The function of platelets of patients with Alzheimer's disease has been characterized. The shape of platelets is more spherical and the initial rate of platelet aggregation caused by different agonists measured in plasma is faster in the case of Alzheimer's disease and senile dementia of the Alzheimer-type than that of other demented patients: multi infarct dementia and probable vascular dementia. Although fast aggregation is characteristic of activated platelets but the Alzheimer platelets are not hypersensitive. The activation of Alzheimer platelets makes the velocity of ADP induced aggregation slower and it is different than the behaviour of normal activated platelets. The shape-associated parameter and the initial rate of 50 microM ADP-induced aggregation of platelets non-activated and activated by cytochrome C are recommended for establishing the diagnosis of Alzheimer's disease and senile dementia of the Alzheimer-type. The evaluation of these parameters has been discussed. The cytochrome C may be useful to normalize the function of Alzheimer platelets in plasma, not only in vitro.

Journal Article↗

PubMedDate not supplied

Pseudononapeptide bombesin antagonists containing C-terminal Trp or Tpi.

Seven new antagonists of bombesin (Bn)/gastrin-releasing peptide (GRP) containing C-terminal Trp or Tpi (2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-3-carboxylic acid) in a reduced peptide bond were synthesized by solid phase methods and evaluated biologically. The reduced bond in four [Leu13 psi(CH2NH)Trp14]Bn(6-14) analogs was formed by reductive alkylation at the dipeptide stage. In the case of three [Leu13 psi(CH2N)Tpi14]Bn(6-14) analogs, the Trp dipeptide with reduced bond was reacted with formaldehyde to form the corresponding Tpi derivative. These Tpi-containing analogs have a new reduced bond which is structurally more constrained. Leu13 psi(CH2N)Tpi14 analogs inhibit [125I][Tyr4]bombesin binding to Swiss 3T3 cells with IC50 values of 2-4 nM, compared to 5-10 nM for Leu13 psi(CH2NH)Trp14 analogs. Leu13 psi(CH2N)Tpi14 analogs are also more potent than Leu13 psi(CH2NH)Trp14 analogs in growth inhibition studies using Swiss 3T3 cells. The two best bombesin antagonists of this series, [D-Trp6,Leu13 psi(CH2N)Tpi14]Bn(6-14) (RC-3415) and [Tpi6,Leu13 psi(CH2N)Tpi14]Bn(6-14) (RC-3440), inhibited GRP-stimulated growth of Swiss 3T3 cells with IC50 values less than 1 nM. RC-3440 was also active in vivo, suppressing GRP(14-27)-stimulated serum gastrin secretion in rats. Bombesin/GRP antagonists, such as RC-3440, containing the new reduced bond (CH2N) reported herein are very potent.

3T3 Cells↗

PubMedDate not supplied

Changes of salivary amylase in serum and parotid gland during pharmacological and physiological stimulation.

Although serum amylase level is an important diagnostic factor in certain salivary and pancreatic diseases, little information is available regarding the mechanism by which parotid amylase reaches the circulatory system. The present study was carried out to investigate the relationship between parotid isoamylase concentrations in blood serum and in parotid tissue in response to various stimuli. Wistar rats were fed with standard laboratory rodent chow; water was supplied ad libitum. In the first experiment, after a 16-h fasting, rats received either 5 mg/kg pilocarpine or saline (control). In the second study, after fasting, half of the rats were fed for 1 h, the other half received no food. In the third experiment, the changes in serum and tissue enzyme levels were monitored in freely fed animals during the peak-food intake phase, the first 2 h of the dark period. Amylase concentration was determined by using starch as a substrate. Pancreatic and parotid isoamylase levels in serum were separated by gel-electrophoresis utilizing differences in ionic properties of the isoenzymes. As expected, pilocarpine strongly stimulated tissue amylase discharge and serum amylase elevation. Similar, but less pronounced changes were observed not only during refeeding of fasted animals, but also in nonfasted rats during their peak-feeding period. Our data suggest that pharmacological stimulation, such as with pilocarpine or feeding in fasted state, as well as a mild stimulation of parotid function by spontaneous food intake during nonfasted state results in a decrease in parotid tissue amylase activity and a proportional increase in serum levels of parotid isoamylase.

