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Biomedical subjects

A Block

Publications and source records attributed to A Block.

At least 37 records · Page 2Linked to original sources

Complexity and scaling properties of amacrine, ganglion, horizontal, and bipolar cells in the turtle retina.

In the present study we have evaluated the complexity and scaling properties of the morphology of retinal neurons using fractal dimension as a quantitative parameter. We examined a large number of cells from Pseudemys scripta and Mauremys caspica turtles that had been labeled using Golgi-impregnation techniques, intracellular injection of Lucifer Yellow followed by photooxidation, intracellular injection of rhodamine conjugated horseradish peroxidase, or intracellular injection of Lucifer Yellow or horseradish peroxidase alone. The fractal dimensions of two-dimensional projections of the cells were calculated using a box counting method. Discriminant analysis revealed fractal dimension to be a significant classification parameter among several other parameters typically used for placing turtle retinal neurons in different cell classes. The fractal dimension of amacrine cells was significantly correlated with dendritic field diameters, while the fractal dimensions of ganglion cells did not vary with dendritic field span. There were no significant differences between the same cell types in two different turtle species, or between the same types of neurons in the same species after labeling with different techniques. The application of fractal dimension, as a quantitative measure of complexity and scaling properties and as a classification criterion of neuronal types, appears to be useful and may have wide applicability to other parts of the central nervous system.

Animals↗

Annexin VI, a marker protein of hepatocytic endosomes.

Three highly purified endosomal fractions from rat liver were used to purify and characterize a major protein of endosomal membranes. Intravenously injected ligands, which are taken up via receptor-mediated endocytosis, accumulate first in the fraction of intermediate density, the compartment of uncoupling of receptors and ligands. The high density membranous fraction is highly enriched in a receptor recycling compartment. The endosomal fraction of lowest density is composed of multivesicular bodies, which appear to be the immediate prelysosomal compartment. The most prominent membrane protein of these endosomes is one of 68 kDa, as revealed by silver and Coomassie Brilliant Blue staining of SDS-gel electrophoretograms. This protein dominates profiles obtained from purified membranes of the compartment of uncoupling of receptors and ligands, multivesicular bodies, and receptor recycling compartment, but is greatly reduced in those obtained from plasma membranes and lysosomes. The 68-kDa protein was purified from endosomes and digested with trypsin, and cleavage products were analyzed by protein sequencing. The tryptic fragments of the endosomal 68-kDa protein share 96% identity with corresponding sequences of mouse annexin VI and 91% identity with sequences of human annexin VI. Using immunoblots, high concentrations of annexin VI with an apparent molecular mass of 68 kDa were detected in endosomal membranes by specific antiserum to annexin VI. Significant amounts of annexin VI were also detected in Golgi membranes. Yet, the concentration was substantially lower than that of the three endosomal fractions. The association of annexin VI with endosomal membranes is calcium-dependent, as revealed by the complete solubilization from endosomal membranes by EGTA. Incubation of intact endosomes with Pronase leads to a complete degradation of annexin VI without any detectable disintegration of proteins localized on the luminal surface of endosomal membranes. Evidently, annexin VI is localized on the cytoplasmatic leaflet of the membrane of endosomes and may be of significance for their intracellular trafficking.

Amino Acid Sequence↗

Reduction of cerebral blood flow with induced tachycardia in rats and in patients with coronary artery disease and premature ventricular contractions.

