Early prenatal ultrasonic detection of fetal triploidy syndrome.
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Biomedical subjects
Publications and source records attributed to A Levy.
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The National Heart, Lung, and Blood Institute, Bethesda, Md, sponsored national telephone surveys of practicing physicians and the adult public in 1983, 1986, and 1990 to assess attitudes and practices regarding high serum cholesterol levels. Each time, approximately 1600 physicians and 4000 adults were interviewed. Trends show continuing change in medical practice and public health behavior relating to serum cholesterol. In 1990, physicians reported treating serum cholesterol at considerably lower levels than in 1986 and 1983. The median range of serum cholesterol at which diet therapy was initiated was 5.17 to 5.66 mmol/L (200 to 219 mg/dL) in 1990, down from 6.21 to 6.70 mmol/L (240 to 259 mg/dL) in 1986 and 6.72 to 7.21 mmol/L (260 to 279 mg/dL) in 1983. The median ranges for initiating drug therapy were 6.21 to 6.70 mmol/L (240 to 259 mg/dL) in 1990, 7.76 to 8.25 mmol/L (300 to 319 mg/dL) in 1986, and 8.79 to 9.28 mmol/L (340 to 359 mg/dL) in 1983. The number of adults who reported having had their cholesterol level checked rose from 35% to 46% to 65% in 1983, 1986, and 1990, respectively. Between 1983 and 1990, the number of adults reporting a physician diagnosis of high serum cholesterol increased from 7% to 16%; the number reporting a prescribed cholesterol-lowering diet increased from 3% to 9%. Reports of self-initiated diet efforts reached a high of 19% in 1986 and decreased to 15% in 1990 compared with 1% in earlier years. In 1990, over 90% of physicians reported awareness and use of the recommendations from the Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, and the public reported marked increases in awareness of dietary methods to lower serum cholesterol. These changes suggest educational gains; the data also suggest areas for continued cholesterol educational initiatives.
AF102B [(+-)-cis-2-methyl-spiro(1,3-oxathiolane-5,3')quinuclidine], a structurally rigid analog of acetylcholine, was investigated in a number of neurochemical, pharmacological and behavioral tests related to cholinergic functions. AF102B induced atropine-sensitive contractions of isolated guinea pig ilea and trachea preparations with EC50 values of 3.5 and 3 microM being 87- and 1.3-fold less potent than acetylcholine, respectively. Binding studies using the radioligands pirenzepine, cis-dioxolane and quinuclidinyl benzilate in rat cerebral cortex and quinuclidinyl benzilate in cerebellar homogenates indicated that AF102B was a potent and highly selective M1-type muscarinic probe, being more selective for M1 receptors than oxotremorine, carbachol and AF102A (the trans-isomer of AF102B). AF102B had a 3-fold higher apparent affinity for M1 receptors than the prototype M1 agonist, McN-A-343, cis- and trans-AF30 (other rigid analogs of acetylcholine). Treatment of rat cortical homogenates with Cu++ ions did not modify the affinity observed for the muscarinic antagonists atropine, scopolamine and pirenzepine, whereas increasing the proportion of high affinity sites for the agonists oxotremorine-M, carbachol and McN-A-343. The apparent affinity of AF102B also increased by Cu++ treatment suggesting that this compound interacts with rat cerebral cortex muscarinic receptors as an agonist. AF102B did not affect high affinity choline transport, choline acetyltransferase and acetylcholinesterase activities in rat brain preparations. In rats treated with AF64A (the cholinotoxin ethylcholine aziridinium ion; 3 nmol/2 microliters/side i.c.v.), AF102B (1 mg/kg p.o. or i.p.), AF102A (1 mg/kg i.p.), cis-AF30 (1 mg/kg, i.p.) and physostigmine (0.06 mg/kg i.p.), each reversed cognitive impairments in a step-through passive avoidance task. Both AF102B and AF102A (1 mg/kg i.p.), but not physostigmine (0.1 mg/kg i.p.), were effective also in reversing reference memory impairments in a Morris water maze test. Repetitive administrations of AF102B (0.2 mg/kg/day i.p.) improved AF64A-induced working memory deficits in the Morris water maze test, but did not affect open field behavior. The data show that the selective M1 agonist AF102B can restore AF64A-induced cognitive impairments, without producing adverse central and peripheral side effects at the effective doses and this can indicate its potential use for the treatment of Alzheimer's disease.
