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Biomedical subjects

B Hoffman

Publications and source records attributed to B Hoffman.

At least 37 records · Page 2Linked to original sources
PubMed2000

The role of taurine for cellular volume regulation of the hippocampus

Taurine is used for volume regulation in a number of cultured cells, including neurons and glia. OBJECTIVE: To evaluate the role of this amino acid in brain volume regulation in situ. METHODS: Hippocampi of adult Sprague-Dawley rats were cut into 400 &mgr;m slices and equilibrated for 2 hr at room temperature in artificial cerebrospinal fluid (aCSF) bubbled with 95% O(2)/5% CO(2). Slices then were perfused with aCSF at 36 degrees C and optically imaged. After 1 hr in isotonic aCSF (290 mOsm), slices were perfused with hypoosmotic aCSF (200 mOsm) made by reducing the concentration of NaCl. Images of transmitted light intensity were captured every 60 sec to assess intracellular volume. For some slices, 1 mM taurine was added to aCSF during room temperature equilibration and during the first 30 min at 36 degrees C to replace that lost during slice preparation. Taurine contents were measured in perchlorate extracts by HPLC. Data were analyzed by Student's t-tests. RESULTS: Taurine contents of slices incubated in isotonic aCSF with and without taurine were 97 +/- 1 and 26 +/- 2 nmol/(mg protein), respectively. The intensity of transmitted light through the CA1 region increased similarly during the first 20 min in hypoosmotic aCSF, regardless of taurine treatment. However, after 60 min of hypoosmotic exposure, light transmittance recovered more in taurine-treated slices (44 +/- 6%) than in untreated slices (28 +/- 3%, p <0.05). The hypoosmotic-induced transmittance increase was smaller in the CA3 region for both groups of slices; however, similar effects of taurine treatment were obtained for subsequent transmittance recovery. CONCLUSIONS: Sufficient levels of taurine are required for effective volume regulation of hippocampal slices.

Journal Article↗
PubMed1999

Interleukin-6 and leukemia inhibitory factor induction of JunB is regulated by distinct cell type-specific cis-acting elements.

Interleukin (IL)-6 plays an important role in a wide range of biological activities, including differentiation of murine M1 myeloid leukemic cells into mature macrophages. At the onset of M1 differentiation, a set of myeloid differentiation primary response (MyD) genes are induced, including the proto-oncogene for JunB. In order to examine the molecular nature of the mechanisms by which IL-6 activates the immediate early expression of MyD genes, JunB was used as a paradigm. A novel IL-6 response element, -65/-52 IL-6RE, to which a 100-kDa protein complex is bound, has been identified on the JunB promoter. Leukemia inhibitory factor (LIF)-induced activation of JunB in M1 cells was also mediated via the -65/-52 IL-6RE. The STAT3 and CRE-like binding sites of the JunB promoter, identified as IL-6-responsive elements in HepG2 liver cells were found, however, to play no role in JunB inducibility by IL-6 in M1 myeloid cells. Conversely, the -65/-52 IL-6RE is shown not to be necessary for JunB inducibility by IL-6 or LIF in liver cells. It appears, therefore, that immediate early activation of JunB is regulated differently in M1 myeloid cells than in HepG2 liver cells. This indicates that distinct cis-acting control elements participate in cell type-specific induction of JunB by members of the IL-6 cytokine superfamily.

Animals↗
PubMed1999

CR6: A third member in the MyD118 and Gadd45 gene family which functions in negative growth control.