A reduction of cerebral blood flow (CBF) was observed in experimental studies in rats immediately after the onset of parasystolic rhythm or with stable, but haemodynamically compromising, tachycardias. Based on these data and with a view to studying the effects of premature ventricular contractions (PVCs) on the cerebral circulation in humans, CBF was measured using the 133-Xenon inhalation method in 24 age matched human controls (group A1: age 58.5 +/- 6.2 years; group A2: 52.2 +/- 7.8 years) in nine coronary artery disease (CAD) patients without PVCs (B), in 11 CAD patients with frequent PVCs (> 300.h-1) (C) and in nine patients, after exclusion of CAD by angiography, also with frequent PVCs (> 300.h-1) (D). Holter monitoring was performed during the CBF measurement. CBF determined in the human control groups A1 and A2 was 79.9 +/- 9.9 ml.100 g.-1 min-1 and 81.5-13.0 ml. 100 g-1 min-1, respectively. CBF was 74.1 +/- 13.6 ml . 100 g.-1 min-1 (P = 0.267 vs A1) in group B, 65.8 +/- 11.8 ml.100 g-1 min-1 (P = 0.004 vs A1) in group C and 74.2 +/- 15.6 ml.100 g.-1 min-1 (P = 0.218 vs A2) in group D. The significant reduction of CBF in CAD patients with frequent PVCs suggests that arrhythmias have a significant impact on CBF. Non-CAD patients with frequent PVCs did not show significant CBF decreases in comparison with controls. One can hypothetize that an impairment of electrical postextrasystolic potentiation, due to premature ventricular depolarization, and hence myocardial dysfunction leads to CBF reduction in CAD patients. The CBF reduction with CAD could also reflect concomitant coronary and cerebral arteriosclerosis.

Aged↗

[Cerebral circulation in patients with dilated cardiomyopathy and aortic valve diseases].

The present study was performed in order to investigate the effect of dilated cardiomyopathy and severe aortic valve disease on cerebral blood flow. Cerebral perfusion was determined in 39 healthy volunteers representing two control groups of different age (77.7 +/- 8.7; 79.7 +/- 8.1 ml/100 g/min), in 7 patients with dilated cardiomyopathy (64.0 +/- 4.7 ml/100 g/min), in 11 patients with severe aortic stenosis (71.1 +/- 14.8 ml/100 g/min), and in 6 patients with severe aortic regurgitation (54.6 +/- 5.8 ml/100 g/min). Regional cerebral blood flow was measured with the 133Xenon inhalation method. Cerebral blood flow in severe aortic regurgitation patients (p = 0.006) was markedly and significantly reduced versus controls, whereas in dilated cardiomyopathy patients (p = 0.197) and in patients with severe aortic stenosis (p = 0.111) cerebral blood flow was not significantly reduced. A chronic adaptation of cerebral blood flow to the profound reduction of cardiac output is assumed in dilated cardiomyopathy patients. The collapsing pulse and the maximal reduction of mean arterial blood pressure in severe aortic regurgitation patients cause the reduction of autoregulatory capacity of cerebral blood flow with subsequent decrease of brain perfusion. Measurement of cerebral blood flow appears to be suitable for evaluation of perfusion deficits due to cardiac abnormalities. It provides an additional parameter for estimating the indication of valve replacement in patients with aortic valve disease.

Adult↗

[Intermittent focal cerebral ischemia in hypotension due to pacemaker syndrome].

A pacemaker syndrome manifested as transient sensoric aphasia in a 68-year-old woman with a VVI-pace-maker implanted after SA-block. The attack occurred during long-term blood pressure recording and Holter monitoring. Borderline hypotension was documented during ventricular pacing which induced a retrograde excitation of the atrium. Clinical investigations excluded any intracranial abnormality, any source of embolism or stenosis of extra- and intracranial cerebral arteries. Cerebral blood flow measurements revealed a significant increase during pacing at elevated heart rate. Therefore, a device for AV-sequential pacing was implanted and basic pacing rate was elevated. The present case report indicates that focal and not only global cerebral ischemia can be produced by an impairment of systemic hemodynamics due to hypotension and a pacemaker syndrome. Improvement of cerebral blood flow during pacing is an unexpected finding contrasting with the concept of autoregulation. In addition, pacemaker implantation should be discussed in patients with transient cerebral perfusion deficits if an improvement of cerebral blood flow is documented along with rising heart rate.

Aged↗

Chromosome aberrations in lymphocytes from women irradiated for benign and malignant gynecological disease.

