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J M Weiss

Publications and source records attributed to J M Weiss.

At least 19 recordsLinked to original sources
PubMed2006

Rapid and efficient nonviral gene delivery of CD154 to primary chronic lymphocytic leukemia cells.

Interactions between CD40 and CD40 ligand (CD154) are essential in the regulation of both humoral and cellular immune responses. Forced expression of human CD154 in B chronic lymphocytic leukemia (B-CLL) cells can upregulate costimulatory and adhesion molecules and restore antigen-presenting capacity. Unfortunately, B-CLL cells are resistant to direct gene manipulation with most currently available gene transfer systems. In this report, we describe the use of a nonviral, clinical-grade, electroporation-based gene delivery system and a standard plasmid carrying CD154 cDNA, which achieved efficient (64+/-15%) and rapid (within 3 h) transfection of primary B-CLL cells. Consistent results were obtained from multiple human donors. Transfection of CD154 was functional in that it led to upregulated expression of CD80, CD86, ICAM-I and MHC class II (HLA-DR) on the B-CLL cells and induction of allogeneic immune responses in MLR assays. Furthermore, sustained transgene expression was demonstrated in long-term cryopreserved transfected cells. This simple and rapid gene delivery technology has been validated under the current Good Manufacturing Practice conditions, and multiple doses of CD154-expressing cells were prepared for CLL patients from one DNA transfection. Vaccination strategies using autologous tumor cells manipulated ex vivo for patients with B-CLL and perhaps with other hematopoietic malignancies could be practically implemented using this rapid and efficient nonviral gene delivery system.

CD40 Ligand↗
PubMed2006

Regulation of GnRH I receptor gene expression by the GnRH agonist triptorelin, estradiol, and progesterone in the gonadotroph-derived cell line alphaT3-1.

The secretion of luteinizing hormone (LH) and the GnRH receptor (GnRH-R) concentration are modulated by ovarian steroids and GnRH. To elucidate whether this regulation is due to alterations at the transcriptional level, we examined the GnRH I-R mRNA expression in the gonadotroph-derived cell line alphaT3-1 treated with different estradiol and progesterone paradigms and the GnRH I agonist triptorelin. alphaT3-1 cells were treated with different steroid paradigms: 1 nM estradiol or 100 nM progesterone for 48 h alone or in combination. Cells were exposed to 10 nM or 100 pM triptorelin for 30 min, 3 h, 9 h, or, in pulsatile way, with a 5-min pulse per hour. The GnRH I-R mRNA was determined by Northern blot analysis. GnRH I-R mRNA from cells treated with continuous triptorelin decreased in a time- and concentration-dependent manner. Pulsatile triptorelin increased GnRH I-R gene expression. Progesterone alone further enhanced this effect, whereas estradiol and its combination with progesterone diminished it. Continuous combined treatment with estradiol and progesterone lead to a significant decrease of GnRH I-R mRNA by 30% and by 35% for estradiol alone. The addition of 10 nM triptorelin for 30 min or 3 h could not influence that steroid effect. In conclusion, estradiol and progesterone exclusively decreased GnRH I-R mRNA in alphaT3-1 cells no matter whether they are treated additionally with the GnRH I agonist triptorelin. The enhanced sensitivity of gonadotrophs and GnRH I-R upregulation by estradiol is not due to increased GnRH I gene expression because GnRH I-R mRNA is downregulated by estradiol and progesterone. Other pathways of the GnRH I-R signal transduction might be involved.

Animals↗
PubMed2005

Polymorphic variation in hOGG1 and risk of cancer: a review of the functional and epidemiologic literature.