Amylases↗

PubMedDate not supplied

Prevalence of the factor V Leiden mutation in human inflammatory bowel disease with different activity.

BACKGROUND: the developmental mechanism of inflammatory bowel disease (IBD) in patients is unknown, but it may be influenced by different environmental and genetical factors. AIMS of this study were: (1) to classify the IBD patients according the disease activity; and (2) to determine the presence of factor V Leiden mutation in IBD patients. PATIENTS AND METHODS: the observation was carried out in 49 patients with Crohn's disease (CD) and 29 patients with ulcerative colitis (UC). None of them had a history of thrombotic episodes. IBD was diagnosed by conventional clinical, endoscopic, radiological and histological criteria. The factor V Leiden mutation was detected by the polymerase chain reaction (PCR) method. Crohn's disease activity index (CDAI) was evaluated using the method of the National Cooperative Crohn's Disease Study. We determined the UC disease activity according to Truelove-Witts classification. RESULTS: The prevalence of factor V Leiden mutation was increased in both populations of the patients to compare it with healthy persons (14.28 and 27.58% vs. 5.26%, n=7/49 and 8/29 vs. 3/57). The statistical analysis did not show a significant relationship between the CDAI or the Truelove-Witts grade in UC and the presence of Leiden mutation. CONCLUSION: the presence of factor V Leiden mutation probably has a role in the development of IBD. Our results suggest a higher prevalence of this mutation in Central European patients than in Southern, Northern Europe or America, may be due to the genetical differences of these populations.

Adult↗

PubMedDate not supplied

Leiden mutation (as genetic) and environmental (retinoids) sequences in the acute and chronic inflammatory and premalignant colon disease in human gastrointestinal tract.

BACKGROUND: Tumor, calor, dolor, pallor and functio laesa are together involved in the different acute and chronic inflammatory processes. The processes involved in the inflammation are determined by differently acquired and hereditary factors. Recently the presence of a new genetic marker (Leiden point mutation) was found in Crohn's disease and ulcerative colitis. On the other hand, the GI mucosal integrity was proven on gastrointestinal mucosal damage to be produced by different chemicals, xenobiotics, drugs. In human observations, the serum level of retinoids (vitamin A, lutein, zeaxanthin, alpha-, beta-carotene) was proven in patients with chronic gastrointestinal inflammatory bowel disease. The aims of this study were (1) to measure the prevalence of Leiden mutation; (2) to identify the changes in the serum retinoid level in patients with Helicobacter pylori infection of the stomach (n=24), hepatitis C infection (n=75), ileitis terminalis (Crohn's disease; n=49), ulcerative colitis (n=35), colon polyposis (n=59) and adenocarcinoma in colon polyps (n=9), and 57 healthy persons were used in the control group; (3) to compare the directions of the changes in the measured parameters in the acute (H. pylori and hepatitis C infections), chronic (ileitis terminalis, ulcerative colitis) GI inflammatory diseases and in colon polyposis without and with malignisation. METHODS: The Leiden mutation was measured by the method of polymerase chain reaction, the retinoid level in the patient's serum was measured by high liquid cromathografic method (HPCL). RESULTS: (1) It has been found that the prevalence of Leiden mutation increased significantly in patients with ileitis terminalis (P<0.001), ulcerative colitis (P<0.001), colon polyposis (P<0.001) and with colon polyps with malignisation (P<0.01). (2) Serum level of vitamin A and zeaxantin were decreased significantly in all group of patients except for the group with H. pylori infections. (3) alpha- and beta-carotenes were found to be practically at the same level as those in the control groups, except in patients of colon polyps with malignisation. (4) The vitamin A, lutein, zeaxantin, alpha- and beta-carotenes were decreased in patients with ileitis terminalis. CONCLUSIONS: (1) The essential role of retinoids (carotenoids) as environmental factors are suggested for keeping GI mucosal integrity in human healthy subjects and patients. (2) Leiden mutation, as a genetic marker, can be used in the screening of patients with ileitis terminalis, ulcerative colitis and colon polyposis (without and with malignisation). (3) An opposite direction can be found between the increased prevalence of Leiden mutation and decrease of serum levels of retinoids in group of patients with ileitis terminalis, ulcerative colitis and colon polyposis (without and with malignisation).