Excess leukemias have occurred after partial-body radiotherapy for cervical cancer and benign gynecological disease (BGD). However, the level of risk is nearly the same in both groups, about twofold, despite a tenfold difference in average dose to active bone marrow (8 Gy vs 0.7 Gy, respectively). High-dose cell killing has been postulated as one explanation for this apparent inconsistency. To examine whether chromosome aberration rates observed in lymphocytes many years after exposure might serve as population markers of cancer risk, blood samples were taken from 60 women treated for BGD (34 with radiation) and cytogenetic data compared with previous results from 96 women irradiated for cervical cancer. Remarkably, the rate of stable aberrations, which reflects nonlethal damage in surviving stem cells, was only slightly higher among the cancer patients. Thus the lower-dose regimens to treat benign disorders resulted in much higher aberration yields per unit dose than those for cervical cancer. Assuming that the fraction of cytogenetically aberrant stem cells that survive radiotherapy contributes to the leukemogenic process, these data are then consistent with the epidemiological observations of comparable overall leukemia risks seen in these two irradiated populations. Accordingly, for patient populations given partial-body radiotherapy, stable aberrations at a long time after exposure appear to serve as biomarkers of effective risk rather than as biomarkers of radiation dose received.

Aged↗

[Effect of frequent ventricular extrasystole on brain circulation in patients with coronary heart disease].

Animal experiments using the microsphere method indicate a 8% reduction of mean cerebral blood flow during parasystolic rhythm induced by ventricular pacing in comparison to a control group with sinus rhythm. The parasystolic rhythm causes changes of systemic arterial blood pressure, which are comparable to the hemodynamic effects of frequent premature ventricular contractions. Because a reduction of cerebral blood flow induced by frequent premature ventricular beats can be assumed by the results of the laboratory investigations, cerebral blood flow was determined in a clinical study in 19 coronary artery disease patients and in 11 healthy, age-adjusted volunteers using the 133Xenon-inhalation method, in order to investigate the effect of ventricular ectopics on cerebral perfusion. Simultaneously Holter monitoring was performed during cerebral blood flow measurements. Cerebral blood flow was estimated by the initial slope index, which is calculated from the early decay of the clearance curve, and by the mean cerebral blood flow index, which is calculated by the stochastic method. Grey matter blood flow is estimated by the two-compartment analysis. Cerebral blood flow in coronary artery disease patients is reduced versus controls. The initial slope indices were 45.2 +/- 5.1 s-1 and 57.4 +/- 7.2(-1), respectively (p < 0.01). In patients with frequent ventricular ectopic activity (739/h) an additional reduction of cerebral blood flow was observed. The initial slope index was 42.6 +/- 6.3 s-1 (p < 0.01). The reduction of cerebral blood flow in coronary artery disease patients is partially due to the coincidence of coronary and cerebral artery disease. Frequent ventricular premature contractions might cause an additional reduction.

Adult↗

Hereditary sensory radicular neuropathy: defective neurogenic inflammation.

Hereditary sensory radicular neuropathy exhibits autosomal dominant inheritance with complete penetrance in males and incomplete penetrance in females. Newer tests of small sensory nerve function were used in screening 8 family members aged between 14 and 66 years. All exhibited some frequent features of the disorder with an onset in the 2nd or 3rd decade, foot ulceration, foot callus, loss of pin prick, thermal and light touch sensation, and some reduction in vibration acuity and proprioception in the lower limbs. The hands were involved in 3 of 8, muscle involvement was present in 5 of 8, but deafness was not detected by audiometry. Nerve conduction velocity, sensory action potentials, latency and amplitude, thermal acuity, vibration acuity and axon reflex flares were measured in all patients. One sural nerve biopsy confirmed the presence of peripheral fibre loss in this predominantly sensory neuropathy. Chemically evoked axon reflex tests were used to evaluate the extent of primary sensory nerve fibre involvement. All patients were tested using a Moor MBF 3-D dual channel laser Doppler velocimeter. Acetylcholine or phenylephrine iontophoretically applied as 16 mC doses evoked absent or tiny axon reflexes in areas of impaired pin prick sensation. By contrast, direct microvascular dilator responses to nitroprusside (smooth muscle dependent) and acetylcholine (endothelium-dependent) were present but somewhat reduced in areas with defective neurogenic inflammation. These results differ significantly from the responses obtained in age-matched healthy controls (P < 0.05). Foot pressure analysis was performed for orthoses in 2 affected members with foot ulceration using the Musgrave Footprint system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Light-inducible and constitutively expressed DNA-binding proteins recognizing a plant promoter element with functional relevance in light responsiveness.

