Search PubMed⌕ Search

Biomedical subjects

A Levy

Publications and source records attributed to A Levy.

At least 73 records · Page 4Linked to original sources
PubMed2000

Intra-uterine growth retardation results in increased cardiac arrhythmias and raised diastolic blood pressure in adult rats.

OBJECTIVES: Epidemiological evidence in humans suggests that intrauterine growth retardation is associated with an increased risk of hypertension and coronary heart disease in later life. To begin to understand the mechanisms involved, we developed and exploited a rat model of intrauterine growth retardation to assess predisposition to arrhythmias and resting blood pressure levels at defined ages from 4 to 18 months. METHODS: Isolated working heart experiments were carried out on rats that had been subjected to intrauterine growth retardation by prenatal protein deprivation and age-matched male Wistar controls to measure susceptibility to wall stress-induced arrhythmias. In addition, resting systolic and diastolic blood pressures were measured in conscious rats via an indwelling arterial catheter. RESULTS: Hearts from intrauterine growth retarded animals showed significantly more ventricular premature beats and more episodes of ventricular tachycardia at all ages examined (4, 9 and 18 months), and at 4 and 18 months, a reduction in coronary blood flow. Diastolic pressure was significantly raised by intrauterine growth retardation in both groups examined (4 and 9 months). CONCLUSIONS: Protein malnutrition during the intrauterine period results in profound intrauterine growth retardation that is associated with a raised diastolic blood pressure and an increased predisposition to cardiac arrhythmias in later life. These results are consistent with epidemiological observations made in human populations, and as similar pathophysiological changes may operate in both situations, intrauterine protein deprivation may be a useful model to help define some of the mechanisms involved.

Analysis of Variance↗
PubMed2000

Production of interleukin-1-like molecules by human sperm cells.

OBJECTIVE: To characterize and localize interleukin (IL)-1alpha and IL-1beta in human sperm cells. DESIGN: Prospective and comparative study. SETTING: Andrology clinic of a university hospital. PATIENT(S): Two groups of normogonadotropic men: 17 fertile men (donors with proved fertility) and 8 oligoteratoasthenospermic infertile men. INTERVENTION(S): None. MAIN OTUCOME MEASURE(s): Evaluation of IL-1alpha and IL-1beta levels and expression in sperm cells by immunohistochemical staining, immunoassay, and Western blot analysis. RESULT(S): Both types of IL-1-like molecules (IL-1alpha and IL-1beta) were expressed in the tail, neck, and head of sperm cells of fertile men and patients with oligoteratoasthenospermia. Swim-up sperm cells from fertile men and patients with oligoteratoasthenospermia secreted similar levels of IL-1-like molecules. The levels of IL-1beta-like molecules were higher than those of IL-1alpha-like molecules in both groups. The expressed IL-1-like molecules were characterized by the presence a 60-kd protein for both IL-1alpha-like and IL-1beta-like molecules. In some samples of both fertile men and infertile men with oligoteratoasthenospermia, 17-kd, 33-kd, and 45-kd IL-1beta-like molecules were detected. Impairment of sperm function, such as decreased sperm count and motility and/or impaired morphology, was not related to the capacity of sperm cells to produce IL-1-like molecules. CONCLUSION(S): IL-1 molecules originating in sperm cells may play a role in the physiologic functions of sperm cells (autocrine effect) and/or in cell-cell interactions within the testis (paracrine effect).

Blotting, Western↗
PubMed2000

Non-surgical management of erectile dysfunction.

Erectile dysfunction is a common and distressing medical condition that is now highly amenable to treatment almost irrespective of the cause. Safe, non-surgical treatments with unequivocal efficacy are psychological therapy, intracorporeal injection of vasoactive drugs, transurethral vasodilators and oral sildenafil, all of which have been reported to have a 50-70% overall response rate. Vacuum constriction devices are acceptable for some, usually older patients and oral yohimbine is thought to have marginal efficacy. Local creams to induce or enhance erectile function are currently being investigated. There is no place for androgen supplementation unless the patient is profoundly hypogonadal. Treatment of hyperprolactinaemia is very effective but is a rare cause of erectile dysfunction. As intercourse may entail an unfamiliar level of physical activity, it is sensible to ensure that the patient is able to climb a flight or two of stairs comfortably without provoking undue breathlessness or chest pain and to provide suitable advice about technique before commencing treatment. Once it is clear to the patients that erectile dysfunction can be satisfactorily overcome, the long-term use of treatments to do so tends to wane. Thus, although the prospect of effective treatment for what had been for many a distressing life sentence has the potential to place new demands on the health service, there is no evidence that restrictions on prescribing will prove economically rational.

