Bcl-xL antisense oligonucleotides chemosensitize human glioblastoma cells.

Background: Resistance to chemotherapy in glioblastoma has been linked to the expression of antiapoptotic Bcl-2 family members including Bcl-xL.

Methods: Bcl-xL expression was specifically reduced in M059K glioblastoma cells with antisense oligonucleotides (ISIS 16009, ISIS 16967) as assessed by Western blotting. Induction of apoptosis by treatment with antisense oligonucleotides in combination with paclitaxel in cell culture was monitored by WST-1 assays and flow cytometric analysis.

Varying additive effects of bromocriptine with two somatostatin analogs in cultures of GH-secreting adenomas.

In this study, we have investigated the effect of combined treatment using two somatostatin analogs, lanreotide or octreotide, with bromocriptine on GH release in cultures of GH-secreting pituitary tumors. Sixteen acromegalic patients were included in the study. All patients had been treated with lanreotide prior to the surgery.

Acromegaly Quality of Life Questionnaire (ACROQOL) a new health-related quality of life questionnaire for patients with acromegaly: development and psychometric properties.

Objective: To develop a disease-specific questionnaire suitable to measure health-related quality of life (HRQOL) in acromegaly (ACROQOL).

Design, Patients And Measurements: For the development of the ACROQOL questionnaire different sources of information were used: First, a literature search was performed to identify relevant papers describing the impact of acromegaly in HRQOL. Second, 10 endocrinologists identified the main domains of impact on HRQOL in patients with acromegaly.

Protein kinase C isoforms in normal and transformed cells of the melanocytic lineage.

Enzymes belonging to the protein kinase C (PKC) family represent one of the major mediators of signal transduction in melanocytes. To identify PKC isoforms that may be associated with the process of malignant transformation and metastasis, we investigated the expression pattern of 11 different PKC isoforms (alpha, beta I, beta II, gamma, delta, epsilon, eta, theta, zeta, lambda, and iota) in melanoma lymph node metastases, in cell lines established from these metastases, in primary cell cultures from normal melanocytes, and in permanent cell lines established from spontaneously transformed melanocytes. PKC alpha, beta I, beta II, delta, epsilon, eta, zeta, lambda and iota were found to be expressed in total lysates from melanoma metastases.

Connexin 26 mutations in cases of sensorineural deafness in eastern Austria.

Mutations in the connexin 26 (Cx26) gene (GJB2) are associated with autosomal nonsyndromic sensorineural hearing loss. This study describes mutations in the Cx26 gene in cases of familial and sporadic hearing loss (HL) by gene sequencing and identifies the allelic frequency of the most common mutation leading to HL (35delG) in the population of eastern Austria. For this purpose we have developed and applied a molecular beacon based real-time mutation detection assay.

The addition of hydromorphone to epidural fentanyl does not affect analgesia in early labour.

Purpose: Epidural fentanyl after a lidocaine and epinephrine test dose, provides adequate analgesia and allows for ambulation during early labour. The current study was designed to determine the influence of hydromorphone added to an epidural fentanyl bolus (e.g.

GEM 231, a second-generation antisense agent complementary to protein kinase A RIalpha subunit, potentiates antitumor activity of irinotecan in human colon, pancreas, prostate and lung cancer xenografts.

GEM 231, a second-generation antisense oligonucleotide targeted against the RIalpha subunit of protein kinase A (PKA) was co-administered with the chemotherapeutic agent irinotecan, a topoisomerase-I inhibitor, to study the antitumor efficacy of the combination in nude mice bearing various human tumor xenografts. The combination treatment of GEM 231 and irinotecan produced enhanced and prolonged tumor-growth inhibition, compared with irinotecan monotherapy, against human colon (HCT-116), pancreas (Panc-1), prostate (PC3) and lung (SKMES) tumors in mice. The extent of tumor-growth inhibition, however, varied among the different tumor models studied.

The constitutive expression of galectin-3 is downregulated in the intestinal epithelia of Crohn's disease patients, and tumour necrosis factor alpha decreases the level of galectin-3-specific mRNA in HCT-8 cells.