Acute Disease↗

PubMedDate not supplied

Cyclin D-cdk6 complex is targeted by p21(WAF) in growth-arrested lymphoma cells.

Normal human B lymphocytes are sensitive to the growth-inhibitory action of transforming growth factor beta1 (TGFbeta1) whereas malignant B lymphoma cells are mostly resistant to TGFbeta1 effects. We examined the phosphorylation status of retinoblastoma protein and the activity of G(1) cyclin-dependent kinases (cdk) in TGFbeta1-sensitive malignant follicular lymphoma cells during the TGFbeta1 treatment. The kinase activity of cdk2, cdk4, and cdk6 was significantly reduced and hypophosphorylation of pRb on serine 795 (S795) and threonine 373 (T373) was observed. We examined the composition of cdk complexes and the level of cdk inhibitors to explain the inhibitory action of TGFbeta1 toward cdk activity. Both cdk4 and cdk6 were notably dissociated from cyclin D cofactors, while cyclin E-cdk2 complexes remained coupled in TGFbeta1-treated cells. TGFbeta1-induced growth arrest was associated with notably increased binding of p21(WAF1) to cdk4 and cdk6. No induction of cdk-inhibitor molecules of INK family was observed in TGFbeta1-treated DoHH2 cells. As shown, TGFbeta1-induced growth arrest of malignant B cells was associated with the activation of CIP/KIP family members of cdk inhibitors.

Blotting, Western↗

PubMedDate not supplied

Effect of lysine-28 side-chain acetylation on the nanomechanical behavior of alzheimer amyloid beta25-35 fibrils.

Amyloid fibrils are self-associating filamentous structures formed from the 39- to 42-residue-long amyloid beta peptide (Abeta peptide). The deposition of Abeta fibrils is one of the most important factors in the pathogenesis of Alzheimer's disease. Abeta25-35 is a fibril-forming peptide that is thought to represent the biologically active, toxic form of the full-length Abeta peptide. We have recently shown that beta sheets can be mechanically unzipped from the fibril surface with constant forces in a reversible transition, and the unzipping forces differ in fibrils composed of different peptides. In the present work, we explored the effect of epsilon-amino acetylation of the Lys28 residue on the magnitude of the unzipping force of Abeta25-35 fibrils. Although the gross structure of the Lys28-acetylated (Abeta25-35_K28Ac) and wild-type Abeta25-35 (Abeta25-35wt) fibrils were similar, as revealed by atomic force microscopy, the fundamental unzipping forces were significantly lower for Abeta25-35_K28Ac (20 +/- 4 pN SD) than for Abeta25-35wt (42 +/- 9 pN SD). Simulations based on a simple two-state model suggest that the decreased unzipping forces, caused most likely by steric constraints, are likely due to a destabilized zippered state of the fibril.

Acetylation↗

PubMedDate not supplied

Genetic variation in two conserved local Romanian pig breeds using type 1 DNA markers.

Analysis of the genetic variation of an endangered population is an important component for the success of conservation. Animals from two local Romanian pig breeds, the Mangalitsa and Bazna, were analysed for variation at a number of genetic loci using PCR-based DNA tests. Polymorphism was assessed at loci which 1) are known to cause phenotypic variation, 2) are potentially involved in trait differences or 3) are putative candidate genes. The traits considered are disease resistance, growth, coat colour, meat quality and prolificacy. Even though the populations are small and the markers are limited to specific genes, we found significant differences in five of the ten characterised loci. In some cases the observed allele frequencies were interesting in relation to gene function and the phenotype of the breed. These breeds are part of a conservation programme in Romania and marker information may be useful in preserving a representative gene pool in the populations. The use of polymorphisms in type 1 (gene) markers may be a useful complement to analysis based on anonymous markers.