Administration, Topical↗
PubMed2000

The influence of gonadal steroids on pre-pro melanin-concentrating hormone mRNA in female rats.

Melanin-concentrating hormone (MCH) may have a regulatory role in the control of luteinizing hormone (LH) release. We have investigated if gonadal steroids induce changes in the expression of pre-pro MCH (ppMCH) that are associated with changes in the pattern of LH release. Using quantitative in-situ hybridization histochemistry we have determined the effect of administration of either oestradiol benzoate (5 microg/rat) or oestradiol benzoate followed 44 or 48 h later by progesterone (0.5 mg/rat) to ovariectomized rats on the expression of ppMCH in the medial and lateral zona incerta and the lateral hypothalamus. The prevalence of ppMCH transcripts in the intact female rat at 12.00 and 19.00 h on proestrus and the first day of dioestrus was also examined. Oestrogen reduced the intensity of hybridization signal for ppMCH mRNA and this was associated with both a decrease in the number of cells in which the message was detected in the medial zona incerta and a negative feedback effect on LH release in ovariectomized rats. Progesterone administration to oestradiol benzoate-primed rats did not alter the reduced expression in the medial zona incerta in spite of its positive feedback effect on LH release. We suggest that progesterone may act only on post-translational events. Expression in the MCH cell bodies of the lateral zona incerta were not affected but there was a transient decrease 4 h after progesterone treatment in the oestradiol benzoate-primed rats in expression in the lateral hypothalamus. No changes in ppMCH mRNA were seen in intact animals on proestrus or the first day of dioestrus indicating that gonadal steroids are not important in the modulation of ppMCH gene expression during the oestrous cycle. In other steroid-dependent physiological situations, however, oestrogen may influence the expression of ppMCH in a subpopulation of cell bodies in the medial zona incerta.

Animals↗
PubMed2000

The effects of acute and chronic stresses on vasotocin gene transcripts in the brain of the rainbow trout (Oncorhynchus mykiss).

Secretion of adrenocorticotropic hormone (ACTH) from the fish pituitary, which occurs in times of stress, is stimulated by several hypothalamic neuropeptides, one of which is arginine vasotocin (AVT). This study investigates whether gene expression for AVT is up-regulated during acute or chronic stress. Rainbow trout (Oncorhynchus mykiss) were subjected to one of two forms of acute stress-either 2 h confinement followed by 2 h recovery, or capture and transfer to low water for 2 min followed by 4 h recovery in their home tank before autopsy. In other experiments, these stresses were repeated daily for 5 or 6 days (chronic stress). Quantification of AVT transcript prevalence in the parvocellular and magnocellular neurones of the preoptic nucleus after in situ hybridization was used as a monitor of the AVT gene response to stress. The results showed that acute confinement, but apparently not brief low-water stress, significantly increased AVT transcript prevalence in a group of parvocellular perikarya. When applied repeatedly, both forms of stress caused habituation, such that the AVT hybridization signal remained at control or even lower levels despite elevated pro-opiomelanocortin transcripts in the corticotropes and raised plasma cortisol concentrations. The AVT hybridization signal in the magnocellular perikarya showed no significant response to either acute or chronic stress. The results support the idea that these parvocellular AVT neurones are involved in ACTH stimulation during acute stress, and that the system habituates to chronic stresses.

Animals↗
PubMed2000

Chronic iodine deprivation attenuates stress-induced and diurnal variation in corticosterone secretion in female Wistar rats.

Many millions of people throughout the world are at risk of developing iodine deficiency-associated disorders. The underlying effects of iodine deficiency on neuroendocrine function are poorly defined. We have studied stress-induced and diurnal variation in corticosterone secretion in female rats rendered chronically hypothyroid by feeding them an iodine-free diet for 6 months. Corticosterone secretory responses in iodine deficient animals were compared to those seen in animals rendered hypothyroid with propylthiouracil and untreated controls. By using a well-validated, automated blood sampling system to collect small samples of blood over the complete daily cycle in unrestrained animals, we have demonstrated for the first time that the normal diurnal rhythm of corticosterone secretion is lost in chronic iodine deficiency and that the corticosterone secretory response to the psychological stress of 10 min exposure to white noise is attenuated. Despite restoration of circulating triiodothyronine and thyrotropin releasing hormone- and thyroid stimulating hormone beta-transcript prevalence in the hypothalamus and pituitary, respectively, 1 month after restoration of normal iodine-containing diet both the diurnal variation in corticosterone levels and the corticosterone secretory response to the noise stress remained reduced in amplitude compared to control animals. Thus, chronic hypothyroidism induced by iodine deficiency significantly attenuates hypothalamo-pituitary-adrenal axis activity, an effect that persists after functional recovery of the thyroid axis.

