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Biomedical subjects

D Goldenberg

Publications and source records attributed to D Goldenberg.

At least 19 recordsLinked to original sources
PubMed2001

The RUNX3 gene--sequence, structure and regulated expression.

The RUNX3 gene belongs to the runt domain family of transcription factors that act as master regulators of gene expression in major developmental pathways. In mammals the family includes three genes, RUNX1, RUNX2 and RUNX3. Here, we describe a comparative analysis of the human chromosome 1p36.1 encoded RUNX3 and mouse chromosome 4 encoded Runx3 genomic regions. The analysis revealed high similarities between the two genes in the overall size and organization and showed that RUNX3/Runx3 is the smallest in the family, but nevertheless exhibits all the structural elements characterizing the RUNX family. It also revealed that RUNX3/Runx3 bears a high content of the ancient mammalian repeat MIR. Together, these data delineate RUNX3/Runx3 as the evolutionary founder of the mammalian RUNX family. Detailed sequence analysis placed the two genes at a GC-rich H3 isochore with a sharp transition of GC content between the gene sequence and the downstream intergenic region. Two large conserved CpG islands were found within both genes, one around exon 2 and the other at the beginning of exon 6. RUNX1, RUNX2 and RUNX3 gene products bind to the same DNA motif, hence their temporal and spatial expression during development should be tightly regulated. Structure/function analysis showed that two promoter regions, designated P1 and P2, regulate RUNX3 expression in a cell type-specific manner. Transfection experiments demonstrated that both promoters were highly active in the GM1500 B-cell line, which endogenously expresses RUNX3, but were inactive in the K562 myeloid cell line, which does not express RUNX3.

Alternative Splicing↗
PubMed2001

Acute mastoiditis--the antibiotic era: a multicenter study.

OBJECTIVES: To evaluate the clinical course and identify the causative organisms of acute mastoiditis in a community where most of the patients who develop acute otitis media are treated with antibiotics. METHODS: A multicenter retrospective review of a series of 223 consecutive cases of acute mastoiditis. SETTING: Nine secondary or tertiary academic or non-academic referral centers. RESULTS: Prior to the diagnosis of acute mastoiditis, 121 of the patients (54.3%) had been receiving oral antibiotic treatment for acute otitis media for periods ranging from 1 to 21 days (mean 5.3 days). Samples for bacterial culture were obtained from 152 patients. Cultures were negative in 60 patients. The organisms isolated in the 92 positive cultures were: Streptococcus pneumoniae (15 patients), Streptococcus pyogenes (14 patients), Staphylococcus aureus (13 patients), Staphylococcus coagulase negative (three patients), Pseudomonas aeruginosa (eight patients), Haemophilus influenzae (four patients), Proteus mirabilis (two patients), Escherichia coli (two patients), Klebsiella pneumoniae (one patient), Enterobacter (one patient), Acinetobacter (one patient), anaerobic gram-negative bacilli (one patient), and fungi (two patients). Ten patients had mixed flora. Sixteen patients presented with complications (cerebellar abscess, perisinus empyema, subdural abscess or empyema, extradural abscess, cavernous sinus thrombosis, lateral sinus thrombosis, bacterial meningitis, labyrinthitis, petrositis, or facial nerve palsy). CONCLUSIONS: Antibiotic treatment cannot be considered an absolute safeguard against the development of acute mastoiditis. Early myringotomy for acute otitis media seems to decrease the incidence of complications. The distribution of causative organisms in acute mastoiditis differs from that in acute otitis media. Intracranial complications in acute mastoiditis are not rare. Because of the diversity of causative organisms in acute mastoiditis and the growing resistance of bacteria to the various antibiotics, all means to obtain a sample for culture prior to antibiotic treatment, including general anesthesia.

Acute Disease↗
PubMed2001

What is chronic fatigue syndrome? Heterogeneity within an international multicentre study.