Animals↗

PubMedDate not supplied

[Bronchial lesions in rheumatoid pulmonary fibrosis].

Explore the source record for details and available documents.

Arthritis, Rheumatoid↗

PubMedDate not supplied

[The characteristics of a case of Churg-Strauss syndrome (CSS)].

The authors present the case of a 35-years-old female with severe bronchial asthma non-responding to treatment, mobile infiltrative pulmonary images on chest X-ray considered and treated first as pulmonary tuberculosis smear-negative, maculo-papular skin lesions on the limbs and a high percentage of eosinophils in peripheral blood. The diagnosis was settled by histologic examination of the skin lesions. The evolution was very good with high doses of oral corticosteroids.

Adult↗

PubMedDate not supplied

Z/EG, a double reporter mouse line that expresses enhanced green fluorescent protein upon Cre-mediated excision.

The Cre/loxP system has become an important tool in designing postintegrational switch mechanisms for transgenes in mice. The power and spectrum of application of this system depends on transgenic mouse lines that provide Cre recombinase activity with a defined cell type-, tissue-, or developmental stage-specificity. We have developed a novel mouse line that acts as a Cre reporter. The mice, designated Z/EG (lacZ/EGFP), express lacZ throughout embryonic development and adult stages. Cre excision, however, removes the lacZ gene, which activates expression of the second reporter, enhanced green fluorescent protein. We have found that the double-reporter Z/EG line is able to indicate the occurrence of Cre excision from early embryonic to adult lineages. The advantage of the Z/EG line is that Cre-mediated excision can be monitored in live samples and that live cells with Cre-mediated excision can be isolated using a single-step FACS. It will be a valuable reagent for the increasing number of investigators taking advantage of the powerful tools provided by the Cre/loxP site-specific recombinase system.

Alkaline Phosphatase↗

PubMedDate not supplied

Copy number of cancer genes predict tumor grade and survival of pancreatic cancer patients.

Pancreatic cancer is on the increase. While means of early diagnosis are being sought, it continues to present late. Prognostication is based on patient and tumor characteristics, including expression or mutation of cancer-related genes. Few studies have examined the impact of the amplification of these genes on the outcome of pancreatic cancer. We have now used a non-radioisotopic slot-blot technique to relate gene copy numbers of p53, c-myc and K-ras to tumor grade and survival. Outcomes were corrected for patient characteristics, tumor location and TNM staging. The Kaplan-Meier test for likelihood of survival showed that increase in copy number of the two oncogenes and loss of p53 were associated with non-significant reduction in survival. When these variations in cancer gene copy numbers were, however, examined by logistic regression analysis in the context of patient and tumor characteristics, survival was negatively related to K-ras amplification (p = 0.0291). Tumor grade, but not survival was positively related to loss of p53 gene copy (p = 0.0131) as well as c-myc amplification (p = 0.0248). Thus using a simple non-radioisotopic technique for the detection of cancer gene copy number in association with patients and disease characteristics, we could predict survival on the one hand and tumor behavior on the other. Such information could be used to plan initial and follow-up therapy.

Adult↗

PubMedDate not supplied

Inhibition of the zymosan-induced chemiluminescence of human phagocytes by adenosine, polyadenylic acid and agents influencing adenosine metabolism.

The zymosan-induced chemiluminescence of human phagocytes (neutrophil granulocytes) could be inhibited by adenosine, polyadenylic acid, dipyridamole (an agent blocking the cellular adenosine uptake) and coformycin (a highly potent inhibitor of enzyme adenosine deaminase). It is suggested that in estimating the antianginal and antithrombotic action of dipyridamole, its action on the phagocytes should be taken into account. The same consideration would be true for 2'-deoxycoformycin (a coformycin analogue) used as a potent anticancer and immunosuppressive drug.

Adenosine↗

PubMedDate not supplied

[The epidemiology of depression].

Explore the source record for details and available documents.

Adolescent↗