Towards a Consensus on Alzheimer's Disease Comorbidity?

Alzheimer's disease (AD) is often comorbid with other pathologies. First, we review shortly the diseases most associated with AD in the clinic. Then we query PubMed citations for the co-occurrence of AD with other diseases, using a list of 400 common pathologies.

A novel candidate cis-regulatory motif pair in the promoters of germline and oogenesis genes in C. elegans.

In this study we report on a novel pair of cis-regulatory motifs in promoter sequences of the nematode Caenorhabditis elegans. The motif pair exhibits extraordinary genomic traits: The order and the orientation of the two motifs are highly specific, and the distance between them is almost always one of two frequent distances. In contrast, the sequence between the motifs is variable across occurrences.

Allegro: analyzing expression and sequence in concert to discover regulatory programs.

A major goal of system biology is the characterization of transcription factors and microRNAs (miRNAs) and the transcriptional programs they regulate. We present Allegro, a method for de-novo discovery of cis-regulatory transcriptional programs through joint analysis of genome-wide expression data and promoter or 3' UTR sequences. The algorithm uses a novel log-likelihood-based, non-parametric model to describe the expression pattern shared by a group of co-regulated genes.

Transcription factor and microRNA motif discovery: the Amadeus platform and a compendium of metazoan target sets.

We present a threefold contribution to the computational task of motif discovery, a key component in the effort of delineating the regulatory map of a genome: (1) We constructed a comprehensive large-scale, publicly-available compendium of transcription factor and microRNA target gene sets derived from diverse high-throughput experiments in several metazoans. We used the compendium as a benchmark for motif discovery tools. (2) We developed Amadeus, a highly efficient, user-friendly software platform for genome-scale detection of novel motifs, applicable to a wide range of motif discovery tasks.

Functional genomic delineation of TLR-induced transcriptional networks.

Background: The innate immune system is the first line of defense mechanisms protecting the host from invading pathogens such as bacteria and viruses. The innate immunity responses are triggered by recognition of prototypical pathogen components by cellular receptors. Prominent among these pathogen sensors are Toll-like receptors (TLRs).

Down-regulation of type II L-thyroxine, 5'-monodeiodinase in cultured GC cells: different pathways of regulation by L-triiodothyronine and 3,3',5'-triiodo-L-thyronine.

The current consensus is that iodothyronines down-regulate type II T4 monodeiodinase (5'-DII) by an extranuclear acceleration of enzyme inactivation. We have investigated 5'-DII regulation in cultured GC cells, in which thyroid hormone responses are mediated by nuclear thyroid receptor (TR). GC cells actively converted T4 to T3, independent of propylthiouracil and with a Km of 1.

Role of L-thyroxine in nuclear thyroid hormone receptor occupancy and growth hormone production in cultured GC cells.

The contribution of L-thyroxine (T4) to nuclear thyroid receptor occupancy was studied in GC cells incubated with concentrations of 3,5,3'-triiodo-L-thyronine (T3) and T4 that resulted in free iodothyronine levels similar to those in serum of euthyroid rats. T4 accounted for 5.4-10% of the occupied receptors: T3 derived from T4 [T3(T4)] and T3 added to medium accounted for the remainder of receptor occupancy.

Acromegaly due to ectopic growth hormone-releasing hormone secretion by a bronchial carcinoid tumour. Dynamic hormonal responses to various stimuli.

Ectopic GHRH is a relatively uncommon cause of acromegaly, which should be differentiated from pituitary adenoma, in order to avoid damage to the pituitary gland from unnecessary interventions. We report here on a 66-year-old man with acromegaly due to a GHRH-secreting bronchial carcinoid tumour, who recovered completely following removal of the tumour. His hormonal status was studied before and after the operation.

Medium 3,5,3'-triiodo-L-thyronine (T3) and T3 generated from L-thyroxine are exchangeable in cultured GC cells.