Four cis-acting elements, designated as Boxes I, II, III and IV, have previously been identified as functionally relevant components of the light-responsive chalcone synthase (CHS) promoter in parsley (Petroselinum crispum). This paper describes the isolation of three cDNAs encoding proteins which bind specifically to Box II, one of two cis-acting elements found within a 52 bp CHS promoter region shown here to be sufficient for light responsiveness in parsley. The deduced amino acid sequences of all three proteins reveal conserved basic and leucine zipper domains characteristic of transcription factors of the bZIP class. Nucleotide sequences recognized by these factors contain an ACGT motif common to many cis-acting elements. Therefore, we have termed the proteins CPRF-1, -2 and -3 (Common Plant Regulatory Factor). The characteristics of CPRF-1 binding to Box II and the timing of transient CPRF-1 mRNA accumulation during light exposure of previously dark-grown parsley cells are consistent with the hypothesis that this factor participates in the light-mediated activation of the CHS gene in parsley.

Acyltransferases↗

Regulatory elements required for light-mediated expression of the Petroselinum crispum chalcone synthase gene.

Chalcone synthase (CHS) catalyzes the committed enzymatic step in flavonoid biosynthesis. In parsley (Petroselinum crispum), CHS is encoded by a single gene locus. Transcriptional activation of the gene in response to UV-containing white light has been demonstrated. Analysis of the CHS gene promoter by in vivo footprinting revealed four short sequences, designated Boxes I, II, III, and IV, which contain guanosine residues with altered reactivity to the methylating agent dimethylsulfate in UV-treated versus untreated parsley cells. Studies were performed to characterize the functional components of the CHS gene promoter using a parsley protoplast transient expression system. By deletion and block-mutation analyses it was shown that Boxes I and II act together as a cis-acting unit and are necessary components of the minimal, light-responsive CHS gene promoter. The Box II sequence, which is similar to the conserved G Box sequence defined in promoters of ribulose 1,5-bisphosphate carboxylase small subunit (RBCS) genes, has been subjected to detailed analysis by site-directed mutagenesis. The heptameric sequence 5'-ACGTGGC-3' has been defined as the critical core of Box II required for light induction in the context of the CHS gene minimal promoter. Box II is functionally equivalent to a second, sequence-related element (Box III) that can replace Box II in an orientation-dependent manner. Chimaeric promoter-fusion constructs to the GUS reporter gene demonstrated that Boxes I and II, together constituting a cis-acting unit, are necessary and sufficient for light-mediated activation of the CHS gene promoter.

Acyltransferases↗

Functional borders, genetic fine structure, and distance requirements of cis elements mediating light responsiveness of the parsley chalcone synthase promoter.

The genetic fine structure of cis-acting sequences previously shown to be necessary for light-regulated expression in the promoter of the parsley (Petroselinum crispum) chalcone synthase gene was analyzed. Site-directed mutations and changes in spacing between cis elements were measured in transient expression assays in parsley protoplasts. Clustered point mutations allowed assignment of functional borders. Single-base substitutions within a highly conserved cis element (box II/G box) defined a critical core of seven bases, 5'-ACGTGGC-3'. It is functionally equivalent to a second sequence-related element (box III), which could replace box II in an orientation-dependent manner. The activity of box II required the presence of another juxtaposed element (box I) at a defined distance. No distance requirement was observed between the two large separable promoter regions known to independently confer light-regulated expression. These data support our hypothesis that a cis-acting sequence that is present in a limited number of diversely regulated plant genes gains its functional capacity and specificity by combinatorial diversity involving flanking partner elements.

