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Biomedical subjects

A Levy

Publications and source records attributed to A Levy.

At least 217 records · Page 12Linked to original sources

Transferable clastogenic activity in plasma from persons exposed as salvage personnel of the Chernobyl reactor.

Clastogenic factors were first described in the plasma of people who had been accidentally or therapeutically irradiated. They were found also in A-bomb survivors, where they persisted for many years after the irradiation. The present study searched for these factors in the plasma of 32 civil workers from Armenia, who had been engaged as "liquidators" around the Chernobyl atomic power station in 1986. It also included 15 liquidators who had emigrated from the ex-Soviet Union to Israel. Reference plasma samples were obtained from 41 blood donors from the Armenian Blood Center in Yerevan. The samples were tested for their clastogenic activity in blood cultures from healthy donors. The majority of results from the liquidators exceeded those from the unexposed reference samples. The samples from the first Armenian group, with the higher average irradiation dose (0.6 +/- 0.6 Gy), were more clastogenic than those from the second group exposed to 0.2 +/- 0.2 Gy. The number of aberrations in the test cultures was 17.9 +/- 2.9% and 10.5 +/- 3.8% respectively, compared to 5.7 +/- 3.2% in the cultures exposed to the reference ultrafiltrates from Armenian blood donors. The samples from the Israeli liquidators also induced significantly increased aberration rates (14.0 +/- 3.9% aberrant cells). The clastogenic activity was regularly inhibited by superoxide dismutase, indicating that the chromosome-damaging effects of radiation-induced clastogenic factors are exerted via the intermediation of superoxide radicals, as is known for clastogenic factors of different origin.

Accidents↗

A survey of non-cardiac fetal intrathoracic malformations diagnosed by ultrasound.

Between November 1986 and April 1993, 22 cases of intrathoracic abnormality were detected prenatally by ultrasound, and examined postnatally. There were 11 cases of diaphragmatic hernia, 5 cases of cystic adenomatoid malformation of lung, one case of chylothorax, two cases of lung sequestration, and three cases of bronchogenic cyst. The total number of deliveries during that period was 48,281 and the total number of major anomalies at that time was 669 (1.38%). Cases of hydrothorax of various etiology, as well as thoracic cage anomalies were excluded. Prenatal diagnosis allows planned delivery and the assembly of neonatologists and pediatric surgeons.

Adenomatosis, Pulmonary↗

Hypobaric hypoxia impairs spatial memory in an elevation-dependent fashion.

The effects of various levels of hypobaric hypoxia, exposure to reduced atmospheric pressure, on spatial memory in rats were examined. Hypobaric hypoxia simulates high altitude conditions where substantial deficits in human cognitive performance occur. However, few studies have measured cognitive changes in animals during exposure to this type of hypoxia. Male Fischer 344 rats were tested in the learning set version of the Morris water maze, a test known to assess spatial memory. Rats were tested at 2 and 6 hours while exposed to a range of simulated altitudes: sea level, 5500 m, 5950 m, and 6400 m. Altitude exposures at 5950 or 6400 m decreased both reference and working memory performance, as demonstrated by latency, distance, and speed measures, in an elevation-dependent fashion. During sea level testing on the day following hypobaric exposure, decrements in reference memory were still observed on all dependent measures, but only speed was impaired on the working memory task. These results agree with human studies that demonstrate elevation-dependent impairments in spatial memory performance during exposure to hypobaric hypoxia. The deficits may be attributable to changes in hippocampal cholinergic function.

Altitude↗

The aftermath of captivity: an 18-year follow-up of Israeli ex-POWs.

This is an 18-year follow-up of 164 former prisoners of war (POWs) and 190 controls. The study examined long-term morbidity, psychophysiological complaints, and illness-related behaviors. Psychophysiological complaints were found to be significantly higher among the POWs than among the controls. A significant association was also found between such complaints and symptoms of posttraumatic stress disorder (PTSD). The individual's degree of impairment was associated with both objective and subjective characteristics of captivity. The authors outline differences in types of illness observed in POWs in the current study and in studies conducted in other countries, and consider the implication of characteristics of captivity and culture.