MyD118 and Gadd45 are two related genes which encode for proteins that play important roles in negative growth control, including both growth suppression and apoptosis. A strategy was employed to clone new members of the MyD118 and Gadd45 family of genes. Based on alignment of the deduced amino acid sequences, one cDNA clone was found to encode for the murine homologue of human CR6, originally cloned as an IL-2 immediate-early response gene. The murine and human CR6 proteins were observed to be 97% identical, indicating that CR6 is an evolutionarily conserved protein. Analysis of CR6 expression during hematopoietic cell development associated with growth arrest and apoptotic cell death, upon exposure of hematopoietic cells to a variety of growth arrest and apoptotic stimuli, and in a variety of murine tissues, has revealed that CR6 expression differs significantly from the expression of the related MyD118 and Gadd45 genes. Nevertheless, CR6, like MyD118 and Gadd45, suppressed colony formation of human lung carcinoma H1299 cells. These data suggest that CR6 plays similar, but not identical, roles to MyD118 and Gadd45 in negative control of cell growth.

Amino Acid Sequence↗
PubMed1999

Quantitative structure-activity relationship modeling of dopamine D(1) antagonists using comparative molecular field analysis, genetic algorithms-partial least-squares, and K nearest neighbor methods.

Several quantitative structure-activity relationship (QSAR) methods were applied to 29 chemically diverse D(1) dopamine antagonists. In addition to conventional 3D comparative molecular field analysis (CoMFA), cross-validated R(2) guided region selection (q(2)-GRS) CoMFA (see ref 1) was employed, as were two novel variable selection QSAR methods recently developed in one of our laboratories. These latter methods included genetic algorithm-partial least squares (GA-PLS) and K nearest neighbor (KNN) procedures (see refs 2-4), which utilize 2D topological descriptors of chemical structures. Each QSAR approach resulted in a highly predictive model, with cross-validated R(2) (q(2)) values of 0.57 for CoMFA, 0.54 for q(2)-GRS, 0.73 for GA-PLS, and 0.79 for KNN. The success of all of the QSAR methods indicates the presence of an intrinsic structure-activity relationship in this group of compounds and affords more robust design and prediction of biological activities of novel D(1) ligands.

Algorithms↗
PubMed1999

Prospective assessment of the utility of EUS in the evaluation of gallstone pancreatitis.

BACKGROUND: The ability to identify common bile duct stones by noninvasive means in patients with acute biliary pancreatitis is limited. The aim of this study was to prospectively evaluate the ability of endosonography (EUS) to identify cholelithiasis and choledocholithiasis and predict disease severity in patients with nonalcoholic pancreatitis. METHODS: EUS was performed immediately before endoscopic retrograde cholangiopancreatography (ERCP) by separate blinded examiners within 72 hours of admission. Gallbladder findings were compared between EUS and transabdominal ultrasonography (US). Using endoscopic extraction of a bile duct stone as the reference standard for choledocholithiasis, the diagnostic yield of EUS was compared with transabdominal US and ERCP. Features identified during endosonographic imaging of the pancreas were correlated with length of hospitalization. RESULTS: Thirty-six patients were studied. EUS and transabdominal US were concordant in their interpretation of gallbladder findings in 92% of patients. The sensitivity of transabdominal US, EUS, and ERCP for identifying choledocholithiasis was 50%, 91%, and 92% and the accuracy was 83%, 97%, and 89%, respectively. Length of hospital stay was longer in patients with peripancreatic fluid (9.2 vs. 5.7 days, p < 0.1) and shorter in patients with coarse echo texture (2.6 vs. 7.2 days, p < 0.05) demonstrated on EUS. CONCLUSIONS: EUS can reliably identify cholelithiasis and is more sensitive than transabdominal US in detecting choledocholithiasis in patients with biliary pancreatitis. EUS may be used early in the management of patients with acute pancreatitis to select those who would benefit from endoscopic stone extraction. The utility of EUS for predicting pancreatitis severity requires further investigation.

Abdomen↗
PubMed1999

Phenolic constituents, furans, and total antioxidant status of distilled spirits.