The gene encoding human 8-oxoguanine glycosylase 1 (hOGG1) is involved in DNA base excision repair. The encoded DNA glycosylase excises 7,8-dihydro-8-oxoguanine (8-OHdG), a highly mutagenic base produced in DNA as a result of exposure to reactive oxygen species (ROS). Polymorphisms in this gene may alter glycosylase function and an individual's ability to repair damaged DNA, possibly resulting in genetic instability that can foster carcinogenesis. In order to elucidate the possible impact of polymorphisms in hOGG1, we performed a literature review of both functional and epidemiologic studies that assessed the effects of these polymorphisms on repair function, levels of oxidative DNA damage, or associations with cancer risk. Fourteen functional studies and 19 epidemiologic studies of breast, colon, esophageal, head and neck, lung, nasopharyngeal, orolaryngeal, prostate, squamous cell carcinoma of the head and neck (SCCHN), and stomach cancers were identified. Although the larger functional studies suggest reduced repair function with variant alleles in hOGG1, the evidence is generally inconclusive. There is some epidemiologic evidence that risk for esophageal, lung, nasopharyngeal, orolaryngeal, and prostate is related to hOGG1 genotype, whereas risk of breast cancer does not appear related. In studies that explored potential interactions with environmental factors, cancer risk for hOGG1 genotypes differed depending on exposure, especially for colon cancer. In summary, there is limited evidence that polymorphisms in hOGG1 affect repair function and carcinogenesis. Larger, well-designed functional and epidemiologic studies are needed to clarify these relationships, especially with respect to interactions with other DNA repair enzymes and interactions with environmental factors that increase carcinogenic load.

DNA Glycosylases↗
PubMed2005

The subdiaphragmatic vagus nerves mediate activation of locus coeruleus neurons by peripherally administered microbial substances.

Our earlier studies demonstrated that representative microbial substances--lipopolysaccharide, peptidoglycan, and poly-inosine: poly-cytosine (poly(I):(C))--increased the spontaneous discharge rates and sensory-evoked responses of isolated locus coeruleus (LC) neurons in a dose- and time-related manner after i.p. injection into rats. We then turned our attention to the mechanism by which microbial substances administered into the peritoneal cavity affect the LC neurons. The involvement of the subdiaphragmatic vagus nerves was examined in this regard since several brain responses to peripherally administered lipopolysaccharide have been found to depend upon the integrity of these nerves. The experiments reported here show that lipopolysaccharide, peptidoglycan, and poly(I):(C) all failed to excite LC neurons after i.p. injection into rats that had previously been subjected to complete transection of the subdiaphragmatic vagus nerves. Furthermore, selective transection of the subdiaphragmatic vagus nerve trunks indicated that the dorsal trunk, and not the ventral trunk, was necessary to excite LC neurons in response to i.p. lipopolysaccharide. The inability of LC neurons to respond to i.p. lipopolysaccharide in vagotomized rats is unlikely to be attributed to a desensitization of the neurons to lipopolysaccharide since i.c.v. injection of lipopolysaccharide excited LC neurons in vagotomized rats as it did in vagus-intact rats. These findings suggest that a variety of microbial substances excited LC neurons after administration into the peritoneal cavity in a manner involving the subdiaphragmatic vagus nerves.

Animals↗
PubMed2003

Effects of insulin on luteinizing hormone and prolactin secretion and calcium signaling in female rat pituitary cells.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and hyperinsulinemia, which might contribute to the hypersecretion of luteinizing hormone (LH). Hyperprolactinemia is another finding in a subgroup of patients with PCOS, whereas its relation to hyperinsulinemia is not fully understood yet. METHODS: In the present study we tested the hypothesis that insulin might affect LH or prolactin secretion of cultured female rat pituitary cells. To address the mechanisms by which insulin could act at the intracellular level we examined the GnRH- and TRH-induced Ca(2+) signals in single gonadotrophs and lactotrophs, because Ca(2+) is an important component of GnRH signal transduction that is closely related to exocytosis. RESULTS: Cells treated for 24 h with insulin (10(-9) M) showed an enhancement of basal and agonist-induced LH and prolactin secretion. Insulin did not affect GnRH- and TRH-induced Ca(2+) signals compared to controls. There were no differences neither in the frequency nor in the amplitude of the Ca signal. CONCLUSION: Our findings suggest that insulin might contribute to LH hypersecretion. Insulin might be partially responsible for hyperprolactinemia. Since insulin did not affect Ca signaling, other components of the GnRH signal transduction pathway might be involved in LH hypersecretion.