Adult↗

Transdermal physostigmine in the treatment of Alzheimer's disease.

Physostigmine has been reported to improve the memory function of some patients with Alzheimer's Disease (AD). However, the drug has a short half-life and a narrow therapeutic window. To overcome these impediments, we developed a continuous transdermal delivery system and tested it for 2 weeks in 12 AD inpatients, using a single-blind design. No major adverse effects were recorded in any of the patients. Physostigmine plasma concentrations were relatively stable (0.56 +/- 0.10 ng/ml) and correlated well with blood acetylcholinesterase inhibition. Six of the 12 patients reported improved vigilance and concentration, and also had higher scores in all four neuropsychological tests employed (Mini Mental State examination, Short Mental Test [SMT], Wechsler's Memory Scale [WMS], and Buschke's Selective Reminding Test). The performance of two additional patients improved in only two tests (SMT and WMS). Transdermal delivery of physostigmine appears to be safe and may be useful for the treatment of a subset of AD patients.

Administration, Cutaneous↗

p53 gene mutations in pituitary adenomas: rare events.

OBJECTIVE: Occult pituitary adenomas are said to occur in up to 20% of random autopsy examinations, yet the only oncogene known to be associated with pituitary adenomas, gsp, is found in only 40% of somatotrophinomas, a subtype that accounts for a minority of pituitary tumours. Mutations of the p53 tumour suppressor gene are thought to be involved in the pathogenesis of as many as 50% of all human cancers, including tumours of the central nervous system. The objective of this study was to determine whether p53 gene mutations are associated with pituitary adenomas. DESIGN AND PATIENTS: Fragments of pituitary adenoma tissue from 29 patients undergoing routine hypophysectomy for pituitary tumour were coated in cryostat embedding medium and frozen at -80 degrees C within 24 hours of resection. They consisted of 9 somatotroph, 4 corticotroph, 1 mammotroph and 15 endocrinologically inactive adenomas, all of the non-invasive clinical phenotype. Sequential frozen sections were subjected to in situ hybridization analysis for anterior pituitary hormone transcripts and examined histologically to ensure that the frozen sections used to generate DNA templates for polymerase chain reaction amplification were not contaminated with non-tumour tissue. MEASUREMENTS: p53 exons 7 and 8, within which 98% of substitution mutations are thought to occur, and exons 4-6 in tumours immunopositive for p53, were amplified by polymerase chain reaction and ligated into the vector pCR2. DNA from small-scale plasmid preparations of pCR2 containing cloned p53 exons from human pituitary adenomas was sequenced using an automated fluorescence-based system (DuPont Genesis 2000) and compared with wild-type sequence. Apparent mutations were confirmed or refuted by sequencing a further 2-4 clones isolated from the same template. RESULTS: Although immunocytochemical staining patterns for wild-type p53 varied markedly between different tumours, no mutations were identified in any of the exonic sequences examined. CONCLUSIONS: p53 mutations, at least within the high mutation domains of p53, occur infrequently in human pituitary adenomas. Increased steady-state levels of p53 protein identified immunocytochemically may be a consequence of binding to other cellular proteins in these tumours.

Adenoma↗

Control of canine gastric emptying of fat by lipolytic products.

Dietary fat is ingested in three forms: 1) in solid food, 2) as aqueous emulsions, and 3) as unemulsified, liquid oil. On the basis of a scant previous literature, we postulated that liquid fat (emulsions or oils) would empty from the stomach at speeds that varied with the amounts ingested but that this dynamic would be modulated by feedback inhibition from lipolytic products. To test these ideas, we used a gamma camera to track gastric emptying of 123I-labeled fat in dogs with chronic pancreatic fistulas by which lipase was excluded from or replenished in the duodenum in varied amounts after dogs were fed 15-, 30-, and 60-g loads of liquid fat given with solid foods or as emulsions. We also tracked concurrent gastric emptying of 113mIn, which marked the solid food phase or the water phase of emulsions. In some studies, we used a potent and specific inhibitor (orlistat) of pancreatic and gastric lipases to assess how lipolytic products modulated emptying of liquid fat. In the absence of pancreatic enzymes, both oils and emulsions emptied initially at high speeds that varied with fat loads, but emptying slowed 20 min after ingestion of emulsions and 60 min after ingestion of unemulsified oil. Studies with orlistat indicated that these changes in rates resulted from liberation of gastric lipolytic products. Emptying of oil emulsions was not altered by duodenal replenishment with pancreatic enzymes, but emptying of unemulsified oil was inhibited in a dose-related fashion, such that maximal inhibition was achieved when pancreatic enzymes were replenished at > or = 40% of normal amounts. Studies with orlistat confirmed that this dose-dependent slowing was due specifically to lipase. Emptying of solid food was much more sensitive to replenishment with enzymes, so that a 10% replenishment maximally inhibited solid emptying.