The concentrations of 11 phenols and 5 furans were measured in 12 categories of distilled spirits by HPLC methodology, together with the total antioxidant status (TAS) of the same beverages. Ellagic acid was the phenol present in highest concentration in all beverages. Moderate amounts of syringaldehyde, syringic acid, and gallic acid, as well as lesser amounts of vanillin and vanillic acid, were measurable in most samples of whiskey, brandy, and rum but were largely undetectable in gin, vodka, liqueurs, and miscellaneous spirits. 5-(Hydroxymethyl)furfural was the predominant furan in the former three beverages, notably cognac, with 2-furaldehyde the next highest, but these were undetectable in most of the latter beverages. Highest TAS values were given by armagnac, cognac, and bourbon whiskey, all three of which tended toward the highest concentrations of phenols. Negative TAS values were exhibited by rum, vodka, gin, and miscellaneous spirits in line with the low or undetectable phenol concentrations in these beverages. Wood aging is the most likely source of phenols and furans in distilled spirits. Those beverages exposed to this treatment contain significant antioxidant activity, which is between the ranges for white and red wines, with the potential to augment the antiatherosclerotic functions attributable to the ethanol that they contain.

Alcoholic Beverages↗
PubMed1999

Cost-efficacy of endoscopic ultrasonography with fine-needle aspiration vs. mediastinotomy in patients with lung cancer and suspected mediastinal adenopathy.

BACKGROUND AND STUDY AIMS: The use of endoscopic ultrasonography (EUS) guidance for fine-needle aspiration (FNA) of mediastinal lymph nodes has become an important aid in the staging of bronchogenic carcinoma. In many cases, it may be an alternative to mediastinoscopy/mediastinotomy (MED), but the cost-effectiveness of the two techniques has not been compared. The aim of this study was to apply a decision-analysis model to compare the cost-effectiveness of EUS and MED in the preoperative staging of patients with non-small-cell lung cancer. PATIENTS AND METHODS: A decision-analysis model was designed, taking as entry criteria lung cancer and abnormal mediastinal lymph nodes verified by computerized tomography (CT). Performance characteristics of MED and EUS were retrieved from the published literature, as were life expectancy data. Direct actual costs of the relevant procedures were retrieved from the billing system of our hospital. RESULTS: The cost per year of expected survival is US$ 1.729 with the EUS strategy, and US$ 2.411 with the MED strategy. The advantage conferred by EUS remains even when the negative predictive value of EUS is as low as 0.22. CONCLUSION: Because of its low cost and high yield, EUS-guided FNA is a cost-effective aid assessing mediastinal lymphadenopathy.

Biopsy, Needle↗
PubMed1999

[Percutaneous dilatational tracheostomy].

BACKGROUND: Tracheostomy provides a method for long-term ventilation in intensive care, which reduces the risk of necrotizing lesions of the pharyngeal and laryngeal mucosa. Since the introduction of the percutaneous dilatational tracheostomy, experienced physicians are able to perform bedside tracheostomies. This presentation reviews the complication rate and long-term outcome of percutaneous dilatational tracheostomy. PATIENTS AND METHOD: The method was applied in 57 patients following previous orotracheal intubation averaging 7.8 days (3 to 15 days). Underlying diseases were sepsis/SIRS in 29, stroke in 7, cerebral hypoxemia after cardiopulmonary resuscitation in 10, trauma in 7, prolonged weaning in 2, primary neurological diseases in 2. RESULTS: The following complications occurred during the procedure: 1 major and 7 minor bleedings. 2 subcutaneous emphysemas, 1 mediastinal emphysema following tracheal injury. No complication required surgical intervention. In the follow-up 17 patients (30%) died from their underlying disease, none from complications of the tracheostomy. After removed of the tracheal tube, in 39 patients the stoma closed spontaneously within 7 to 14 days. In 8 patients the tracheostoma persisted for more than 3 months, but no clinically relevant tracheal stenosis was found. CONCLUSION: Percutaneous dilatational tracheostomy is a safe procedure easy to perform in intensive care units. Bronchoscopic control is necessary to avoid complications.

Dilatation↗
PubMed1999

Cancer survivors' employment and insurance rights: a primer for oncologists.

