A Patient with speechlessness and rhabdomyolysis: a rare presentation of severe hypocalcaemia.

A 29-year-old man with no medical history presented to our emergency department with episodes of sudden speechlessness, hoarseness, vomiting after drinking cold water and spasms of his hands. Chvostek's and Trousseau's signs were both seen at presentation. Blood tests revealed severe hypocalcaemia (1.

Selecting the optimal position of CDK4/6 inhibitors in hormone receptor-positive advanced breast cancer - the SONIA study: study protocol for a randomized controlled trial.

Background: Combining cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors with endocrine therapy is an effective strategy to improve progression-free survival in hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. There is a lack of comparative data to help clinicians decide if CDK4/6 inhibitors can best be added to first- or second-line endocrine therapy. Improvement in median progression-free survival in first-line studies is larger than in second-line studies, but CDK4/6 inhibitors have not consistently shown to improve overall survival or quality of life.

Thyrostimulin Regulates Osteoblastic Bone Formation During Early Skeletal Development.

The ancestral glycoprotein hormone thyrostimulin is a heterodimer of unique glycoprotein hormone subunit alpha (GPA)2 and glycoprotein hormone subunit beta (GPB)5 subunits with high affinity for the TSH receptor. Transgenic overexpression of GPB5 in mice results in cranial abnormalities, but the role of thyrostimulin in bone remains unknown. We hypothesized that thyrostimulin exerts paracrine actions in bone and determined: 1) GPA2 and GPB5 expression in osteoblasts and osteoclasts, 2) the skeletal consequences of thyrostimulin deficiency in GPB5 knockout (KO) mice, and 3) osteoblast and osteoclast responses to thyrostimulin treatment.

Thyrostimulin deficiency does not alter peripheral responses to acute inflammation-induced nonthyroidal illness.

Thyrostimulin, a putative glycoprotein hormone, comprises the subunits GPA2 and GPB5 and activates the TSH receptor (TSHR). The observation that proinflammatory cytokines stimulate GPB5 transcription suggested a role for thyrostimulin in the pathogenesis of nonthyroidal illness syndrome (NTIS). In the present study, we induced acute inflammation by LPS administration to GPB5(-/-) and WT mice to evaluate the role of thyrostimulin in peripheral thyroid hormone metabolism during NTIS.

Reduced by-product formation and modified oxygen availability improve itaconic acid production in Aspergillus niger.

Aspergillus niger has an extraordinary potential to produce organic acids as proven by its application in industrial citric acid production. Previously, it was shown that expression of the cis-aconitate decarboxylase gene (cadA) from Aspergillus terreus converted A. niger into an itaconic acid producer (Li et al.

Complete inhibition of rhTSH-, Graves' disease IgG-, and M22-induced cAMP production in differentiated orbital fibroblasts by a low-molecular-weight TSHR antagonist.

The TSH receptor (TSHR) on orbital fibroblasts (OF) is a proposed target of the autoimmune attack in Graves' ophthalmopathy. In the present study, we tested whether the novel low-molecular-weight (LMW) TSHR antagonist Org-274179-0 inhibits cAMP production induced by rhTSH, Graves' disease IgG (GD-IgG), or M22 (a potent human monoclonal TSHR stimulating antibody) in cultured and differentiated OF from Graves' ophthalmopathy patients. cAMP production significantly increased after incubation either with 10 mU/ml rhTSH (3-fold; P ≤ 0.

Optimal management of Graves orbitopathy: a multidisciplinary approach.

Graves' thyroid disease is a relatively common disorder in endocrinology and general internal medicine practice. Graves' hyperthyroidism is mediated by circulating stimulating autoantibodies. Up to 60% of patients with Graves' hyperthyroidism develop some form of Graves' orbitopathy.

Acute inflammation increases pituitary and hypothalamic glycoprotein hormone subunit B5 mRNA expression in association with decreased thyrotrophin receptor mRNA expression in mice.

The biological function of thyrostimulin, consisting of the GPA2 and GPB5 subunit, is currently poorly understood. The recent observation that pro-inflammatory cytokines up-regulate the transcription of GPB5 in vitro suggested a role for thyrostimulin in the nonthyroidal illness syndrome, a state of altered thyroid hormone metabolism occurring during illness. In the present study, we used GPB5 knockout (GPB5(-/-) ) and wild-type (WT) mice to evaluate the role of GPB5 in the pituitary and hypothalamus during acute inflammation induced by lipopolysaccharide (LPS, bacterial endotoxin) administration.

Thyrotropin receptor-stimulating Graves' disease immunoglobulins induce hyaluronan synthesis by differentiated orbital fibroblasts from patients with Graves' ophthalmopathy not only via cyclic adenosine monophosphate signaling pathways.

Background: Both expression of the thyrotropin receptor (TSHR) and the production of hyaluronan (HA) by orbital fibroblasts (OF) have been proposed to be implicated in the pathogenesis of Graves' ophthalmopathy (GO). HA is synthesized by three types of HA synthase. We hypothesized that TSHR activation by recombinant human TSH (rhTSH) and TSHR-stimulating Graves' disease immunoglobulins (GD-IgGs) via induced cyclic adenosine monophosphate (cAMP) signaling increases HA synthesis in differentiated OF from GO patients.

