activity was significantly decreased in 30 patients with solid tumors and in 30 patients with hemoblastoses. Faulty clotting balance was characterized by hyperfibrinolysis or disseminated intravascular coagulation (DIC) accompanied by reactive hyperfibrinolysis. About one quarter of the patients with malignant disturbances of the hematopoetic system demonstrated (mostly amegacaryocyte) thrombocytopenia. Finally, treatment of bleeding complications in malignant neoplastic diseases is pointed out.
Explore the source record for details and available documents.
In ten healthy volunteers infusion of 7 micrograms/kg orciprenaline produced typical changes in carbohydrate and fat metabolism due to beta-adrenergic stimulation. Pretreatment with intravenously administered propranolol or metoprolol significantly inhibited orciprenaline-induced changes in systolic blood pressure, heart rate and plasma FFA, potassium, glucose and glycerol levels. Propranolol (0.1 mg/kg) seemed to be more effective than metoprolol (0.2 mg/kg) even in inhibiting predominantly beta 1-adrenergic responses.
Explore the source record for details and available documents.
Kallikrein given in a dose of 3 times 200 KE daily over 7 days caused under our test conditions an increase of ATP in blood and a decrease of lactate and especially of pyruvate. Glucose showed under this condition a higher utilization with a lowering of glucose in blood and an increase of the RQ. The acid-base metabolism follows these tendencies. In other experiments we did not find such effects, so the results must be specific to kallikrein.
The therapeutic value of non-steroid anti-inflammatory agents for therapy of rheumatoid arthritis is discussed and a long-term study is described which was carried out for up to 12 monts on tolerance of ketoprofen compared with indomethacin. Objective laboratory data were used as criteria for possible influence on organ function. No abnormalities in renal and liver function were observed.