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Electron paramagnetic resonance spectra of methemoglobin reveal that, in addition to the major tetragonal high-spin aqueous complex and the low-spin hydroxide complex, three other complexes associated with the interaction of the distal histidine are resolved. These are a rhombic high-spin and two classes of low-spin bis-histidine complexes. By freeze-quenching experiments it is shown that the rhombic high-spin and one of the low-spin bis-histidine complexes (B) are at equilibrium with the dominant species. Incubation in the 210-260 K temperature range shifts the total equilibrium toward a low-energy state with the distal histidine coordinated to the iron (complex C).
Since a major function of RNA polymerase must be to bring together substrates in the optimal configuration for internucleotide bond formation, studies have been undertaken to understand the geometrical relationship of the two substrates. A model has been constructed for the geometry of interaction of two ATP molecules poised on the active site of the Escherichia coli enzyme for the formation of the first bond in RNA synthesis. The model is based primarily on the distance, measured by EPR, between the two metals in the i and i + 1 subsites, as well as distances, measured by NMR, from each metal to points on the substrate in the same subsite, in the presence of a poly(dAdT).poly(dAdT) template. Both the Zn(II) in the i site and the Mg(II) in i + 1 are displaced by Mn(II). The nucleotide bases are not parallel to each other, in line with the reaction of the ATP molecules with DNA within the transcription bubble. The metal in the i site appears too far removed from substrate to participate in catalysis, but the metal in i + 1 is in position to bind to the beta- and gamma-phosphate groups and probably is involved in cleavage of the triphosphate, as has been previously suggested.
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Age-related histopathological changes in the hippocampal formation were correlated with cognitive performance, evaluated in rats at the 8-arm radial maze. Experiments were conducted using young (3 months), mature (12 months), middle-aged (17 months) and aged (24 months) Wistar rats. Significant memory impairments were already observed at the age of 12 months in all the measured parameters (correct choices, percent errors and total time). No further decline was observed between 12 and 17 months of age, while at 24 months additional decline was monitored mainly in the percent errors parameter. Morphometric analysis revealed a decrease in the area of cells within the hippocampus and the number of cells in the CA3 subfield. This pattern of morphological changes with age corresponded well with the cognitive impairments, with high correlation especially to lesions at the CA3 subfield. It had also been confirmed in this study that lipofuscin appeared to be a good histochemical marker for CNS cell degeneration. It is concluded that 12-month-old Wistar rats may serve as the animal model of choice for the study of specific age-related behavioral deficits and that the hippocampal CA3 region might play a major role in the age-dependent cognitive decline.
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We have examined the effect of orally administered bromocriptine on TSH beta-subunit messenger (m)RNA in the anterior pituitary glands of Sprague-Dawley rats using in situ and dot-blot hybridization histochemistry. Quantitative in situ hybridization of pituitary sections demonstrated a 60% reduction in TSH beta-subunit mRNA probe binding from rats fed a diet containing bromocriptine 10 mg/kg/day. This was confirmed by dot-blot analysis of nuclear and cytoplasmic pituitary extracts from the same tissue. Hybridization of cytoplasmic extracts of pituitary cells cultured under actinomycin D-induced transcription arrest showed that part of the effect of bromocriptine appeared to be mediated through a change in TSH beta-subunit mRNA stability and implies that the acute influence of dopamine on TSH metabolism may be transduced by control of TSH beta-subunit mRNA catabolism. This suggests a mechanism by which cells with relatively stable tissue specific mRNAs appear to respond rapidly to hormonal effects at the transcriptional level.
In the present study, we attempted to identify the chemical nature of the clastogenic factor (CF) from patients with progressive systemic sclerosis (scleroderma). Computerized mass spectrometry of clastogenic fractions obtained by HPLC of plasma ultrafiltrates detected molecular peaks compatible with inosine triphosphate and inosine diphosphate (ITP and IDP). The concomitant detection of IDP, together with ITP, and the absence of these peaks in nonclastogenic fractions and corresponding control fractions are arguments in favor of a biological relevance of these observations. The most important confirmation came from the clastogenic effect of commercial ITP and IDP added to the culture medium of the test cultures. The induction of chromatid type damage by these substances in lymphocytes exposed in the G0 phase of their cell cycle and the prevention of this damage by superoxide dismutase are analogous to the observations with CF.
