Biomedical subjects

A Levy

Publications and source records attributed to A Levy.

At least 91 records · Page 5Linked to original sources

PubMed1999

The effects of age and spontaneous adenoma formation on trophic activity in the rat pituitary gland: a comparison with trophic activity in the human pituitary and in human pituitary adenomas.

The effects of ageing on trophic activity in the pituitary gland and the molecular events that underlie pituitary tumour formation are poorly understood. In the present study we have used an extremely accurate system to analyse trophic activity in human pituitary tumours and compared our findings with trophic activity in spontaneous rat pituitary adenomas and with changes in basal rates of turnover as the animals age. Thin, hematoxylin and eosin-stained pituitary sections from groups of male Wistar rats aged 6 weeks to 16 months, killed at 90-min intervals after receiving a single intraperitoneal bolus of colchicine to block cellular passage through mitosis, were evaluated histologically. Extremely accurate quantification of small changes in the prevalence of trophic events, and thus the rate of cell turnover, was achieved using a dedicated computerized aid to manual cell counting. Results were compared with the prevalence of mitotic activity in 24 spontaneous rat pituitary adenomas and with a series of 97 archival human pituitary adenomas and 24 normal human pituitary glands obtained at autopsy. In rats, average basal pituitary cell turnover declined by over 95% between 6 weeks and 16 months of age. Concurrent with this decline was a marked increase in the prevalence of adenoma formation. The prevalence of mitotic activity in spontaneous rat pituitary adenomas averaged almost twice that seen in normal, young rat pituitary and exceeded 16 times that seen in the pituitary of aged animals. In contrast, when compared to normal human pituitary tissue, average trophic activity in human pituitary adenomas remained extremely low.

Adenoma↗

PubMed1999

Expression of IL-12, IL-10, PGE2, sIL-2R and sIL-6R in seminal plasma of fertile and infertile men.

The involvement of cytokines and other immunoregulatory factors in male infertility is still unclear. In the present study we compared the levels of IL-12, IL-10, PGE2, sIL-2R and sIL-6R in the seminal plasma (SP) of fertile and infertile men. Four groups were included: fertile donors (FERT), infertile men with azoospermia (AZOO), and infertile men with either oligoterato-asthenoazoospermia (OTA), or OTA with genital infection (OTA-INF). Cytokines and cytokine-soluble receptors in semen were evaluated by specific ELISA commercial kits. The levels of IL-12, sIL-2R and sIL-6R were similar in SP of fertile and infertile men. The mean levels of IL-10 in the SP of FERT, OTA and AZOO were 5.6 +/- 0.9, 4 +/- 2.8 and 8 +/- 3.5 pg ml-1, respectively, and did not differ significantly. The mean level of IL-10 in SP from OTA-INF (0.9 +/- 0.5 pg ml-1) was significantly lower than that for FERT (5.6 +/- 1.9 pg ml-1; P = 0.02) and AZOO (8.2 +/- 3.4 pg ml-1; P = 0.05), but not significantly different from that for OTA (3.7 +/- 2.1 pg ml-1). The mean SP level of PGE2 was significantly lower in SP of OTA-INF than FERT (7.67 +/- 2.26 and 19.67 +/- 3.69 micrograms ml-1, respectively; P < 0.02). In conclusion, the seminal plasma from fertile and infertile men contained similar levels of IL-12, sIL-2R and sIL-6R. However, the levels of IL-10 were significantly lower in SP from OTA-INF compared to FERT and AZOO. Our results indicate that specific cytokines and their soluble receptors are involved in the male reproductive system.

Dinoprostone↗

PubMed1999

Mitosis and apoptosis in the pituitary gland: tumour formation or hyperplasia?

Direct analyses of trophic activity in the pituitary have been hampered by the lack of normal human tissue to study and by the short duration of the histologically overt phases of mitosis and apoptosis, which renders significant trophic events difficult to quantify. In rats and dogs, pituitary cell turnover is rapid in youth, declines markedly with age and virtually ceases by 'late middle age'. Specific stimuli superimpose brief but dramatic trophic events on this active background. There is little convincing evidence, as yet, for plasticity, i.e. the persistence of cell population changes after transient stimuli have passed. In contrast to spontaneous pituitary adenomas in rats, human pituitary tumours show relatively modest increases in mitotic activity. In the light of these observations, this chapter examines the accepted models of pituitary adenoma formation and propagation, with special reference to trophic activity, clonality and tumour behaviour.