Animals↗
PubMed2003

[Allergic contact dermatitis to common ivy (Hedera helix L.)].

Common ivy (Hedera helix L.) is a ubiquitous plant in Europe whose major allergen falcarinol has moderate allergic potential. It is not related to poison ivy (Toxicodendron spp.). There are no cross reactions between the allergens of common ivy (falcarinol) and poison ivy (urushiol). Contact with common ivy or falcarinol may lead to sensitization and then a delayed hypersensitivity reaction. There are only few cases described in the literature. We report on a male hobby gardener with appropriate clinical history and positive patch test. The pathogenic mechanism is a type IV reaction following a sensitization exposure. Gardeners and landscape architects with frequent exposure to common ivy and thus a high risk of sensitization should wear appropriate protective clothing.

Adult↗
PubMed2003

[The use of oral antidiabetic drugs in the treatment of polycystic ovary syndrome].

The polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. It is a complex metabolic-endocrine disorder with severe long-term health consequences like type 2 diabetes. The increased risk for cardiovascular diseases in women with PCOS is due to diabetes, adipositas and dyslipidemia. Insulin resistance plays a key role in the pathophysiology of this syndrome. This makes the use of oral antidiabetic drugs most compelling. The majority of studies have shown amelioration of the typical symptoms like hyperandrogenism and cycle irregularities. Ovulation and pregnancy rates increased. Furthermore these drugs might be cardioprotective by improving insulin sensitivity and reduce the risk for type 2 diabetes. This article reviews the use of different oral antidiabetic drugs in the treatment of PCOS and their influence on fertility, the risk for type 2 diabetes and cardiovascular diseases.

Acarbose↗
PubMed2003

Interactions of insulin-like growth factors and estradiol in rat pituitary gonadotrophs.

Insulin-like growth factors are involved in the regulation of gonadotropin secretion. Insulin-like growth factor I (IGF-I) has an augmenting effect on gonodotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) release from female rat gonadotrophs that is facilitated by estradiol. To identify the underlying mechanisms, we investigated whether IGF-I influences total LH pool and the production of intracellular inositol phosphate. In another series of experiments we tested whether IGF-II and estradiol affect LH release of gonadotrophs. Pituitary cells were incubated with 100 pM IGF-I and/or 100 pM estradiol for 24 h. They were stimulated, partially in the presence of Wortmannin, an inhibitor of phosphoinositide 3-kinase, with 330 pM GnRH for 3 h. Subsequently, total LH pool (released and remaining hormone content in lysed cells) in cultures was measured. Intracellular inositol trisphosphate of alphaT3-1 cells, a gonadotrope cell line, treated with estradiol and IGF-I as described before and stimulated with 100 nM GnRH for 15 min was analyzed by ion exchange chromatography. To determine the interaction of IGF-II and estradiol on GnRH-stimulated LH secretion, cells were treated with increasing concentrations of IGF-II (0.05 pM-10 nM) and 100 pM estradiol. IGF-I significantly increased the accumulation of inositol trisphosphate in basal and GnRH-stimulated cells. IGF-I, estradiol, or their combinations did not change total LH pool, although they enhanced LH secretion. Wortmannin abolished the positive effects of IGF-I and estradiol on LH secretion. IGF-II alone increased basal, but not GnRH-induced LH secretion at low concentrations (0.05 pM). Additional estradiol treatment further increased basal, but not GnRH-induced LH secretion. In conclusion, our results suggest that increased LH secretion from female anterior pituitary cells after IGF treatment is due to the amplification of early signal transduction steps rather than changes in LH pool. The inositol trisphosphate signaling pathway is involved in the regulation of LH secretion from gonadotrophs treated with IGF-I. It is not likely that IGF-II plays an important role in the regulation of gonadotropin secretion.

Animals↗
PubMed2003

Actions of GnRH antagonists on IGF-II, IGF-binding protein-2 and pregnancy-associated plasma protein-A in human granulosa-lutein cells.