Acyltransferases↗

Cytogenetic study of maturing granulocytes in bone marrow of patients with acute myelogenous leukemia.

To determine the cytogenetic origin of maturing granulocytes in the bone marrow of patients with acute myelogenous leukemia, bone marrow cells were studied using a modified cytogenetic technique, which does not disrupt the cell membrane, in conjunction with periodic acid-Schiff (PAS) staining. In four cases successfully studied, myeloblasts were PAS-negative and granulocytes were PAS-positive. In three cases successfully studied following 0-2 days of culture, metaphase spreads with abnormal karyotypes characteristic of the patients' leukemic clones were seen in five of five, six of nine, and four of four PAS-positive cells successfully studied. These patients' bone marrows were AN, AA, and AA, respectively, by standard cytogenetic study. Therefore, the cytogenetic status of PAS-positive cells did not necessarily correlate with presence or absence of normal metaphases determined by standard cytogenetic study. Bone marrow cells which underwent full and partial granulocytic maturation in suspension culture were studied following 2 weeks of culture. Abnormal karyotypes were seen in five of five and two of two metaphases in PAS-positive cells successfully studied in two patients. Therefore, we have demonstrated that when acute myelogenous leukemia cells undergo myeloid maturation in culture, the mature cells may be definitely proven to derive from leukemic progenitors rather than from normal stem cells.

Adult↗

Arachidonate synthesis and uptake in isolated guinea-pig megakaryocytes and platelets.

Arachidonic acid (20:4) synthesis and uptake were studied in guinea-pig megakaryocytes and platelets. Isolated megakaryocytes and platelets were incubated with [3H]20:4, 8,11,14-[14C]eicosatrienoic acid (gamma-20:3) and [14C]linoleic acid (18:2) and their lipids were analyzed for radioactivity. The study showed that there was 0.153 microM of unesterified 20:3 and 0.237 microM of 20:4 in guinea-pig plasma in nonfasting animals. At these concentrations, 42.6 pmol of gamma-20:3 and 53.3 pmol of 20:4 were taken up per h per 10(5) megakaryocytes in vitro. Megakaryocytes desaturated 27% of the gamma-20:3 to 20:4 but could not desaturate 18:2. Platelets could not desaturate gamma-20:3 or 18:2. In megakaryocytes, the distribution of 20:4 synthesized by the desaturation of gamma-20:3 and 20:4 taken up reflected the endogenous distribution of 20:4 in megakaryocyte phospholipids and 20:4 was predominantly incorporated into phosphatidylethanolamine (PE). In contrast, the distribution of [3H]20:4 taken up into platelets did not reflect the endogenous distribution. 20:4 was primarily incorporated into platelet phosphatidylcholine and phosphatidylinositol. The study showed that megakaryocytes but not platelets possess a delta 5 desaturase and can synthesize 20:4 from gamma-20:3. Neither cell was shown to have a delta 6 desaturase. Megakaryocytes appear to have the capacity to determine the composition of all pools of platelet 20:4 either by uptake or synthesis of 20:4. Platelets, most likely, have a limited capacity to alter structural pools of 20:4 contained primarily in PE and phosphatidylserine (PS).

8,11,14-Eicosatrienoic Acid↗

Studies of mitomycin C absorption after intravesical treatment of superficial bladder tumors.

Mitomycin C is an active drug in the treatment of superficial bladder cancer. Although clinical safety of intravesical mitomycin C has been well accepted there are no data on absorption of this drug from the bladder in patients with damaged bladder mucosa. We studied 18 patients for evidence of absorption of mitomycin C after transurethral resection and/or radiation therapy. Mitomycin C is absorbed on intravesical instillation and the degree of absorption depends on the degree of damage to the bladder. Despite some evidence of absorption no systemic effect on bone marrow was observed and no evidence of deoxyribonucleic acid damage was found in any of these patients. Mitomycin C appears to be a safe drug but further studies are indicated to document its safety when used for maintenance therapy.

Antibiotics, Antineoplastic↗