Adenoma↗

PubMed1999

Psychological and academic functioning in college students with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) has been increasingly recognized as a valid adult diagnosis. Yet the impairments related to ADHD in college students have received little scholarly attention. Psychological and academic impairments in college students not previously diagnosed with ADHD were assessed in a retrospective chart review, using specifically defined diagnostic criteria, and compared with a control group. Students with ADHD had a significantly lower mean grade point average, were more likely to be on academic probation, and reported significantly more academic problems. Measures of psychological impairment in the ADHD group were not significantly different from those in the control group. College students diagnosed with ADHD had a specific pattern of academic impairment. The problems of these students, compared with other groups of children and adults with ADHD, appeared to be more related to a type of learning disorder than to the conceptualization of ADHD in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).

Achievement↗

PubMed1999

Insertion of an amino acid in the DNA-binding domain of the glucocorticoid receptor as a result of alternative splicing.

When the human glucocorticoid receptor (GR) was first sequenced, a predominant form (GRalpha) and a minor variant (GRbeta) were identified. In the present communication, we describe a new variant of the glucocorticoid receptor (GRgamma) in which, as a result of alternative splicing, three bases are retained from the intron separating exons 3 and 4. These three bases code for an additional amino acid (arginine) in the DNA binding domain of the receptor. Insertion of arginine at this site has previously been shown to decrease transcriptional activation by the GR to 48% that of GRalpha. Analysis of cDNA from different tissues shows that the novel form is widely expressed at a relatively high level (between 3.8 and 8.7% of total GR).

Alternative Splicing↗

PubMed1999

Hilbert-space Karhunen-Loève transform with application to image analysis.

A generalization of the Karhunen-Loève (KL) transform to Hilbert spaces is developed. It allows one to find the best low-dimensional approximation of an ensemble of images with respect to a variety of distance functions other than the traditional mean square error (L2 norm). A simple and intuitive characterization of the family of Hilbert norms in finite-dimensional spaces leads to an algorithm for calculating the Hilbert-KL expansion. KL approximations of ensembles of objects and faces optimized with respect to a norm based on the modulation transfer function of the human visual system are compared with the standard L2 approximations.

Algorithms↗

PubMed1999

Apoptotic index as a prognostic factor in Hodgkin's disease.

Hodgkin's disease (HD) is an unusual malignant neoplasm, mainly because of the rarity of tumor cells in the diseased tissues, but also due to a relatively favorable response to treatment. In a previous study, we have shown a variable degree of apoptosis in lymph nodes from HD patients. We now looked for clinicopathological correlations of apoptosis with special emphasis on the prognosis in this disease. A retrospective study of 92 patients was carried out, using in situ end labelling of DNA fragments and an apoptosis detection kit. An apoptotic index (Al) was calculated in each case, as the percentage of apoptotic Hodgkin-Reed-Sternberg cells out of the total number of tumor cells in 10 selected high power fields. An association between a high Al and advanced stages was noted. A Kaplan-Meier analysis showed a negative correlation between Al and survival (p=0.05). In a multivariable analysis adjusting for Ann Arbor stage, a high Al carried a 3.27 fold risk of dying of HD (OR=3.27; Cl=0.89-11.94). However, in our limited cohort of HD patients, Al was not an independent prognostic factor. The results of this study confirm the important role played by apoptosis in HD and suggest that the apoptotic index is probably a negative prognostic marker in this disease. Its assessment in patients with HD may provide a new, important clinical tool.

Adult↗

PubMed1999

Cellular penetration of fluorescently labeled superoxide dismutases of various origins.