Previous studies in rats have shown that the ratio anterior pituitary nuclear L-triiodothyronine (T3) derived from intracellular deiodination of L-thyroxine [T3(T4)]/plasma T3(T4) is much greater than for exchangeable T3 [T3(T3)]. We have addressed the hypothesis that T3(T4) is either selectively accumulated or selectively retained by nuclei in comparison to exchangeable T3 [T3(T3)] in cultured GC cells. GC cells readily generated T3 from T4.

L-triiodothyronine (T3) regulates cellular growth rate, growth hormone production, and levels of nuclear T3 receptors via distinct dose-response ranges in cultured GC cells.

Cultured rat somatotrophic cells have been useful models for the study of thyroid hormone action. A consensus of previous reports has indicated that approximately 0.2 nM T3 results in 50% occupancy of T3 nuclear receptors as well as half-maximal stimulation of several T3 responses.

Chronic treatment of a benign insulinoma using the long-acting somatostatin analogue SMS 201-995.

The newly developed long-acting somatostatin analogue SMS 201-995 was used to treat a patient with the presumptive diagnosis of benign insulinoma. Although intermittent injections with 50-100 micrograms s.c.

Development and characterization of a variant GC cell line with L-triiodothyronine-independent growth and growth hormone production.

To facilitate studies of cell growth regulation by T3, we developed a variant GC cell line (V-GC) characterized by normal growth in T3-depleted (-T3) medium. The doubling time (dt) of V-GC cells was 28.8 h (-T3) and 28.

Bromocriptine treatment of acromegaly: possible dose dependency of the tumor size-reducing effect.

The effect of long-term, high-dose therapy with bromocriptine (BR) on the clinical and hormonal response, tumor size and neuro-ophthalmological status was studied in seven acromegalic patients. The mean BR dose was 64 mg/day (range 35 to 80) for a mean period of 11 months (range 10 to 12). In six patients there was a clinical improvement already manifest at low BR doses (10 to 20 mg).

Medical treatment of primary hyperparathyroidism: effects on parathormone and vitamin D metabolites.

A 63-year-old woman was treated medically for primary hyperparathyroidism because of a recent myocardial infarction. She received propranolol alone or combined with either cimetidine, calcitonin or disodium etidronate (EHDP). The treatment did not affect the elevated serum parathormone or urinary cyclic AMP levels, nor did it correct the elevated serum 1,25(OH)2D and the decreased serum 24,25(OH)2D levels in this patient.

Acute desensitization of lymphocyte beta-adrenergic-stimulated adenylate cyclase in old age and Alzheimer's disease.

The effect of prior incubation with a single concentration of isoproterenol (10(-4) M) for 2 hours at 37 degrees C on isoproterenol-stimulated cyclic AMP accumulation in intact lymphocytes from young, old and subjects with Alzheimer's disease was studied. In lymphocytes from all three subjects groups prior incubation of cells with isoproterenol resulted in a significant reduction of cyclic AMP accumulation upon subsequent stimulation with isoproterenol.

A predictor index for hospitalization for patients with acute asthmatic attack.

Thirty-nine patients, aged 14 to 50 years (mean 33), were treated for an acute asthmatic attack in the hospital emergency room. A scored index was estimated on admission for each patient, based on pulse, respiratory and peak expiratory flow rates (PEFR), amplitude of paradoxical pulse and degree of dyspnea, wheezing and accessory muscle use. All patients were treated according to a standard protocol including oxygen, fluids, salbutamol inhalations and aminophylline infusions, with hydrocortisone infusion in selected patients.

Prolactin response to metoclopramide and chlorpromazine in primary testicular failure and isolated gonadotrophin deficiency.

The aim of the present study was to measure the PRL response to metoclopramide (MET) and chlorpromazine (CPZ) in seventeen patients with primary testicular failure and eight patients with isolated gonadotrophin deficiency (IGD). The responses were compared with those to TRH. Basal gonadotrophins and peak responses to LHRH were increased in testicular failure and reduced in IGD.

Surgical management of periadnexal adhesions.

The importance of the lysis of periadnexal adhesions with regard to pregnancy rate was evaluated in 101 infertile patients. All patients had at least one patent tube and normal fimbria. The periadnexal adhesions were classified into four grades according to their nature and extent.