OBJECTIVE: We sought to compare the characteristics of patients presenting with chronic fatigue (CF) and related syndromes in eight international centres and to subclassify these subjects based on symptom profiles. The validity of the subclasses was then tested against clinical data. METHOD: Subjects with a clinical diagnosis of CF completed a 119-item self-report questionnaire to provide clinical symptom data and other information such as illness course and functional impairment. Subclasses were generated using a principal components-like analysis followed by latent profile analysis (LPA). RESULTS: 744 subjects returned complete data sets (mean age 40.8 years, mean length of illness 7.9 years, female to male ratio 3:1). Overall, the subjects had a high rate of reporting typical CF symptoms (fatigue, neuropsychological dysfunction, sleep disturbance). Using LPA, two subclasses were generated. Class one (68% sample) was characterized by: younger age, lower female to male ratio; shorter episode duration; less premorbid, current and familial psychiatric morbidity; and, less functional disability. Class two subjects (32%) had features more consistent with a somatoform illness. There was substantial variation in subclass prevalences between the study centres (Class two range 6-48%). CONCLUSIONS: Criteria-based approaches to the diagnosis of CF and related syndromes do not select a homogeneous patient group. While substratification of patients is essential for further aetiological and treatment research, the basis for allocating such subcategories remains controversial.

Adult↗
PubMed2001

Malignant tumors of the nose and paranasal sinuses: a retrospective review of 291 cases.

Malignant neoplasms of the nose and paranasal sinuses are not common among the general population. We present a retrospective study of 291 cases of malignant tumors of the nose and paranasal sinuses that were diagnosed in a northern Romanian population over a period of 35 years. We review the etiology, diagnosis, prognosis, and treatment of these tumors.

Adolescent↗
PubMed2000

Carcinoma of the dorsum of the tongue.

BACKGROUND: Squamous cell carcinoma (SCC) of the anterior two thirds of the tongue is the second most common oral cancer, with the lateral border being the most common location. Squamous cell carcinoma of the dorsum of the tongue is exceedingly rare and has been described in the past as a myth or misdiagnosis. The clinical diagnosis of SCC on the dorsum of the tongue is difficult because it may be mimicked by a wide variety of benign and premalignant lesions, including granular cell myoblastoma, erosive lichen planus, medial rhomboid glossitis, and amyloidosis. In this study we re-evaluate the entity of SCC of the dorsum of the tongue. METHODS: We reviewed 5 large series of carcinoma of the tongue, which include accurate documentation of the topographic location of the carcinoma. We also describe 5 cases of SCC of the dorsum of the tongue from our own series of 99 patients with carcinoma of the tongue. RESULTS: In all 6 series, carcinoma of the dorsum of the tongue was present in 3 to 5% of the carcinomas of the tongue. CONCLUSION: Although rare, SCC of the dorsum of the tongue exists and may be mimicked by benign conditions, thus SCC should be suspected when diagnosing lesions of this area of the tongue.

Adult↗
PubMed2000

Plastipore implants in the surgical treatment of atrophic rhinitis: technique and results.

BACKGROUND: Atrophic rhinitis is a distressing and socially crippling disease. Surgical treatment has been used for patients with severe disease that is unresponsive to medical therapy. METHODS: Eight patients with primary atrophic rhinitis were treated surgically by narrowing of the nasal fossae with implantation of 2 Plastipore plates per affected side into submucosal pockets into the floor of the nose and septum, thus reducing the volume of the nasal fossae. RESULTS: Excellent results were obtained in 6 patients, with complete resolution of symptoms and good results and only minor crusting in 2 patients. One implant was extruded spontaneously 18 months after implantation and was reimplanted. Results in this patient before and after reimplantation were excellent. There were no cases of infection and no other complications. CONCLUSION: We implanted Plastipore, a high-density polyethylene sponge with micropores, which enables tissue ingrowth, anchoring the implants to the surrounding tissue. The surgical technique is performed with the patient under local anesthesia and is relatively easy and avoids complicated flap procedures, allogeneic bone harvesting, and the discomfort of nostril closure for prolonged periods.

Adult↗
PubMed2000

Tracheotomy complications: a retrospective study of 1130 cases.