BACKGROUND: Using fluorescently labeled superoxide dismutase (SOD) and flow cytometry, we have shown previously that the enzyme CuZn SOD (EC 1.15.1.1) from bovine erythrocytes binds rapidly to the cell surface with slow uptake into the cell during the following hours. The degree of labeling was most important for monocytes in comparison to other blood cells (erythrocytes, lymphocytes, and neutrophils) and fibroblasts. In agreement with the flow-cytometric findings, the inhibition of superoxide production was more important for SOD-pretreated monocytes than for neutrophils, as demonstrated with the cytochrome c reduction assay. It was thus of interest to confirm the observed differences between monocytes and neutrophils with confocal laser microscopy, study in greater detail the kinetics of binding, penetration, and intracellular localization of the enzyme, and compare the results obtained with bovine CuZn SOD with those from SODs of other origins and carrying different active sites. MATERIALS AND METHODS: Recombinant human (rh), bovine, and equine CuZn SODs, as well as rh and E. coli Mn SODs, were studied before use with respect to specific activity and purity (HPLC, SDS-PAGE electrophoresis). Fluorescein isothiocyanate was covalently conjugated to the various SODs for study with high-resolution confocal scanning laser microscopy. Superoxide production by monocytes and neutrophils was measured with the cytochrome c assay. RESULTS: As expected from our experiments with flow cytometry, only rare neutrophils were labeled with FITC-SOD, even with the longest incubation time of 3 hr and the highest dose of 1500 units/ml. In addition, they showed a localized fluorescence pattern that was quite different from the diffuse punctate fluorescence pattern of monocytes. Lymphocytes were not labeled at all. The rapid binding to the cellular surface of monocytes was confirmed, and even after 5 min of preincubation, FITC-SOD was found on a small percentage of monocytes. This was correlated with a reduction in superoxide release after phorbolmyristate acetate (PMA) stimulation by 40%. An interesting finding was the perinuclear accumulation of the penetrated SOD after the longest pretreatment of 3 hr, suggesting a barrier against further progression. Indeed, through confocal microscopy we were able to exclude any fluorescence at the nuclear level. While the fluorescence labeling patterns and the kinetics of penetration were quite similar for bovine, equine, and rh CuZn SOD, the Mn SODs showed poor labeling, correlated with a weak inhibitory effect on cytochrome c reduction, which was not statistically significant. CONCLUSIONS: The rapid binding of native CuZn SODs on the surface of monocytes, leading to reduced superoxide release by these cells, explains the observation that beneficial effects of injected SOD lasted for months despite rapid clearance of the enzyme from the bloodstream, according to pharmacodynamic studies. The preferential binding to monocytes, in contrast to neutrophils, may play a role in chronic inflammatory diseases in which the monocytes are in an activated state. The differences in binding capacity between CuZn SODs and Mn SODs, correlated with different inhibitory effects of superoxide production by monocytes, may also have therapeutic significance.

Animals↗

PubMed1998

Hypovolemia upregulates the expression of neuronal nitric oxide synthase gene in the paraventricular and supraoptic nuclei of rats.

We have examined the effects of isotonic hypovolemia on the expression of the neuronal nitric oxide synthase (nNOS) gene in the paraventricular (PVN) and supraoptic nuclei (SON) of the rat, using in situ hybridization histochemistry with a 35S-labelled oligodeoxynucleotide probe complementary to nNOS mRNA. Intraperitoneal (i.p.) administration of polyethylene glycol (PEG) (MW 4000, 20 ml/kg body weight) dissolved in 0.9% saline (20% w/v) induced isotonic hypovolemia. The expression of the nNOS gene in the PVN and SON 6 h after i.p. administration of PEG was increased significantly in comparison with controls. The dual staining for NADPH diaphorase activity and Fos-like immunoreactivity (Fos-LI) showed that at 3 and 6 h after i.p. administration of PEG, a subpopulation of NADPH diaphorase-positive cells in the PVN and SON exhibited nuclear Fos-LI. These results suggest that NO in the PVN and SON may be involved in the neuroendocrine and autonomic responses to non-osmotic hypovolemia.

Animals↗

PubMed1998

Prolonged severe hypercapnia complicating near fatal asthma in a 35-year-old woman.

OBJECTIVE: We describe a patient with a prolonged and severe hypercapnia occurring during an episode of status asthmaticus induced by ophthalmic instillation of carteolol. SETTING: Prehospital Emergency Medical Service and Pulmonary Intensive Care Unit in a university hospital. PATIENT: A 35-year-old female developed an acute asthma attack while at home, which required advanced life support. INTERVENTION: On hospital admission, arterial blood gases revealed a PaCO2 of 208 mmHg. Hypercapnia persisted with a PaCO2 of more than 190 mmHg for 10 h, with pH always less than 7.00. The patient was finally discharged after 26 days without sequelae. CONCLUSION: This case illustrates the cerebral and cardiovascular tolerance of severe and prolonged hypercapnia associated with major acidosis.