Animals↗

Thyroid hormone-mediated regulation of corticotropin-releasing hormone messenger ribonucleic acid in the rat.

We have used in situ hybridization histochemistry to investigate interactions between the thyroid and adrenal axes in the rat. Propylthiouracil (PTU)-induced hypothyroidism caused a significant reduction in CRH gene transcripts in the paraventricular nucleus of male rats, with a concomitant decrease in both POMC gene expression in the anterior pituitary gland and circulating corticosterone. Conversely, adrenalectomy alone or adrenalectomy with high dose corticosterone pellet replacement had no significant effect on the thyroid hormone axis. The effect of thyroid hormones on the adrenal axis was not secondary to changes in the level of circulating corticosteroids, as the same effect of PTU-induced hypothyroidism was seen in adrenalectomized rats given corticosterone replacement. Neither was the effect of PTU simply the result of a direct toxic effect on the hypothalamus, as concurrent treatment with T3 blocked the response. We conclude that circulating levels of thyroid hormones have a major effect on the central regulation of the hypothalamic-pituitary-adrenal axis.

Adrenalectomy↗

Pituitary ATP receptors: characterization and functional localization to gonadotropes.

We have used real-time dynamic video imaging of Fura-2 fluorescence to study the acute effects of extracellular ATP on [Ca2+]i in pituitary cells and found that ATP produced a rapid biphasic cytosolic Ca2+ increase in a dose-dependent manner in both rat pituitary gonadotropes and gonadotrope-derived alpha T3-1 cells. Removal of extracellular Ca2+ only attenuated the plateau phase of ATP-induced intracellular Ca2+ response and suramin (100 microM), a P2-purinoceptor antagonist, reduced the ATP effect by 40-60%. Further studies revealed the following rank-order of agonist potency in the Ca2+ response: -ATP = ADP = UTP > 2-methylthioATP >> beta, gamma-methylene ATP/alpha,beta-methylene ATP. Both homologous and heterologous desensitization occurred with ATP and UTP and these did not have additive effects. Together the data suggest that the intracellular Ca2+ responses of gonadotropes and alpha T3-1 cells to these nucleotides are mediated by a single class of receptor pharmacologically characterized as the P2U subtype. This is the first demonstration of functional ATP receptors in pituitary gonadotropes.

Animals↗

Expression of chorionic gonadotrophin in human pituitary adenomas.

In addition to the classical anterior pituitary hormones, many human pituitary adenomas express hormone genes ectopically. Expression of glycoprotein hormone alpha-subunit and, less commonly, free luteinizing hormone beta (LH-beta) or follicle-stimulating hormone beta is characteristic of endocrinologically inactive adenomas, a subgroup thought to be derived predominantly from the gonadotroph line. Thyrotrophin beta expression in these tumours is unusual, and specific chorionic gonadotrophin beta (CG-beta) expression, identified using oligonucleotide probes that reliably distinguish LH-beta and CG-beta in situ, is not well described. Using in situ hybridization histochemistry with a CG-beta transcript-specific oligonucleotide probe and a non-specific LH/CG-beta oligonucleotide and riboprobe, we have demonstrated specific CG-beta expression in two of 35 random pituitary adenomas; LH-beta expression occurred in a further eight adenomas. Unlike prolactin, growth hormone and proopiomelanocortin, which are transcribed in the vast majority of cells in their respective hormone-positive tumour subtypes, the pattern of LH/CG-beta was typically a scattering of single or small clusters of hormone-positive cells in a predominantly LH/CG-beta-negative tumour. Finally, although bona fide CG-beta expression in human pituitary adenomas does occur, it is only at an incidence similar to that described for carcinomas of other tissues.