Acoustic Stimulation↗
PubMed2000

Changes in contractile protein gene expression with ageing and with captopril-induced regression of hypertrophy in the spontaneously hypertensive rats.

BACKGROUND: Left ventricular hypertrophy (LVH) is present in young spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto (WKY) rats and treatment of SHR with captopril leads to regression of LVH. Hypertrophy produces changes in gene expression for myofibrillar proteins with increased ratios of skeletal to cardiac actin and beta to alpha-myosin heavy chain (MHC). OBJECTIVES: The objective of this study was to follow changes in transcript prevalence for these four proteins during ageing and with captopril treatment in SHR and WKY rats. METHODS: Untreated SHR and WKY rats were studied at 100, 156, 350 and 450 days. Groups at 100 and 350 days were divided into a treatment group (given captopril) and untreated controls. Transcripts were measured using in situ hybridization. RESULTS: Both cardiac and skeletal actin were increased in untreated SHR compared to WKY rats (P<0.01 and P<0.05, respectively). alpha-MHC was increased (P<0.01) whilst beta-MHC was normal in 100-day-old SHR (an age when LVH was present) compared with WKY rats. With ageing, alpha-MHC declined and beta-MHC increased giving the increased ratio of beta to alpha-MHC transcripts reported by other investigators. Treatment of SHR led to a significant decline in skeletal actin transcripts (P< 0.01) and reversed the rise in beta-MHC expression that occurred with ageing (P< 0.01). CONCLUSIONS: LVH in SHR is associated with increased skeletal and cardiac actin transcripts. Despite unequivocal LVH in SHR at 100 days of age, alpha rather than beta-MHC transcripts were increased. Only with ageing did the classically reported increased ratio of beta to alpha-MHC transcripts become apparent Captopril treatment reduced skeletal actin transcripts and reversed the increase in beta-MHC that occurred with ageing.

Actins↗
PubMed2000

Involvement of serum and lipopolysaccharide in the production of interleukin-1- and interleukin-6-like molecules by human sperm cells.

PROBLEM: To examine the capacity of sperm cells from fertile and infertile men to secrete interleukin (IL)-6, and the involvement of serum factors and lipopolysaccharide (LPS) in the regulation of IL-6 and IL-1 production by sperm cells. METHODS: Swim-up sperm cells from fertile (donors) and oligoteratoasthenospermic (OTA)-infertile men were incubated with or without 5% fetal calf serum (FCS) and LPS (10 microg/mL) for 2-24 hr. After incubation, IL-6 and IL-1 bioactivities were measured in supernatants and lysates by specific bioassays (B9 cell proliferation assay and 1A-5 system, respectively). RESULTS: IL-6- and IL-1-like activities were observed to be produced by swim-up sperm cells from both study groups. Stimulation of swim-up sperm cells with either LPS or FCS or both together did not affect their capacity to produce IL-1. However, LPS, but not serum increased the secretion levels of IL-6 by swim-up sperm cells. CONCLUSIONS: Swim-up sperm cells from both study groups constitutively produce IL-6 and IL-1, and serum components did not affect this capacity. However, LPS was shown to increase the capacity of swim-up sperm cells of both study groups to secrete IL-6, but not IL-1. Cytokines may be involved in the physiology and pathophysiology of sperm functions and, thus, may affect male fertility.

Animals↗
PubMed2000

Differential expression of sialyl and non-sialyl-CD15 antigens on Hodgkin-Reed-Sternberg cells: significance in Hodgkin's disease.

CD15 expression has been used for years to confirm the diagnosis of Hodgkin's disease (HD). Little is, however, known on the relevance of the CD15 antigen to the pathobiology of the disease and there is conflicting evidence as to the prognostic value of its expression. To investigate the significance of the differential expression of CD15 in Hodgkin's disease, a retrospective study of 102 patients with "classical" Hodgkin's disease was performed. Immunohistochemical studies were carried out using antibodies against two types of CD15: non-sialylated CD15 (LeuM1 and 80H5) and sialylated CD15 (FH6 and CSLEX1). Cases that were negative for non-sialylated CD15 or positive for the sialylated variant were stained again following neuraminidase pretreatment. The cohort included 27 patients in whom sequential biopsies were available. Both CD15 expression in its non-sialylated form and absence of sialyl-CD15 expression correlate with a favorable outcome. Subsequent biopsies show a preferential expression of sialyl-CD15, notably in bone marrow metastases. Our findings suggest that, in the progression of HD towards a widely disseminated disease, the LewisX moiety of the CD15 antigen on the tumor cells acquires a sialyl-group. This change may confer on the tumor cells the capacity to metastasize.