Acidosis, Respiratory↗

PubMed1998

Sub-regional hippocampal vulnerability in various animal models leading to cognitive dysfunction.

Various animal models, involving different brain insults, lead to memory deficits, which can be measured using behavioral tests. In numerous studies, using five different experimental models in rats, we have found that cognitive dysfunction is invariably accompanied by hippocampal CA1 and CA3 pyramidal cells degeneration. However, of these two, the most affected area changes from one model to the other. The present manuscript describes and compares the morphological alterations within the hippocampus in the following experimental models: normal aging, hypoxia, prolonged corticosterone administration, brain ischemia and cholinesterase (ChE) inhibition. In all the above, many hippocampal neurons were severely damaged, however, CA3 pyramidal cells were mostly affected in normal aging and following hypobaric hypoxia, whereas CA1 cells were especially affected following corticosterone administration, global ischemia and ChE inhibition. Several mechanisms, which might be involved in the diverse courses of the lesions are being considered: cerebral oxygen and glucose, glutamate neurotoxicity and calcium involvement. It is anticipated that elucidation of the specific role of CA1 and CA3 hippocampal sub-fields in the various experimental models might help in understanding processes such as age-related neuronal degeneration and assist in their prevention.

Aging↗

PubMed1998

Obstetric outcome of singleton pregnancies conceived by in vitro fertilization and ovulation induction compared with those conceived spontaneously.

OBJECTIVE: To compare the obstetric characteristics of singleton pregnancies conceived by IVF and ovulation induction with those conceived spontaneously. DESIGN: Case-control study. SETTING: Tertiary care medical center. PATIENT(S): All singleton pregnancies that were achieved by IVF (n = 169) and ovulation induction (n = 646) and were delivered from January 1989 through December 1994 were evaluated. Each group was compared with a separate control group that conceived spontaneously (n = 469 and n = 1,902 for the IVF and ovulation induction groups, respectively) and delivered during the same period and was matched in terms of maternal age, gestational age, and parity. INTERVENTION(S): Ovulation induction, IVF-ET. MAIN OUTCOME MEASURE(S): Obstetric complications. RESULT(S): Multivariate analysis showed that patients who conceived by IVF and ovulation induction had a significantly higher risk for gestational diabetes mellitus (odds ratio [OR] = 2.0; 95% confidence interval [CI] = 1.23-3.30 and OR = 1.9, 95% CI = 1.09-1.79, respectively), pregnancy-induced hypertension (OR = 2.1, 95% CI = 1.04-4.10 and OR = 1.5, 95% CI = 1.04-2.02, respectively), and cesarean section (OR = 3.6, 95% CI = 2.44-5.29 and OR = 1.4, 95% CI = 1.09-1.79, respectively) compared with their matched controls. CONCLUSION(S): After controlling for maternal age, gestational age, and parity, we demonstrated that singleton pregnancies conceived by IVF and ovulation induction are at increased risk for maternal gestational diabetes mellitus and pregnancy-induced hypertension, and at greater risk for delivery by cesarean section.

Adult↗

PubMed1998

Spatial memory under acute cold and restraint stress.

This study examined spatial memory as measured by radial arm maze (RAM) performance after exposure to two stress conditions and a normothermic-unrestrained control condition. Male Fischer 344 rats were trained on the win-shift RAM procedure for 7 days, by which time they achieved asymptotic performance. The next day, rats in the two stress groups were exposed to 15 min of restraint in either 37 degrees C water (normothermic-restraint) or in 20 degrees C water (cold-restraint). Rats were then allowed 40 min in a dry cage before being tested in the RAM. Performance was measured using the following dependent variables: number of correct out of the first eight choices, total number of choices, and time per choice. There were statistically significant effects of stress on all these variables; performance decrements were observed in both stress conditions relative to the normothermic-unrestrained condition. Normothermic-restrained rats displayed less impairment than cold-restrained rats on the stress day. Performance of normothermic-restrained rats returned to baseline levels the day after stress, whereas performance for the cold-restrained rats typically did not. This study demonstrates that: 1) restraint and cold stress impair performance on a memory task; and 2) impairment extent is related to stress severity. One of the mechanisms responsible for the observed behavioral deficits under cold stress may involve altered cholinergic function, because we previously demonstrated that hippocampal acetylcholine levels also decrease in relation to the severity of cold stress.

