An unusual neurological problem in a patient admitted for acute myocardial infarction.
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Adenoma, Acidophil↗
Biomedical subjects
J A Bell
Publications and source records attributed to J A Bell.
Prognostic significance of serum c-erbB-2 protein in breast cancer patients.
The tissue expression of c-erbB-2 protein in breast cancer is a marker of poor prognosis in a number of studies. More recently it has also been suggested that c-erbB-2 expression may predict response to systemic therapy in patients with advanced breast cancer. The measurement of c-erbB-2 protein in the serum of breast cancer patients has now been reported, but the significance of this finding is not clear. In this study an ELISA assay was used to measure c-erbB-2 in the sera of 23 normal controls, 46 benign breast disease patients, and 119 breast cancer patients. Elevated serum c-erbB-2 protein levels were detected in 13% (3/23) of normal controls, 15% (7/46) of benign disease patients, 15% (7/46) of Stage I/II patients, 26% (9/35) of Stage III patients, and 21% (8/38) of Stage IV patients. The tissue expression of the c-erbB-2 protein showed no association with detection of the serum c-erbB-2 protein (p = 0.31). In the 67 Stage III and IV patients who had assessable disease the presence of the c-erbB-2 protein in the serum bore no relationship to response to hormonal therapy (p = 0.71). Serum detection of the c-erbB-2 protein in Stage I/II patients predicted for a worsening of both survival outcome (p = 0.002) and disease free interval (p = 0.002). A worse outcome was also seen for the Stage III patients (p = 0.04) and Stage IV patients, although the latter did not reach statistical significance (p = 0.27). This study found that the presence of c-erbB-2 in the serum of breast cancer patients was of prognostic significance for all stages of disease.
Biomarkers, Tumor↗
Physical and genetic map of the mitochondrial genome of Cryphonectria parasitica Ep155.
In the chestnut-blight fungus, Cryphonectria parasitica, a cytoplasmically transmissible (infectious) form of hypovirulence is associated with mitochondrial DNA (mtDNA) mutations that cause respiratory deficiencies. To facilitate the characterization of such mutations, a restriction map including the probable location of 13 genes was constructed for a relatively well-characterized virulent strain of the fungus, Ep155. The physical map is based on the order of all fragments generated by cleavage of the mtDNA by the PstI restriction endonuclease and includes some of the cleavage sites for HindIII, EcoRI, and XbaI. It was constructed from hybridization patterns of cloned mtDNA fragments with Southern blots of mtDNA digested with the four restriction enzymes. On this map, the probable locations of genes commonly found in the mitochondrial genomes of ascomycetes were determined by low-stringency hybridization of cloned Neurospora crassa mitochondrial gene probes to Southern blots of C. parasitica mtDNA. The data indicate that the mtDNA of strain Ep155 is a circular molecule of approximately 157 kbp and ranks among the largest mitochondrial chromosomes observed so far in fungi. The mtDNAs of 11 different C. parasitica isolates range in size from 135 to 157 kbp and in relatedness from 68 to 100 percent, as estimated from restriction-fragment polymorphisms. In addition to the typical mtDNA, the mitochondria of some isolates of the fungus contain double-stranded DNA plasmids consisting of nucleotide sequences not represented in the mtDNA of Ep155.
Ascomycota↗
Interaction of ascorbic acid with the neurotoxic effects of NMDA and sodium nitroprusside.
We have previously shown that ascorbic acid (AA) protects cortical neurons in culture from the toxic effects of NMDA. In the present study, we examined the interactions of AA with toxicity produced by nitric oxide (NO) that is generated from the breakdown of sodium nitroprusside (SNP), and with NMDA toxicity measured 24 h later. AA enhanced SNP toxicity, but it reduced toxicity of NMDA. We propose that these data support a model wherein AA produces neuroprotection by an action at the NMDA receptor, and indirectly with respect to NO. This effect occurs probably by antagonizing Ca2+ influx starting the cascade of biochemical events that lead to the production of NO.