Cancer survivors' access to equal employment opportunities and adequate health insurance has changed significantly during the 1990s. New federal and state laws have expanded survivors' rights to be treated fairly in the workplace, although some problems still exist. Survivors have experienced less progress, however, in obtaining and retaining adequate health insurance. This article reviews the problems faced by cancer survivors in securing and keeping adequate employment and health insurance.

Employment↗
PubMed1999

Pancreatic imaging.

Pancreatic cancer has traditionally been difficult to diagnose. There are now numerous diagnostic tests that can visualize these tumors early when they are small and determine which cases are the most likely to be unresectable. The principal tests, including spiral CT, MR imaging, endoscopic ultrasound, and laparoscopy, have advantages and disadvantages. The purpose of this article is to review each technique, and try to come up with a recommended approach to evaluating the patient with pancreatic malignancy.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1998

MyD genes in negative growth control.

Two interrelated cellular processes are invoked simultaneously upon induction of differentiation, the regulated progression of cells through successive stages of cell differentiation and growth inhibition which ultimately leads to growth arrest. In tissues with rapid cell turnover terminally differentiated cells undergo programmed cell death. Terminal differentiation, thus, represents one form of negative growth control. It was surmised that the molecular engine which drives the differentiation process forward requires induction of positive regulators of terminal cell differentiation, to be found among differentiation primary response genes, as well as suppression of negative regulators, which correspond to genes which control cellular growth. This line of thought has prompted the isolation of myeloid differentiation primary response (MyD) genes activated in the absence of de novo protein synthesis, upon IL-6 induced terminal differentiation of murine M1 myeloblastic leukemia cells, where the cells growth arrest and ultimately undergo programmed cell death. As delineated in this review many of the genes identified as MyD genes, including both known genes [IRF-1, (AP-1)Fos/Jun.EGR-1] and novel ones (MyD88, MyD116, MyD118), turned out to play a role in negative growth control, including growth suppression and apoptosis, in many cell types, of both hematopoietic and non hematopoietic origins.

Adaptor Proteins, Signal Transducing↗
PubMed1998

The proto-oncogene c-myc and apoptosis.

Deregulated expression of c-Myc not only promotes proliferation, but also can either induce or sensitize cells to apoptosis. Inappropriate expression of c-Myc under conditions which inhibit growth and down-regulate endogenous c-Myc expression, including serum deprivation and exposure to cytotoxic agents including the anticancer agents vinblastine, etoposide, Ara-C, and nocodazole, usually results in programmed cell death in many different cell types. Also, inappropriate Myc expression is associated with an apoptotic response elicited by induction of differentiation. The proapoptotic property of c-Myc requires an intact N-terminal transactivation domain and bHLHZip domain, as well as interaction with Max, thereby implicating c-Myc target genes in this apoptotic process. Although some target genes, namely cdc25A and ODC, have been shown to participate in Myc-mediated apoptosis, no target gene has yet been identified which is essential for this apoptotic response. It is possible that the response of cells inappropriately expressing c-Myc is due not only to the growth arrest signals per se, but also to signals elicited by specific growth inhibitors in the context of a particular biological setting. Also regulating the response of the cells is expression of other oncogenes and tumor suppressor genes, as well as paracrine and autocrine survival factors. Apoptosis associated with inappropriate Myc expression limits the tumorigenic effect of the c-myc proto-oncogene. Mechanisms which inhibit apoptosis should enhance or promote tumorigenesis.

Animals↗
PubMed1998

The zinc finger transcription factor Egr-1 activates macrophage differentiation in M1 myeloblastic leukemia cells.