Animals↗

PubMed1998

The effect of some Solanum steroidal alkaloids and glycoalkaloids on larvae of the red flour beetle, Tribolium castaneum, and the tobacco hornworm, Manduca sexta.

Evaluation of the inhibitory effect of a series of secondary plant compounds including steroidal alkaloids and glycoalkaloids on larvae of the red flour beetle, Tribolium castaneum, was investigated. Larval growth was inhibited on artificial diets containing 1 mumol g-1 diet of the glycoalkaloids solamargine, solasonine and tomatine, whereas the corresponding aglycones solasodine and tomatidine, and also tomatidenol, were inactive. The inhibitory effect of solamargine and tomatine, but not of solasonine, was completely abolished by addition of 1 mumol g-1 diet cholesterol and/or sitosterol. Nonetheless, synthetic cholesteryl tomatide displayed significant activity at 2 mumol g-1 diet. Parallel studies with the tobacco hornworm, Manduca sexta, showed marked inhibitory activity of tomatine at a dietary concentration of 1 mumol g-1, whereas the other compounds did not affect sterol metabolism or larval development. An appraisal of the factors influencing the mode of action of the active steroidal glycoalkaloids is attempted.

Alkaloids↗

PubMed1998

Hospitalizations for infectious diseases in Jewish and Bedouin children in southern Israel.

Two different population groups reside in the Negev region of southern Israel and have equal, and free from financial barrier, access to tertiary care at a single regional hospital. The Jewish population has a largely urban and industrialized lifestyle, while the Moslem Bedouins are in transition from their traditional nomadic life to settlement. To examine the differences in morbidity patterns reflected in hospitalizations, the computerized hospitalization records of children <15 years of age, for 1989-1991 were used (n=15,947). Rates of hospitalizations for infectious diseases were significantly higher for Bedouins in comparison to Jews (250 and 121/10,000 child years, respectively, odds ratio (OR): 2.1, 95% confidence interval (CI): 2.0-2.2, p < 0.001). Rates of hospitalization per 10,000 child years in Bedouins and Jews for diarrhea were 114 and 32 (OR: 3.7, 95% CI: 3.3-4.0, p < 0.001), respectively, and for pneumonia 55 and 19 (OR: 2.9, 95% CI: 2.6-3.3, p < 0.001), respectively. In infants the differences were even more pronounced, especially for diarrheal diseases. In Bedouin children infectious diseases were associated with longer hospital stay, more pediatric Intensive Care hospitalizations (OR: 2.7, 95% CI: 1.7-4.5,p < 0.001), and higher in-hospital mortality (OR: 5.7, 95% CI: 2.8-12.2, p < 0.001). Thus, Bedouin children are at higher risks of hospitalizations for infectious diseases in early childhood, as compared to Jewish children. This may reflect the differences in lifestyle, environmental and social conditions of the two populations.

Adolescent↗

PubMed1998

Presence of GHRH mRNA in human pituitary somatotrophinomas and its relationship to in vitro effect of a GHRH-antagonist on GH secretion and cAMP production.

Several earlier studies have shown that some human pituitary GH-secreting somatotrophinomas are able to synthesise and release hypothalamic GHRH and it has been proposed that a positive autocrine feedback loop involving this tumor-derived GHRH may participate in tumorigenesis. We have used in-vitro cell culture and exploited an antagonist to GHRH, (Ac-Tyr1,D-Arg2)-GHRH (1-29)-amide (GHRH-A), to further investigate whether an autocrine loop involving somatotrophinoma-derived GHRH may exist. In situ hybridization demonstrated presence of GHRH transcripts in 5 of 9 human somatotrophinomas. In culture, GHRH-A failed to inhibit basal release of GH or production of cAMP irrespective of presence or absence of GHRH transcripts. However, GHRH-A was able to completely or partially abolish the stimulatory effects of exogenously added GHRH peptide. Additionally, the average stimulatory effect of exogenous GHRH on in vitro GH secretion by somatotrophinomas possessing GHRH mRNA was identical to that shown by tumors not expressing the GHRH gene. Whilst confirming that many human pituitary somatotrophinomas are able to express the GHRH gene, the failure of GHRH-A to inhibit basal GH secretion argues against the concept of the existence of an autocrine stimulatory loop involving secreted GHRH peptide.