Cognitive performance in aging Wistar rats was monitored using the radial arm maze and the latter was correlated with the density of muscarinic receptors in the CNS, using quantitative in vitro receptor autoradiography. Significant working memory deficits were observed in 12, 17 and 24-month-old rats as compared to 3-month-old animals. In addition, the number of the muscarinic receptors declined significantly with age (from 27 to 42% depending on the brain region sampled) utilising [3H]QNB and [3H]PZ receptor binding assays. The above trend became evident already at the age of 12 months. The present findings support the association of central cholinergic activity with memory processes.
This study examined the effect of a specific M1 cholinergic agonist, AF102B, on place learning of aged and young rats. Spatial reference memory was tested in the Morris Water Maze task, while spatial working memory was tested on an 8-arm radial maze. Both memory functions were impaired in aged rats compared to young animals. However, the administration of AF102B significantly reduced the age-related cognitive impairments observed in both tasks. This data supports the assertion of the "cholinergic hypothesis," namely that specific enhancement of cholinergic function may reverse geriatric cognitive deficits.
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The number of metabolic disorders associated with nonimmune hydrops fetalis is very small and includes only Gaucher disease, GM1 gangliosidosis type 1, Hurler syndrome, and mucolipidosis type I. We report another association of a nonimmune hydrops fetalis with Niemann-Pick disease as evident by electron microscopy, and wish to add this disorder to the list of conditions associated with nonimmune hydrops fetalis.
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The effect of local deep microwave hyperthermia (LDMWH) on normal and Zymosan-induced arthritis has been evaluated in 12 rabbits (24 joints). LDMWH, four treatments to each joint (twice weekly for a period of 2 wk), was generated by an antenna operating at 915 MHz for 60 min, reaching an intraarticular temperature of 42.5 +/- 0.5 degrees C. A surface cooling system was used with the microwave apparatus. Two weeks after the last treatment, all animals were sacrificed. The application of LDMWH on normal joints induced a limited proliferation of the synovial lining cells with a minimal perivascular infiltration of mononuclear and neutrophil cells. However, no histologic damage to the skin, muscles, bone, cartilage or bone marrow adjacent to the heated joints could be noted. Induction of Zymosan arthritis (2 wk before LDMWH) was characterized by pannus formation and granulomatous reaction accompanied by fibrinoid deposits and disseminated necrotic foci in the synovial intima. The LDMWH treatment on the examined arthritic joints brought about a reduction in the degree of granulomatous reaction concomitant with the appearance of some fibrocytes and fine collagen fibrils. These findings suggest that LDMWH can be safely applied, even repeatedly, without morphologic evidence of damage to any normal mesenchymal tissue. Moreover, it reduces the inflammatory process in experimentally induced synovitis.
We have studied the inositol phospholipid turnover response to thyrotrophin-releasing hormone (TRH) gonadotrophin-releasing hormone (GnRH) and arginine vasopressin (AVP) in five corticotroph and six somatotroph pituitary adenomas. GnRH (100 nM) increased inositol phospholipid turnover in five of five somatotroph adenomas tested by an average of 36.4 +/- 9.4% (mean +/- SE). In a fifth, which was too small to allow inositol phospholipid turnover to be assessed, GnRH produced a rapid increase in mean intracellular calcium ion concentration. Only one of five corticotroph adenomas responded to GnRH with an increase in inositol phospholipid turnover of 19%. In contrast, all the somatotroph and corticotroph adenomas tested (four of four and five of five respectively) increased inositol phospholipid turnover in response to AVP (100 nM), by an average of 61 +/- 11.8% and 415 +/- 186% respectively. The finding of an inositol phospholipid or intracellular Ca2+ response to thyrotrophin-releasing hormone (TRH) (100 nM) in three of five somatotroph adenomas (Ca2+ increasing from 50 to 175 nM in one and inositol phospholipid turnover increasing by 172 +/- 1.9% and 49 +/- 5.2% in two) and to GnRH in all five somatotroph adenomas concurs with the common clinical finding of paradoxical growth hormone responses to these releasing factors in patients with acromegaly. The lack of such a response in three of the four corticotroph adenomas suggests that the appearance of GnRH and TRH receptors on adenomatous pituitary cells is not common to all cells.