BACKGROUND: Tracheotomy is one of the most frequently performed surgical procedures in the critically ill patient. It is frequently performed as an elective therapeutic procedure and only rarely as an emergency procedure. Complications occur in 5% to 40% of tracheotomies depending on study design, patient follow-up, and the definition of the different complications. The mortality rate of tracheotomy is less than 2%. Numerous studies demonstrate a greater complication and mortality rate in emergency situations, in severely ill patients, and in small children. METHODS: A retrospective study of 1130 consecutive tracheotomies performed during 1 decade (January 1987 through December 1996) is presented. We studied the indications for surgery, the major complications of tracheotomy, and their treatment and outcome. We also noted the overall mortality rate and the specific complications that led to these deaths. RESULTS: In total, 1130 tracheotomies were performed. Major complications occurred in 49 of the cases, and 8 deaths were directly attributed to the tracheotomy. The most common complication was tracheal stenosis, which occurred in 21 cases. Hemorrhage was the second most common complication, which occurred in 9 cases. CONCLUSION: This is one of the largest series of consecutive tracheotomies compiled. We found a relatively low overall complication and mortality rate compared with other large series. Tracheal stenosis was the most common complication in contrast to other series. Our opinion is that this may reflect tracheal damage originally caused by prolonged intubation before the tracheotomy. We believe that all other complications of tracheotomy may be prevented or minimized by careful surgical technique and postoperative tracheotomy care.

Female↗
PubMed2000

Transcription-coupled translation control of AML1/RUNX1 is mediated by cap- and internal ribosome entry site-dependent mechanisms.

AML1/RUNX1 belongs to the runt domain transcription factors that are important regulators of hematopoiesis and osteogenesis. Expression of AML1 is regulated at the level of transcription by two promoters, distal (D) and proximal (P), that give rise to mRNAs bearing two distinct 5' untranslated regions (5'UTRs) (D-UTR and P-UTR). Here we show that these 5'UTRs act as translation regulators in vivo. AML1 mRNAs bearing the uncommonly long (1,631-bp) P-UTR are poorly translated, whereas those with the shorter (452-bp) D-UTR are readily translated. The low translational efficiency of the P-UTR is attributed to its length and the cis-acting elements along it. Transfections and in vitro assays with bicistronic constructs demonstrate that the D-UTR mediates cap-dependent translation whereas the P-UTR mediates cap-independent translation and contains a functional internal ribosome entry site (IRES). The IRES-containing bicistronic constructs are more active in hematopoietic cell lines that normally express the P-UTR-containing mRNAs. Furthermore, we show that the IRES-dependent translation increases during megakaryocytic differentiation but not during erythroid differentiation, of K562 cells. These results strongly suggest that the function of the P-UTR IRES-dependent translation in vivo is to tightly regulate the translation of AML1 mRNAs. The data show that AML1 expression is regulated through usage of alternative promoters coupled with IRES-mediated translation control. This IRES-mediated translation regulation adds an important new dimension to the fine-tuned control of AML1 expression.

5' Untranslated Regions↗
PubMed2000

Laser partial epiglottidectomy as a treatment for obstructive sleep apnea and laryngomalacia.

Obstructive sleep apnea (OSA) and laryngomalacia are two different entities. Occasionally, they may have a common etiology: an elongated, flaccid, and lax epiglottis that is displaced posteriorly during inspiration causing airway obstruction. Twenty-seven adults with a diagnosis of airway obstruction or OSA of various degrees, and 12 infants with severe stridor associated with frequent apneas due to laryngomalacia, who on fiberoptic examination were found to have a posteriorly displaced epiglottis, underwent partial epiglottidectomy with a CO2 laser. Their postoperative recovery was uneventful. Polysomnographic studies performed after operation in the adult patients demonstrated statistically significant improvement in 85% of the patients. In all the cases of laryngomalacia, stridor ceased permanently after surgery, together with complete cessation of the apneic episodes. This study demonstrates that similar pathophysiological mechanisms may be involved in both laryngomalacia and in OSA. Effective and relatively safe treatment can be achieved by partial resection of the epiglottis with a microlaryngoscopic CO2 laser.