Objective: Galectin-3, a lectin with specificity for beta galactoside, is expressed by a variety of cells, including intestinal epithelial cells. Among other functions, galectin-3 mediates cell adhesion and is involved in inflammatory processes. In this study, we assessed the expression of galectin-3 in intestinal epithelial cells from Crohn's disease patients (n = 10), ileum adjacent to resected colon carcinoma (n = 9), unspecific bowel inflammation (n = 1), diverticulosis (n = 1), ulcerative colitis (n = 3) and healthy jejunum used for interposition in larynx carcinoma (n = 1).

Bcl-X(L) is a chemoresistance factor in human melanoma cells that can be inhibited by antisense therapy.

Malignant melanoma is a tumor that responds poorly to a variety of apoptosis-inducing treatment modalities, such as chemotherapy. The expression of genes that regulate apoptotic cell death plays an important role in determining the sensitivity of tumor cells to chemotherapeutic intervention. Bcl-x(L) is an antiapoptotic member of the Bcl-2 family and is universally expressed in human melanoma.

The melanocyte-specific isoform of the microphthalmia transcription factor affects the phenotype of human melanoma.

The microphthalmia transcription factor MITF plays a pivotal role in the development and differentiation of melanocytes. The purpose of this work was to investigate the expression and function of the melanocyte-specific isoform MITF-M in human melanoma. We found that MITF-M is repressed in 8 of 14 established melanoma cell lines tested.

Is unilateral adrenalectomy an alternative treatment for ACTH-independent macronodular adrenal hyperplasia?: Long-term follow-up of four cases.

Objective: ACTH-independent macronodular adrenal hyperplasia is a rare cause of Cushing's syndrome. Bilateral adrenalectomy is considered the treatment of choice, but the patient is obliged to receive lifetime steroid replacement therapy and is susceptible to adrenal insufficiency crisis. New therapeutic alternatives are being proposed as new etiopathological features of the disease are known.

MEN-2A syndrome and pulmonary metastasis.

A case of multiple endocrine neoplasia syndrome type-2A (MEN-2A) with primary hyperparathyroidism and medullary carcinoma of thyroid initially treated by surgery is reported. The presence of pulmonary nodules six years after the initial treatment was thought to be related to metastasis of medullary carcinoma, and the increase in serum calcium concentrations was assumed to be caused by persistence of parathyroid adenomatous or hyperplastic tissue. The patient underwent surgery again and the pulmonary nodules were confirmed to be metastases of a parathyroid carcinoma, a very rare entity in MEN-2A syndrome.

The complete normalization of the adrenocortical function as the criterion of cure after transsphenoidal surgery for Cushing's disease.

Transsphenoidal microsurgery is the standard treatment for patients with Cushing's disease. However, there is general lack of agreement regarding the definition of cure. We studied 58 patients with corrected hypercortisolism after transsphenoidal surgery for Cushing's disease.

Bcl-2 antisense oligonucleotides chemosensitize human gastric cancer in a SCID mouse xenotransplantation model.

We used Bcl-2 antisense oligonucleotides (G3139) to chemosensitize human gastric cancer by downregulation of Bcl-2 expression in vivo. Oligonucleotides and cisplatin were administered systemically in a human gastric cancer SCID mouse model, and Bcl-2 expression, apoptosis, tumor size, and survival were assessed. Used alone, G3139 treatment led to downregulation of Bcl-2 and moderate tumor reduction compared to saline control.

Transbronchial biopsy with virtual CT bronchoscopy and nodal highlighting.

Transbronchial biopsy to sample lymph nodes and tumors that are not visible at endoscopy has a poor (<50%) success rate. These nodes can be highlighted easily at virtual computed tomographic (CT) bronchoscopy to provide a guide. This study was performed to evaluate if the addition of this information to the bronchoscopist improved the success rate of transbronchial biopsy of subcarinal and aortopulmonary lymph nodes.

The influence of a bupivacaine and fentanyl epidural infusion after epidural fentanyl in patients allowed to ambulate in early labor.

Unlabelled: Epidural fentanyl after a lidocaine and epinephrine test dose provides adequate analgesia and allows for ambulation during early labor. This study was designed to determine the influence of an epidural infusion of bupivacaine plus fentanyl administered after initiation of epidural labor analgesia with fentanyl. Specifically, we evaluated whether there is an increase in motor block or an increased time to request for further analgesic medication.