Effects of thyrotropin and thyrotropin-receptor-stimulating Graves' disease immunoglobulin G on cyclic adenosine monophosphate and hyaluronan production in nondifferentiated orbital fibroblasts of Graves' ophthalmopathy patients.

Background: Orbital fibroblasts are involved in the pathogenesis of Graves' ophthalmopathy (GO) by producing hyaluronan (HA), synthesized by three types of hyaluronan synthases (HAS1, HAS2, and HAS3). Thyrotropin receptors (TSHR) expressed in orbital fibroblasts activate the cyclic adenosine monophosphate (cAMP) pathway. Only sparse data are available at present supporting a role for TSHR activation in the regulation of HA in GO orbital fibroblasts.

Transient hypothyroxinemia in juvenile glycoprotein hormone subunit B5 knock-out mice.

The heterodimer thyrostimulin, comprised of two novel glycoprotein hormone subunits GPA2 and GPB5, activates the TSH receptor. To understand its role in the regulation of the hypothalamus-pituitary-thyroid (HPT-) axis, we evaluated juvenile and adult GPB5 knock-out (GPB5(-/-)) and wild type mice (WT) during euthyroidism, hypothyroidism and thyrotoxicosis. Surprisingly, juvenile euthyroid GPB5(-/-) mice displayed marked hypothyroxinemia (25% lower serum T(4), unchanged TSH) and also during thyrotoxicosis juvenile GPB5(-/-) mice had 25% lower serum T(4), compared to WT.

Identification and characterization of a family of secretion-related small GTPase-encoding genes from the filamentous fungus Aspergillus niger: a putative SEC4 homologue is not essential for growth.

DNA fragments containing genetic information for five secretion-related small GTPases of Aspergillus niger (srgA-E) were isolated and identified as members of different Rab/Ypt subfamilies. This isolation and the search for similar sequences in fungal genomic and EST databases showed that, in contrast to Saccharomyces cerevisiae, filamentous fungi also possess homologues of mammalian Rab2 GTPases. Multiple transcripts with unusually long 5' and 3' untranslated regions were found for all srg genes.

First experiences with an accelerated CMV antigenemia test: CMV Brite Turbo assay.

Background: Cytomegalovirus disease is still a major problem in immunocompromised patients, such as bone marrow or kidney transplantation patients. The detection of viral antigen in leukocytes (antigenemia) has proven to be a clinically relevant marker of CMV activity and has found widespread application. Because most existing assays are rather time-consuming and laborious, an accelerated version (Brite Turbo) of an existing method (Brite) has been developed.

Clinical outcome and follow-up of sonographically suspected in utero urinary tract anomalies.

Purpose: We determined the outcome of pregnancy and long-term renal function in cases of sonographically detected fetal urinary tract anomalies (UTAs).

Methods: This was a retrospective cohort study done at an academic hospital (tertiary referral center). All records of prenatal sonographic examinations done between January 1985 and October 1994 that indicated a suspicion for UTA were examined for perinatal mortality, postnatal confirmation of sonographic diagnosis, postnatal management, and calculated creatinine clearance to determine the ultimate renal function.

An improved colony-PCR method for filamentous fungi for amplification of PCR-fragments of several kilobases.

A method was developed to perform PCR directly on mycelial pellets or colonies treated with NOVOzym 234. The method allows rapid screening of large numbers of transformants of both sporulating and non-sporulating fungi for the presence of (co)transforming plasmid copies or for specific genetic modifications such as gene disruption and site specific integration. PCR fragments of at least 3.

Cloning and characterization of the NADPH cytochrome P450 oxidoreductase gene from the filamentous fungus Aspergillus niger.

In this paper, we describe the cloning and molecular characterization of the Aspergillus niger cytochrome P450 reductase (CPR) gene, cprA. Attempts to clone the cprA gene by heterologous hybridization techniques were unsuccessful. Using the polymerase chain reaction (PCR) with degenerate primers based on conserved regions found in cpr genes from other organisms, we were able to isolate a fragment that contained part of the gene.

Cloning, characterization and overexpression of the phytase-encoding gene (phyA) of Aspergillus niger.

Phytase catalyzes the hydrolysis of phytate (myo-inositol hexakisphosphate) to myo-inositol and inorganic phosphate. A gene (phyA) of Aspergillus niger NRRL3135 coding for extracellular, glycosylated phytase was isolated using degenerate oligodeoxyribonucleotides deduced from phytase amino acid (aa) sequences. Nucleotide (nt) sequence analysis of the cloned region revealed the presence of an open reading frame coding for 467 aa and interrupted once by an intron of 102 bp in the 5' part of the gene.

Development of a new transformant selection system for Penicillium chrysogenum: isolation and characterization of the P. chrysogenum acetyl-coenzyme A synthetase gene (facA) and its use as a homologous selection marker.

A new transformation system for the filamentous fungus Penicillium chrysogenum is described, based on the use of the homologous acetyl-coenzyme A synthetase (facA) gene as a selection marker. Acetate-non-utilizing (Fac-) strains of P. chrysogenum were obtained by positive selection for spontaneous resistance to fluoroacetate.

Development of a homologous transformation system for Aspergillus niger based on the pyrG gene.

The development of a homologous transformation system for Aspergillus niger is described. The system is based on the use of an orotidine-5'-phosphate decarboxylase deficient mutant (pyrG) and a vector, pAB4-1, which contains the functional A. niger pyrG gene as a selection marker.