Adult↗
PubMed2000

Misplaced parotid glands: bilateral agenesis of parotid glands associated with bilateral accessory parotid tissue.

Agenesis of the parotid is a rare entity. It is usually unilateral but bilateral cases have been described as a rare cause of xerostomia. Accessory parotid tissue is also uncommon and is not normally associated with aplasia of the parotid gland. The embryological, histological, clinical and radiological findings of these two entities will be discussed in addition to the report of an obscure case of bilateral parotid agenesis together with bilateral accessory parotid tissue.

Child↗
PubMed2000

Phase I/II trial of multiple dose 131Iodine-MAb LL2 (CD22) in patients with recurrent non-Hodgkin's lymphoma.

The purpose of this to evaluate in a phase I/II study the efficacy and toxicity of a multi-dose administration of 131I labeled CD22 monoclonal antibody (131I-MAb-LL2) in escalating dose cohorts administered to relapsed non-Hodgkin's lymphoma (NHL) patients. Twenty-one patients with relapsed NHL received one of four dose levels of 131-MAb-LL2 administered in a twice weekly pattern. Starting with dose level 2, the patients also received 20 mg of unlabeled LL2 prior to each radiolabeled dose administered. Previously stored autologous peripheral blood progenitors were reinfused in case of prolonged cytopenias. Patients could repeat the same treatment if they had stable disease or a response to the first therapy at 8 weeks, and had not received their peripheral blood progenitors with the first cycle. Combining all of the dose cohorts, there were 5 complete responses or complete responses (undetermined) and 2 partial responses for a total response rate of 7/21 (33%). There was no dose response effect with responses documented at all dose levels. Expected toxicities were hematopoietic, requiring stem cell re-infusion in 5 patients. Other toxicities included hypothyroidism in 3 patients, and human anti-mouse antibody formation (HAMA) in 4 patients. In conclusion, 131I-MAb-LL2, when administered in a multi-dose fashion with 20 mg unlabeled antibody pre-dosing, resulted in a response rate of 33% in heavily pre-treated NHL patients. Non-hematologic toxicities were mild and few in number. Further evaluation of this treatment is warranted and further dose escalation will be possible.

Adolescent↗
PubMed2000

Submucosal arytenoidectomy: new surgical technique and review of the literature.

OBJECTIVE: Arytenoidectomy is indicated in cases of bilateral median vocal cord paralysis (most commonly due to recurrent laryngeal nerve paralysis), ankylosis of the cricoarytenoid joint due to arthritis, and tumours of the arytenoid cartilage. We propose the use of the submucosal approach, to excise the arytenoid cartilage in cases of vocal cord paralysis. We present the surgical technique and review the history and relevant literature, as well as the pros and cons of various surgical techniques for arytenoidectomy. SETTING: Department of Otolaryngology-Head and Neck Surgery, Rambam Medical Center, Haifa, Israel. METHOD: We present six cases: five cases of bilateral vocal cord paralysis and one case of a chondroma of the arytenoid with mechanical fixation of the cord. All patients suffered from dyspnea on mild exertion. An arytenoidectomy using the submucosal approach was performed on all six patients. RESULTS: Airway results were evaluated via fibre-optic videotape laryngoscopy and direct microlaryngoscopy. Voice was evaluated subjectively by the patients and by a speech therapist before and after surgery. Following the surgery, all six patients showed clinical improvement, they no longer suffered from dyspnea at rest or upon mild exertion, and they retained reasonable voice quality. CONCLUSION: The submucosal approach is not difficult to perform and preserves an intact laryngeal mucosa, which prevents the formation of granulation tissue and scarring, which may further obstruct the lumen. The resulting airway is good, with minimal compromise of phonation. We feel that the submucosal approach to arytenoidectomy is an important addition to the arsenal of many surgical techniques for the treatment of bilateral vocal cord paralysis.

Adolescent↗