Actuarial Analysis↗
PubMed2000

Hodgkin's lymphoma in the Bedouin of southern Israel: epidemiological and clinical features.

BACKGROUND: A previous study on Hodgkin's lymphoma in southern Israel found that Bedouin patients had an increased rate of Epstein-Barr virus expression in their tumor cells. OBJECTIVES: To determine the influence of the patients' communities on the pattern of disease in HL. METHODS: We compared the clinical features, demographic data, stage at diagnosis, treatment modality and outcome, as well as laboratory findings, in four community-based subgroups. These groups comprised kibbutz residents (n = 11), Bedouin (n = 19), new immigrants from the former USSR (n = 22), and town-dwellers (n = 82). RESULTS: The Bedouin patients differed significantly from the new immigrants and town-dwellers, particularly regarding the rate of EBV sequences in the tumor tissues, and a poorer response to treatment. The kibbutz patients did not differ significantly from the other populations regarding most of the parameters studied, but showed an intermediate expression of EBV antigens compared to Bedouin patients and the rest of the cohort. CONCLUSIONS: This study indicates that HL may behave differently in different population groups in a given geographic area. Notably, the Bedouin patients showed markedly different clinical and biological patterns of this malignancy.

Adolescent↗
PubMed1999

Distribution of tracer levels of cocaine in the human brain as assessed with averaged [11C]cocaine images.

The Ability of cocaine to block the dopamine transporter (DAT) in the nucleus accumbens, as well as its non-striatal and non-DAT actions, appears to be crucial for its reinforcing/rewardig effects. However, we have been unable to use PET and [11C]cocaine to map small regions with greater sensitivity due in part to the low specific to non-specific binding ration of [11C]cocaine. In order to increase the signal to noise ratio of the individual [11]cocaine images, we averaged the distribution volume (DV) PET images of 17 normal controls. In addition we also obtained averaged images for the dynamic set (14 time frames) and for the K1 values. The dynamic images were used to generate the average time activity curves from which we obtained the time required to half maximum clearance (T50). Twenty-nine ROIs were identified in the Talarach-Tournoux atlas and were then projected to the corregistered average PET image. The brain regions clustered in 3 groups according to their DV values. The highest activity (Group DV.1, 4.6-3.7) included putamen > accumbens > caudate. Intermediate DVs (Group DV.2, 3.2-2.8) included thalamus (mediodorsal and ventrolateral nucleus) > precuneus and posterior cingulate gyrus > amygdala, hippocampus, and temporal pole. Group DV.3 with low DVs (2.6-2.1) included the orbital cortex, precentral gyrus, and cerebellum. The brain regions clustered in 3 groups according to their T50 values. Regions with the faster clearance rates (15-20 minutes) included the orbital cortex, posterior cingulate, dorsomedial thalamus, precuneus, and cerebellum. Intermediate clearance rates (20-25 minutes) included caudate, putamen and accumbens regions with the slowest clearance rates (25-30 minuters) included caudate, putamen, and accumbens. In addition to the previously documented high binding of cocaine in striatum and moderate binding in thalamus in the living human brain this study also documents binding of cocaine in limbic and paralimbic brain regions. Further work is required to characterize the binding properties of cocaine in these brain areas and to elucidate their role in the reinforcing and addictive properties of cocaine.

Adult↗
PubMed1999

High-density screen of human tumor cell lines for homozygous deletions of loci on chromosome arm 8p.

Tumor cell-specific homozygous deletions coinciding at a particular genetic location may indicate the inactivation of a nearby tumor suppressor gene. Forty-six human cancer cell lines of prostate, pancreatic, lung, liver, and colon origin were screened for homozygous deletions of 139 expressed sequence tag (EST) and sequence-tagged site (STS) loci spanning the entire short arm of chromosome 8. Only one Southern blot-verified homozygous deletion was detected in this set of cell lines. The deletion, in pancreatic tumor cell line MIA-PaCa-2, encompassed two screening loci, D8S549 and D8S1992, and overlapped another previously described homozygous deletion of band 8p22 in a metastatic prostate cancer specimen. Both deletions entirely removed the candidate tumor suppressor gene N33. These data define a consensus homozygous deletion region in chromosome band 8p22.

Chromosome Deletion↗
PubMed1999

Pelvic resection of recurrent rectal cancer: technical considerations and outcomes.