Elevated procaspase levels in human melanoma.

In this study procaspase expression levels were investigated by Western blotting in a panel of established melanoma cell lines, transformed melanocytic cell lines and normal primary melanocytes. Upstream caspases such as procaspase-8 that contain a death effector domain were found to be overexpressed in transformed melanocytes and melanoma cell lines compared with melanocytes. Heterogeneous levels of procaspase-8 were seen in melanoma cells, including one cell line that completely lacked procaspase-8 expression.

Differential expression levels of Par-4 in melanoma.

The pro-apoptotic prostate apoptosis response-4 gene product Par-4 sensitizes prostate cells to the induction of programmed cell death. In this study we examined Par-4 expression in human melanoma cell lines and melanoma metastases. The heterogeneous expression detected prompted us to investigate the biological relevance of Par-4 in a human melanoma xenotransplantation model.

Predictors of breakthrough pain during labor epidural analgesia.

Unlabelled: Parturients who receive labor epidural analgesia may experience breakthrough pain that requires supplemental medications. We investigated the factors associated with breakthrough pain. This prospective observational study included 1963 parturients who received epidural analgesia.

Estrogens decrease reperfusion-associated cortical ischemic damage: an MRI analysis in a transient focal ischemia model.

Background And Purpose: Early identification of irreversible cerebral ischemia is critical in defining strategies that influence neuronal survival after stroke. We used MRI to investigate the effects of 17beta-estradiol (E2) on the temporal evolution of focal ischemia.

Methods: Female rats were ovariectomized and divided into 1 of 2 groups: ovariectomy alone (OVX; n=4) or ovariectomy with estrogen replacement (OVX+E2; n=3).

Fracture dislocations of the elbow in athletes.

Elbow dislocations can result in extensive injury to the supporting structures of the elbow joint. Principles of treatment include prompt reduction of the dislocation and treatment of associated fractures. The goal is to restore joint stability and to allow for early mobility.

Chemosensitisation of malignant melanoma by BCL2 antisense therapy.

Background: Chemoresistance of malignant melanoma has been linked to expression of the proto-oncogene BCL2. Antisense oligonucleotides (ASO) targeted against BCL2 mRNA decreased BCL2 protein concentrations, increased tumour-cell apoptosis, and led to tumour responses in a mouse xenotransplantation model when combined with systemic dacarbazine. This phase I-II clinical study investigated the combination of BCL2 ASO (augmerosen, Genasense, G3139) and dacarbazine in patients with advanced malignant melanoma expressing BCL2.

Efficacy of a steroid nasal spray compared with an antihistamine nasal spray in the treatment of perennial allergic rhinitis.

Allergic rhinitis is a common disease with a lifetime prevalence of 20% among the United States population. The cost of medication alone to manage allergic rhinitis in the United States was estimated to be $3.1 billion.

Expression and function of sialoadhesin in rat alveolar macrophages.

Alveolar macrophages (Amφ) represent an immunologically distinct sub-population within the reticuloendothelial system. Phagocytosis and possibly antigen presentation by Amφ are essential components of specific and innate primary immune defence processes against inhaled material. The mφ-restricted sheep erythrocyte receptor sialoadhesin (Sn) is a member of the immunglobulin superfamily and binds specifically to sialic acid-containing structures such as selectins and was originally identified as the sheep erythrocyte receptor (SER) responsible for sialic acid-dependent binding of native sheep erythrocytes (SE) to resident murine bone marrow macrophages in rosetting assays.

The ETV6-NTRK3 gene fusion encodes a chimeric protein tyrosine kinase that transforms NIH3T3 cells.

The congenital fibrosarcoma t(12;15)(p13;q25) rearrangement splices the ETV6 (TEL) gene on chromosome 12p13 in frame with the NTRK3 (TRKC) neurotrophin-3 receptor gene on chromosome 15q25. Resultant ETV6-NTRK3 fusion transcripts encode the helix - loop - helix (HLH) dimerization domain of ETV6 fused to the protein tyrosine kinase (PTK) domain of NTRK3. We show here that ETV6-NTRK3 homodimerizes and is capable of forming heterodimers with wild-type ETV6.