We previously have shown that the zinc finger transcription factor Egr-1 blocked granulocytic differentiation of HL-60 cells, restricting differentiation along the monocytic lineage. Egr-1 also was observed to block granulocyte colony-stimulating factor (G-CSF)-induced differentiation of interleukin-3 (IL-3)-dependent 32Dcl3 hematopoietic precursor cells, endowing the cells with the ability to be induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) for terminal differentiation along the macrophage lineage. To better understand the function of Egr-1 as a positive modulator of monocytic differentiation, in this work we have studied the effect of ectopic expression of Egr-1 on the murine myeloblastic leukemic cell line M1, which is induced for differentiation by the physiological inducer IL-6. It is shown that, unlike in HL-60 and 32Dcl3 cells, ectopic expression of Egr-1 in M1 cells resulted in activation of the macrophage differentiation program in the absence of differentiation inducer. This included the appearance of morphologically differentiated cells, decreased growth rate in mass culture, and cloning efficiency in soft agar, and expression of endogenous c-myb and c-myc mRNAs was markedly downregulated. Untreated M1Egr-1 cells also exhibited cell adherence, expression of Fc and C3 receptors, and upregulation of the myeloid differentiation primary response genes c-Jun, junD, and junB and the late genetic markers ferritin light-chain and lysozyme. Ectopic expression of Egr-1 in M1 cells also dramatically increased the sensitivity of the cells for IL-6-induced differentiation, allowed a higher proportion of M1 cells to become terminally differentiated under conditions of optimal stimulation for differentiation, and decreased M1 leukemogenicity in vivo. These findings demonstrate that the functions of Egr-1 as a positive modulator of macrophage differentiation vary, depending on the state of lineage commitment for differentiation of the hematopoietic cell type.

Animals↗
PubMed1998

Defining the physician's duty to warn: consensus statement of Ontario's Medical Expert Panel on Duty to Inform.

Ontario's Medical Expert Panel on Duty to Inform was formed to consider the duty of Ontario physicians in circumstances where a patient threatens to kill or cause serious bodily harm to a third party. The panel was concerned about the implications of any duty to inform on the integrity of the physician-patient relationship, particularly with respect to confidentiality. The panel agreed that regulations safeguarding the confidentiality of patient information ought to be changed only if there is a critical reason for doing so, but, after deliberation, the panel members concluded that the need to protect the public from serious risk of harm is a paramount concern that should supersede the duty of confidentiality. The recommendations reported here were endorsed in principle by the panelists and the groups they represented (the Royal College of Physicians and Surgeons of Canada, the Canadian Medical Protective Association, the College of Physicians and Surgeons of Ontario, the Ontario College of Family Physicians and the Ontario Medical Association) and are being implemented by the College of Physicians and Surgeons of Ontario.

Advisory Committees↗
PubMed1998

Clinical implications of endoluminal ultrasonography using through-the-scope catheter probes.

BACKGROUND: Ultrasound catheter probe-assisted endosonography is a relatively new technique. The aim of this prospective multicenter study was to determine its potential clinical impact by assessing changes in diagnostic and therapeutic management affected by catheter probes compared with ultrasound endoscopes. METHODS: Endosonographers at three centers selected theoretic diagnostic and therapeutic plans that would be followed if neither catheter probes nor ultrasound endoscopes were available. Patients with suitable lesions underwent endosonography with catheter probes followed by an ultrasound endoscope. Diagnostic and therapeutic plans were noted after each examination. RESULTS: Sixty-six patients, of whom 15 had a stenotic esophageal cancer, 39 had a mucosal or submucosal lesion, and 12 had a stricture of the pancreaticobiliary system or the gastrointestinal tract, were enrolled. If neither form of endosonography were available, invasive or surgical diagnostic procedures would have been performed on 23 (35%) patients and surgical therapy would have been planned in 31 (47%) patients. Catheter probe-assisted ultrasonography and endoscopic ultrasonography led to a less invasive diagnostic plan in 11 (16%) and 12 (18%) patients and a less invasive therapeutic plan in 10 (15%) and 14 (21%) patients, respectively (p > 0.1 for differences). CONCLUSIONS: Catheter probe-assisted endosonography has a modest effect on diagnostic and therapeutic management, comparable with endoscopic ultrasonography in the same patients. The vast majority of effected changes are toward less invasive management.

Digestive System Neoplasms↗