PURPOSE: Pelvic recurrence of rectal cancer is an ominous event for the patient and a formidable challenge to the managing surgeon. We reviewed the results of abdominosacral resection to manage these patients and correlated outcome (survival and recurrence) with known prognostic factors. METHODS: An abdominosacral resection was performed on 61 patients with pelvic recurrence (53 with curative intent and 6 for palliation; 2 had extended pelvic resection). Of the 53 patients (32 males; average age, 59 years) previous resection included abdominoperineal resection in 27 patients, abdominoperineal resection plus hepatic lobectomy in 2 patients, low anterior resection in 19 patients, plus trisegmentectomy in 1 patient, and advanced primary cancers in 4 patients. Initial primary stage was Dukes B (64 percent) and Dukes C (36 percent). All had been irradiated (3,000-6,500 in 50 patients, 8,300 and 11,000 in 2 patients, and unknown dose in 3 patients). Preoperative carcinoembryonic antigen was elevated (>5 ng/ml) in 54 percent. Extent of resection: high sacral resection S-1-S2 was done in 32 patients, midsacrum in 14 patients, and low S-4-S-5 in 6 patients. Twenty-eight patients (60 percent) required partial or complete bladder resection with or without adjacent viscera, and all had internal iliac and obturator node dissection. RESULTS: There were four postoperative (within 60 days) deaths, 8 percent in curative groups (5.4 percent overall). Major complications included prolonged intubation (20 percent), sepsis (34 percent), posterior wound infection or flap separation (38 percent). The survival rate in the curative group (49 postoperative survivors) was 31 percent at five years, with 13 patients surviving beyond five years. Seven of these patients survived from 5 to 21 years, whereas six patients recurred again and died within 5.5 to 7.5 years after abdominosacral resection. Disease-free survival rate at five years was 23 percent. Recent reconstruction with large composite myocutaneous gluteal flaps in 5 patients permitted complete sacral wound coverage, resulting in earlier ambulation and reduced hospital stay. CONCLUSIONS: Abdominosacral resection permits removal of pelvic recurrence of rectal cancer that is fixed to the sacrum and is associated with long-term survival in 31 percent of patients. Recent technical advances have improved the short-term outcome and have made the procedure more feasible for surgical teams familiar with these techniques.

Abdomen↗
PubMed1999

A role for the homeobox gene Xvex-1 as part of the BMP-4 ventral signaling pathway.

BMP-4 is believed to play a central role in the patterning of the mesoderm by providing a strong ventral signal. As part of this ventral patterning signal, BMP-4 has to activate a number of transcription factors to fulfill this role. Among the transcription factors regulated by BMP-4 are the Xvent and the GATA genes. A novel homeobox gene has been isolated termed Xvex-1 which represents a new class of homeobox genes. Transcription of Xvex-1 initiates soon after the midblastula transition. Xvex-1 transcripts undergo spatial restriction from the onset of gastrulation to the ventral marginal zone, and the transcripts will remain in this localization including at the tailbud stage in the proctodeum. Expression of Xvex-1 during gastrula stages requires normal BMP-4 activity as evidenced from the injection of BMP-4, Smad1, Smad5 and Smad6 mRNA and antisense BMP-4 RNA. Xvex-1 overexpression ventralizes the Xenopus embryo in a dose dependent manner. Partial loss of Xvex-1 activity induced by antisense RNA injection results in the dorsalization of embryos and the induction of secondary axis formation. Xvex-1 can rescue the effects of overexpressing the dominant negative BMP receptor. These results place Xvex-1 downstream of BMP-4 during gastrulation and suggest that it represents a novel homeobox family in Xenopus which is part of the ventral signaling pathway.

Amino Acid Sequence↗
PubMed1999

Kinetics of brain cholinesterase inhibition following metrifonate administration.

In previous metrifonate (MTF) studies, there has been evidence for a preferential functional effect of the drug in cortical but not in striatal regions. In the present study we investigated the kinetics of brain cholinesterase (ChE) inhibition following an acute administration of MTF (100 mg/kg) in various brain regions of young and old Fischer 344 rats. The main objective was to test the hypothesis that the functional regional selectivity, observed in previous studies, was correlated with the extent of ChE inhibition. Using Karnovsky's method for histochemical staining, the highest staining intensity in control rats was found in the striatum and hippocampus, compared to a low basal activity in the frontal and frontoparietal cortices. In the striatum of drug treated old rats, enzyme inhibition was somewhat greater than that found in young rats. However, in the hippocampus, four to eight hours following MTF administration, the inhibition was greater in young compared to old rats. The differences in the sensitivity of various brain regions towards MTF induced ChE inhibition could not be correlated with the regional variation of MTF functional effects.

Animals↗