A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder.

Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule.

Prolactin and oleic acid synergistically stimulate β-cell proliferation and growth in rat islets.

Islet adaptation to pregnancy is largely influenced by prolactin and placental lactogens. In addition serum lipids are significantly increased. Here, we report the novel observation that prolactin and oleic acid synergistically stimulate islet cell proliferation and islet growth.

Cognitive outcome after ventral capsule/ventral striatum stimulation for treatment-resistant major depression.

Background: We report the neuropsychological outcome of 25 patients with treatment-resistant major depressive disorder (TRD) who participated in an Institutional Review Board (IRB)-approved randomised double-blind trial comparing active to sham deep brain stimulation (DBS) in the anterior limb of the ventral capsule/ventral striatum (VC/VS).

Methods: Participants were randomised to active (n=12) versus sham (n=13) DBS for 16 weeks. Data were analysed at the individual and group levels.

A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression.

Background: Multiple open-label trials of deep brain stimulation (DBS) for treatment-resistant depression (TRD), including those targeting the ventral capsule/ventral striatum target, have shown encouraging response rates. However, no randomized controlled trials of DBS for TRD have been published.

Methods: Thirty patients with TRD participated in a sham-controlled trial of DBS at the ventral capsule/ventral striatum target for TRD.

Beneficial effects of lipids and prolactin on insulin secretion and beta-cell proliferation: a role for lipids in the adaptation of islets to pregnancy.

To meet the increased demand for insulin during pregnancy, the pancreatic islets undergo adaptive changes including enhanced insulin secretion and beta-cell proliferation. These changes peak in mid-pregnancy and return to control levels by parturition. Because lactogens (placental lactogen and/or prolactin) induce this up-regulation and remain elevated throughout gestation, we examined whether lipids alter the effects of prolactin on islets.

Regulation of glucokinase in pancreatic islets by prolactin: a mechanism for increasing glucose-stimulated insulin secretion during pregnancy.

Glucokinase activity is increased in pancreatic islets during pregnancy and in vitro by prolactin (PRL). The underlying mechanisms that lead to increased glucokinase have not been resolved. Since glucose itself regulates glucokinase activity in beta-cells, it was unclear whether the lactogen effects are direct or occur through changes in glucose metabolism.

Immunohistochemical evidence for the presence of glucokinase in the gonadotropes and thyrotropes of the anterior pituitary gland of rat and monkey.

A recent report provides new evidence for the presence of glucokinase (GK) in the anterior pituitary. In the present study, immunohistochemistry was used to identify the cells containing GK in the pituitary of rats and monkeys. In rats, GK was detected as a generalized cytoplasmic staining in a discrete population of cells in the anterior pituitary.

Distinctive roles for prolactin and growth hormone in the activation of signal transducer and activator of transcription 5 in pancreatic islets of langerhans.

Although the beta-cells of the pancreatic islets of Langerhans express both prolactin (PRL) and GH receptors, we have observed that PRL is considerably more effective than GH in the up-regulation of islet function in vitro. This study examined whether differences in the activation of the Janus kinase 2/signal transducer and activator of transcription (STAT) 5 signaling pathway by these closely related receptors may be involved in this disparity. The activation of STAT5B by PRL was biphasic, with an initial peak within 30 min, a nadir between 1 and 3 h, and prolonged activation after 4 h.

The economic effect of hypoglycemia in a health plan.

This study was undertaken to determine the incidence and economic cost of hypoglycemia in patients with diabetes taking insulin in a large mid-western health plan. Analysis of claims data identified 7,659 members with a diagnostic code for either type 1 or type 2 diabetes during a seven-year interval from 1992 to 1998. A total of 2,118 were prescribed some type of insulin regimen.

An immunohistochemical approach to monitor the prolactin-induced activation of the JAK2/STAT5 pathway in pancreatic islets of Langerhans.

This study examined whether an immunohistochemical method examining the subcellular localization of STAT5 could be used to characterize the activation of the JAK2/STAT5 pathway by prolactin (PRL) in intact cells or tissues. In the Ins-1 beta-cell line, STAT5A and STAT5B were distributed almost equally in the cytoplasm and the nucleus in unstimulated cells. STAT5A was also detected along the border of cells and in the perinuclear region.

Dopamine-synthesizing neurons include the putative H-cell homologue in the moth Manduca sexta.

The catecholamine dopamine (DA) plays a fundamental role in the regulation of behavior and neurodevelopment across animal species. Uncovering the embryonic origins of neurons that express DA opens a path for a deeper understanding of how DA expression is regulated and, in turn, how DA regulates the activities of the nervous system. In a well-established insect model, Manduca sexta, we identified the putative homologue of the embryonic grasshopper "H-cell" using intracellular techniques, laser scanning confocal microscopy, and immunohistochemistry.

Dexamethasone counteracts the effect of prolactin on islet function: implications for islet regulation in late pregnancy.

Islets undergo a number of up-regulatory changes to meet the increased demand for insulin during pregnancy, including increased insulin secretion and beta-cell proliferation. It has been shown that elevated lactogenic hormone is directly responsible for these changes, which occur in a phasic pattern, peaking on day 15 of pregnancy and returning to control levels by day 20 (term). As placental lactogen levels remain elevated through late gestation, it was of interest to determine whether glucocorticoids (which increase during late gestation) could counteract the effects of lactogens on insulin secretion, beta-cell proliferation, and apoptosis.

Role of cAMP in upregulation of insulin secretion during the adaptation of islets of Langerhans to pregnancy.