Adenoma↗

Weight control practices in adults: results of a multistate telephone survey.

In this study, data collected in 1989 in a random-digit dialing telephone survey of 60,590 adults in 38 states and the District of Columbia were analyzed. Approximately 38% of women and 24% of men reported that they were currently trying to lose weight. Methods reported were counting calories (24% of women, 14% of men), participating in organized weight loss programs (10%, 3%), taking special supplements (10%, 7%), taking diet pills (4%, 2%), and fasting for 24 hours or longer (5%, 5%). Among both sexes, only half of those trying to lose weight reported using the recommended method of caloric restriction combined with physical activity.

Adolescent↗

Real time computerized intracellular calcium ion imaging: a rapid method of neuronal receptor evaluation.

Real time computerized intracellular calcium ion analysis using fura-2-based fluorescence imaging has been used to evaluate neurotransmitter receptor function in primary cultures of rat hypothalamic neurons and a rat hypothalamic neuronal cell line (LT6/4). A wide range of neurotransmitters induced an increase in intracellular Ca2+ in cultured hypothalamic neurons. In contrast, undifferentiated LT6/4 cells failed to response to 56mM K+ or to a battery of neurotransmitters with the exception of histamine (100microM). LT6/4 cells, induced to differentiate by prior exposure to dibutyryl cAMP and NGF, responded to K+ but lost their responsiveness to histamine. Computerized imaging allowed the intracellular Ca2+ response of up to 50 cells to be determined simultaneously without resort to complex electrophysiological manipulations or receptor binding studies. The assessment of receptor complement and coupling using this technique allows large amounts of reproducible data to be rapidly collected from small populations of cells.

Animals↗

Nimodipine prevents the in vivo decrease in hippocampal extracellular acetylcholine produced by hypobaric hypoxia.

Hypoxia decreases acetylcholine (ACh) synthesis and release in vitro, and ACh synthesis in vivo; however, its effect on extracellular concentration of ACh in vivo is not known. The calcium channel blocker nimodipine is a cerebrovascular dilator which also increases extracellular ACh in vivo. Therefore, it may provide protection from the effects of hypobaric hypoxia on the cholinergic system either via its effects on vascular function or by direct action on the nervous system. This study examined the effect of hypobaric hypoxia on extracellular ACh and choline levels, as measured by microdialysis, as well as the effects of nimodipine under hypoxia. Microdialysis guide cannulae were implanted into the hippocampal region of male Fischer rats so that probes would sample from the CA1 and DG regions. Animals were then exposed for eight hours to a simulated altitude of 5,500 m (18,000 ft) or tested at sea level for an equivalent duration. HPLC with electrochemical detection was used for analysis of the dialysates. At 5,500 m extracellular ACh levels in the placebo-treated group were significantly lower than the sea level group values. This decrement was reversed by nimodipine administered i.p. immediately preceding altitude ascent (10 mg/kg) and 250 min post-altitude ascent (10 mg/kg). These data suggest that nimodipine may provide protection from the detrimental effects of hypoxia on hippocampal cholinergic function.

Acetylcholine↗

[Early ultrasonic diagnosis of conjoined twins].

Conjoined twins is a rare congenital malformation occurring in 1:30,000-1:100,000 live births. Its early prenatal detection was extremely rare prior to the introduction of obstetric ultrasonography. We report 3 cases of early ultrasound diagnosis of conjoined twins at 9, 15 and 19 weeks of pregnancy, respectively. The diagnosis at 9 weeks of gestation was made via the transvaginal approach, and to the best of our knowledge is the earliest diagnosis reported in the English literature. In all 3 cases the fetuses were of the thoraco-omphalopagus type and had a shared heart. Pregnancy was discontinued in all 3 cases using methods appropriate for the first and second trimesters of pregnancy.

Abortion, Therapeutic↗