Adenoma↗

PubMed1998

Neuronal nitric oxide synthase gene expression in human pituitary tumours: a possible association with somatotroph adenomas and growth hormone-releasing hormone gene expression.

OBJECTIVE: Nitric oxide (NO) has been implicated in the control of the secretory response to growth hormone-releasing hormone (GHRH) and may also modify GH release in response to excitatory aminoacids. Although rat and mouse pituitary cell lines have been shown to express neuronal NO synthase (nNOS), there has until now been no information on nNOS gene expression in human pituitary adenomas. Our objective was to provide such data and correlate the presence of nNOS transcripts with GHRH transcripts. PATIENTS: Pituitary adenoma tissue was obtained from a random selection of 32 patients with somatotrophadenomas, 16 patients with corticotroph adenomas, 39 patients with endocrinologically inactive adenomas and nine patients with macroprolactinomas undergoing transsphenoidal hypophysectomy. MEASUREMENTS: Transcripts for nNOS and GHRH were identified in frozen tissue sections by in situ hybridization histochemistry using synthetic 35S-labelled oligodeoxynucleotide probes with 100% homology to the target transcript. RESULTS: Neuronal NOS transcripts were identified in one of 16 corticotroph adenomas (6%), one of nine macroprolactinomas (11%), six of 39 endocrinologically inactive adenomas (15%) and 13 of 32 somatotroph adenomas (41%). GHRH transcripts were found in a similar distribution to nNOS transcripts in 10 of the 13 nNOS-expressing somatotroph adenomas, and in three of the four remaining adenomas from which suitable tissue was available. Cross-hybridization of the nNOS and GHRH probes to the same target was excluded by including rat brain sections cut through the arcuate nucleus as hybridization controls. Furthermore, two different nNOS oligodeoxynucleotide probes complementary to different regions of the target transcript produced identical results. CONCLUSIONS: These results suggest that there is a close correlation between nNOS gene expression and 'ectopic' expression of GHRH in human pituitary tumours, especially somatotroph adenomas. The relevance of these findings from a functional or pathologenic viewpoint remains unclear, but the data again emphasize that it is not just GH secretion that distinguishes somatotroph adenomas from other pituitary tumours.

Adenoma↗

PubMed1998

Anterior pituitary cell population control: basal cell turnover and the effects of adrenalectomy and dexamethasone treatment.

We have used an extremely accurate, dedicated, real time computerized image analysis system to facilitate the manual quantification of changes in the prevalence of mitotic figures and apoptotic bodies in male rat pituitary following surgical adrenalectomy and, 14 days later, dexamethasone treatment. Under basal conditions, the prevalence of mitotic figures and apoptotic bodies was 0.066+/-0.016% and 0.030+/-0.012% (mean+/-SE) respectively. Dexamethasone treatment reduced the prevalence of mitotic figures and, in adrenalectomized animals, produced a highly significant and reproducible burst of apoptotic activity that peaked 48 h after the beginning of treatment (0.261+/-0.022%) before falling sharply to control levels within a further 8 h. Two weeks after the start of dexamethasone treatment, total pituitary cell numbers continued to decline. The rate of accumulation of mitotic figures in vivo after colchicine treatment indicates that mitosis is histologically overt in 2 microm thick hematoxylin and eosin stained sections under the light microscope for around 80 min; that apoptosis--identified as classical apoptotic bodies--is overt for 44 min and that, on average, a young, adult, male rat anterior pituitary cell either dies or divides as frequently as once every 60-70 days. These data show that transient and apparently trivial fluctuations in the prevalence of apoptotic and mitotic events have a profound effect on pituitary cell population dynamics, and demonstrate that dexamethasone treatment of adrenalectomized rats produces a decline in total anterior pituitary cell numbers that continues for at least 2 weeks after the start of glucocorticoid treatment.

Adrenalectomy↗