OBJECTIVE: Recently, GnRH antagonists (GnRHants) have been introduced for the prevention of premature LH surges during controlled ovarian hyperstimulation (COH). Here we investigated whether the GnRHants cetrorelix and ganirelix exert effects on the human ovarian IGF system. Since controversy exists on the action of GnRH agonists in the human ovary, we also tested the effect of triptorelin on IGF-II, IGF-binding protein-2 (IGFBP-2) and pregnancy-associated plasma protein-A (PAPP-A) in cultured human granulosa-lutein cells. DESIGN: In vitro cell culture study in a research laboratory of a university hospital. PATIENTS: Cells were obtained from patients treated with different protocols of COH. In addition to gonadotropins they received triptorelin or cetrorelix. Cells were treated with triptorelin, cetrorelix or ganirelix, 1 nmol/l each, for 48 h. IGF-II, IGFBP-2 and PAPP-A were measured by RIA and enzyme immunoassay respectively. RESULTS: GnRHants and triptorelin did not affect IGF-II, IGFBP-2 or PAPP-A. CONCLUSIONS: We conclude that GnRHants do not exert any significant effects on the IGF system of granulosa-lutein cells and therefore their introduction into protocols of COH is unlikely to impair ovarian function.

Cells, Cultured↗
PubMed2002

Preparation of cycles for cryopreservation transfers using estradiol patches and Crinone 8% vaginal gel is effective and does not need any monitoring.

Supernumary pronucleated stage oocytes (PN) can be cryopreserved and later transferred in spontaneous, stimulated or artificial cycles. In this study, we re-evaluated 342 artificial cycles with a transdermal estradiol release system (Estraderm TTS 100) in combination with a vaginal progesterone delivery system (Crinone 8%). Endometrial thickness and serum estradiol on day 14 were correlated with clinical and ongoing pregnancy rates. Endometrial thickness between 7 and 15 mm did not relate to significantly different pregnancy rates. The estradiol serum level did not predict success. In conclusion, this method of endometrial preparation is comfortable for patients and monitoring is unnecessary.

Administration, Cutaneous↗
PubMed2002

Luteal phase support using either Crinone 8% or Utrogest: results of a prospective, randomized study.

The Crinone 8% preparation makes it possible to administer natural progesterone (90 mg) vaginally once daily for luteal phase support (LPS). Until now, no prospective, randomized studies have directly compared this new preparation with widely used Utrogest capsules, which were originally designed for oral administration but are used routinely as a vaginal preparation. A prospective, randomized study investigated 126 patients undergoing cycles of in vitro fertilization (IVF) and IVF/intracytoplasmic sperm injection (ICSI). Patients received either Crinone 8% (n = 73) vaginally once daily or two Utrogest capsules (n=53) vaginally three times daily (600 mg). Clinical pregnancy rates were comparable (28.8 versus 18.9%), as were clinical abortion rates until 12 weeks of gestation (14.3 versus 10.0%) and clinical ongoing pregnancy rates (24.7 versus 17.0%) in the Crinone 8% and Utrogest groups, respectively. Forty-seven non-pregnant patients were randomly selected to answer questions regarding comfort during LPS. Crinone 8% had a clear advantage over Utrogest as it resulted in less vaginal discharge (P < 0.01) and fewer application difficulties (P<0.05). Twenty patients familiar with the alternative preparation from a previous cycle also noted that Crinone 8% was easier to apply (P < 0.01) and less time consuming (P < 0.05) to use than Utrogest.

Abortion, Spontaneous↗
PubMed2002

Gonadotrophin-releasing hormone (GnRH) and GnRH agonists: mechanisms of action.

The hypothalamic decapeptide gonadotrophin-releasing hormone (GnRH) binds to specific receptors on pituitary gonadotrophs. These receptors belong to the family of G protein-coupled receptors. Their activation leads to phosphoinositide breakdown with generation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and diacylglycerol. These second messengers initiate Ca2+ release from intracellular stores and activation of protein kinase C, both of which are important for gonadotrophin secretion and synthesis. Prolonged activation of GnRH receptors by GnRH leads to desensitization and consequently to suppressed gonadotrophin secretion. This is the primary mechanism of action of agonistic GnRH analogues. By contrast, GnRH antagonists compete with GnRH for receptors on gonadotroph cell membranes, inhibit GnRH-induced signal transduction and consequently gonadotrophin secretion. These compounds are free of agonistic actions, which might be beneficial in certain clinical applications.