Islets undergo a number of upregulatory changes to meet the increased demand for insulin during pregnancy, including an increase in glucose-stimulated insulin secretion with a reduction in the stimulation threshold. Treatment with the lactogenic hormone prolactin (PRL) in vitro has been shown to induce changes in islets similar to those observed during pregnancy. We examined cAMP production in islets treated with PRL to determine if changes in cAMP are involved in the upregulation of insulin secretion.

Adaptation of islets of Langerhans to pregnancy: beta-cell growth, enhanced insulin secretion and the role of lactogenic hormones.

Pregnancy is a unique event in the life span of islet beta-cells. Under the influence of pregnancy islet beta-cells undergo major long term up-regulatory structural and functional changes in response to the increased demand for insulin. Adaptive changes that occur in islets during normal pregnancy include: 1) increased glucose-stimulated insulin secretion with a lowered threshold for glucose-stimulated insulin secretion, 2) increased insulin synthesis, 3) increased beta-cell proliferation and islet volume, 4) increased gap-junctional coupling among beta-cells, 5) increased glucose metabolism, and 6) increased c-AMP metabolism.

Novel mouse IgG-like immunoreactivity expressed by neurons in the moth Manduca sexta: developmental regulation and colocalization with crustacean cardioactive peptide.

Immunoglobulin-related molecules have been shown to play important roles in cell-cell recognition events during the development of both vertebrate and invertebrate nervous systems. In the moth, Manduca sexta, we report the presence of novel, mouse, immunoglobulin G (mIgG)-like immunoreactivity in a discrete population of identified neurosecretory neurons (the NS-Ls also known as the cell 27s) and interneurons (the IN-704s). A number of polyclonal anti-mIgG antibodies were used to immunostain these cells in wholemount.

Evidence for the role of pancreatic acinar cells in the production of ornithine and guanidinoacetic acid by L-arginine:glycine amidinotransferase.

L-Arginine:glycine amidinotransferase (transamidinase) occurs at high concentrations in the kidney and the pancreas of rats. The cellular localization of transamidinase was investigated in fetal, neonatal, and adult rat pancreatic tissue using three indicators of the presence of transamidinase: (1) immunofluorescence microscopy, (2) in vitro enzymatic activity measurements on homogenates of whole pancreas and on isolated acinar and islet tissue from adult rats, and (3) ornithine production from perfused adult rat pancreas. The cellular localization of transamidinase was determined in fetal, neonatal, and adult rat pancreas, using a polyclonal guinea pig antibody made against a highly purified preparation of kidney transamidinase.

Innervation and vasculature of human sweat glands: an immunohistochemistry-laser scanning confocal fluorescence microscopy study.

Secreting tubules, nerves fibers, and blood vessels in human sweat glands (SGs) were fluorescently stained by immunohistochemical and lectin methods for examination with a laser scanning confocal microscope (LSCM). Using these techniques, the three-dimensional distribution of up to three substances within a single specimen was investigated by collecting a series of optical sections for each of three fluorophores. Each SG received several nerve fibers.

Effect of tyrosine kinase inhibitors on islets of Langerhans: evidence for tyrosine kinases in the regulation of insulin secretion.

In order to determine if tyrosine kinase activation is involved in the changes in islet function, the effect of tyrosine kinase inhibitors on insulin secretion and islet cell proliferation was examined in cultured islets of Langerhans. When islets were exposed to 100 microM genistein or 2 microM herbimycin A, large 5- to 10-fold increases in insulin secretion were observed. The effect on insulin secretion was detected within 1 hr and was maintained for at least 4 days.

Regulation of islet beta-cell proliferation by prolactin in rat islets.

This study examined the effects of prolactin on beta-cell proliferation in pancreatic islet of Langerhans. Insulin secretion and beta-cell proliferation were significantly increased from neonatal rat islets cultured for 4 days in the presence of either 500 ng/ml ovine prolactin (oPRL) or rat prolactin (rPRL). These effects could be prevented by including anti-oPRL serum in the culture media.

Effects of steroid and lactogenic hormones on islets of Langerhans: a new hypothesis for the role of pregnancy steroids in the adaptation of islets to pregnancy.

Adaptive changes that occur in islets of Langerhans during pregnancy include enhanced insulin secretion, insulin synthesis, beta-cell proliferation, gap-junctional coupling among beta-cells, and glucose oxidation. We have determined that elevated lactogenic activity is directly responsible for these changes in beta-cell function. Recently, we showed that two of the principal adaptive characteristics (insulin secretion and beta-cell proliferation) of rat pregnancy peaked on day 15 and returned to control levels by day 20.

Improvements for the anatomical characterization of insect neurons in whole mount: the use of cyanine-derived fluorophores and laser scanning confocal microscopy.

The optical sectioning capability of the laser scanning confocal microscope was utilized to image dye-filled neurons within whole-mounted insect ganglia. Specific pterothoracic interneurons, in the moth Manduca sexta, were retrogradely filled with Neurobiotin and subsequently visualized with a monoclonal anti-biotin conjugated with one of the following fluorophores: fluorescein, and the newly developed cyanines, Cy3.18 (Cy3) and Cy5.

Effect of homologous placental lactogens, prolactins, and growth hormones on islet B-cell division and insulin secretion in rat, mouse, and human islets: implication for placental lactogen regulation of islet function during pregnancy.

Up-regulation of maternal islet function is essential to accommodate the increased demand for insulin during pregnancy. Previously, we suggested that lactogenic activity regulates islet function during pregnancy. However, this hypothesis was based on the effect of homologous PRLs on islets, since the homologous placental lactogens (or islets) were unavailable.