Female↗
PubMed2002

Tailoring the GnRH antagonist cetrorelix acetate to individual patients' needs in ovarian stimulation for IVF: results of a prospective, randomized study.

INTRODUCTION: This study was performed to evaluate whether a tailored approach to the administration of the GnRH antagonist cetrorelix acetate according to follicular size leads to a reduction in the amount of Cetrotide vials used and/or an increased number of monitoring visits. METHODS: Sixty patients were prospectively randomized (using sealed envelopes) to receive either the fixed multiple dose antagonist protocol starting on day 6 of stimulation (group 1), or an individualized protocol with the time of antagonist start according to follicle size (14 mm, group 2), or an individualized single dose protocol (group 3). Recombinant human (rh)FSH was used. The primary endpoints were the number of Cetrotide vials and number of monitoring visits. Statistical power for the parameter Cetrotide vials was 80%. RESULTS: Patients in group 1 needed significantly more Cetrotide vials (6.81 +/- 1.61) than patients of group 2 (4.59 +/- 1.65; P < 0.01). The number of monitoring visits was similar between the three groups. Surprisingly, the number of retrieved oocytes was significantly higher in the individualized groups as compared with group 1. Despite a significantly lower total amount of rhFSH used, estradiol levels were significantly higher in group 2 as compared with group 1. CONCLUSION: Tailoring of GnRH antagonist protocols leads to an optimization of ovarian stimulation with more oocytes retrieved despite less rhFSH used, and the same number of monitoring visits.

Adult↗
PubMed2002

The effect of complete decongestive therapy on the quality of life of patients with peripheral lymphedema.

Lymphedema is a chronic disorder which can adversely affect quality of life (QOL). The purpose of this study was 1) to evaluate whether QOL was improved in patients with lymphedema following Complete Decongestive Therapy (CDT), and 2) whether limb volume change as a result of treatment correlated with change in QOL. Thirty-six patients with peripheral lymphedema from varying causes were enrolled in the study. The QOL of each participant, with regard to physical, functional, and psychosocial concerns, was measured by pre- and post-treatment questionnaires. Percent edema volume reduction was calculated for each patient with only one affected limb. QOL pre- and post-treatment scores were assessed by multivariate repeated measures analysis. QOL scores differed significantly (p<0.05) between pre- and posttreatment in all areas of inquiry. Patients with lower extremity lymphedema had significantly greater mean improvement in QOL scores compared with patients with upper extremity lymphedema (p=0.02). There was no correlation between percent edema volume reduction and post-treatment QOL improvement. This study suggests that significant improvements are made in the QOL of patients exhibiting peripheral lymphedema following CDT, which is not necessarily correlated with limb volume reduction.

Adult↗
PubMed2001

Osteopontin is involved in the initiation of cutaneous contact hypersensitivity by inducing Langerhans and dendritic cell migration to lymph nodes.

Osteopontin (OPN) is a chemotactic protein that attracts immune cells, to inflammatory sites. The sensitization phase of allergic cutaneous contact hypersensitivity (CHS) requires the migration of Langerhans cells/dendritic cells (LCs/DCs) from skin to draining lymph nodes. Characterizing OPN function for LC/DC migration we found upregulated OPN expression in hapten sensitized skin and draining lymph nodes. OPN induces chemotactic LC/DC migration, initiates their emigration from the epidermis, and attracts LCs/DCs to draining lymph nodes by interacting with CD44 and alphav integrin. Furthermore, OPN-deficient mice have a significantly reduced CHS response that correlates with an impaired ability of OPN-deficient mice to attract LCs/DCs to draining lymph nodes. In conclusion, OPN is an important factor in the initiation of CHS by guiding LCs/DCs from skin into lymphatic organs.

Animals↗