Animals↗
C-erbB-3 in human breast carcinoma: expression and relation to prognosis and established prognostic indicators.
A series of 346 patients with primary operable breast cancer and a series of 145 patients with advanced breast cancer were investigated for c-erbB-3 protein expression using the monoclonal antibody RTJ1. Formalin-fixed, paraffin-embedded tumour samples were stained using a standard immunochemical method and staining was assessed on a four-point scale. The study aimed to observe the expression of the c-erbB-3 protein and investigate any relationship between expression and established prognostic indicators and prognosis. In both the primary and advanced series breast tumour tissue was found to stain heterogeneously for c-erbB-3. The staining was observed to be predominantly cytoplasmic and the majority of tumours exhibited moderate positivity. However, 15% and 35% of cases in the primary operable and advanced series respectively displayed strong positive staining. No significant difference was found between the staining in the primary and advanced series. In the primary operable breast cancers, no significant associations were demonstrated with overall survival, disease-free interval, regional recurrence, the presence of distant metastases, age, menopausal status, oestrogen receptor status, histological grade, lymph node stage, vascular invasion and c-erbB-2 protein expression. However, a significant association was seen between the degree of c-erbB-3 immunoreactivity and both tumour size (P < 0.01) and tumour type prognostic group (P = 0.05). No overall association with local recurrence was seen when the four groups of c-erbB-3 expression were analysed (P = 0.12), but when those tumours showing no or weak staining were compared with those showing moderate and strong immunoreactivity it was seen that the latter were significantly more likely to develop local recurrence (P = 0.03). In the series of patients with advanced disease, no significant associations were demonstrated with survival, UICC criteria, age, menopausal status, oestrogen receptor status, histological grade, c-erbB-2 status or the presence of vascular invasion. In conclusion this study found variable expression of c-erbB-3 protein in human breast carcinoma and an association with some recognised prognostic factors in those patients with primary operable breast carcinoma. It seems, however, unlikely that c-erbB-3 protein expression will emerge as a powerful enough prognostic factor to be of value in clinical practice.
Adult↗
Absorption and disposition of ranitidine hydrochloride in rat and dog.
1. The pharmacokinetics of ranitidine were studied in the male beagle dog at a dose level of 50 mg (intravenous) or 5 mg/kg (oral). 2. After intravenous administration, Clp was moderate (10.4 ml/min/kg) with Clr accounting for approximately 30% of total clearance. Vdarea was 3.5 l/kg, resulting in a t1/2 of approximately 4 h. 3. After oral administration, F was good (73%) with peak plasma concentrations of ranitidine (2 micrograms/ml) achieved within 0.5-1 h hour after dosing. t1/2 (4.1 h) was similar to that observed after intravenous administration. 4. The absorption, metabolism and excretion of [14C]-ranitidine were studied in rat and dog after oral administration at a dose level of 50 mg/kg. 5. Urinary excretion was the major elimination pathway for radioactive drug-related material in both species (62-75% of the dose). Unchanged ranitidine was the major radioactive component in both rat and dog urine (0-24 h), accounting for approximately 40% of the dose in each case. 6. In dog, ranitidine undergoes N-oxidation (approximately 30% of dose) whereas in rat, N-oxidation, S-oxidation, N-demethylation and oxidative deamination are all evident, with each metabolite accounting for < 6% of the dose. 7. Two previously unreported metabolites of ranitidine were identified in rat urine using newly developed hplc and lc/ms methods. These metabolites result from single and di-N-demethylation of ranitidine and accounted for 4 and 1% of the dose respectively.
Absorption↗
History of the Medical Library Association's credentialing program.
Since the Medical Library Association (MLA) adopted the Code for the Training and Certification of Medical Librarians in 1949, MLA members have reviewed and revised the program regularly. This paper traces the history of MLA's professional recognition program to illustrate how the program has changed over time and to identify the issues that have surrounded it. These issues include the value of the program to individual members, cost to MLA, appropriate entry requirements, certification examinations, and recertification requirements. The development and operation of MLA's current credentialing program, the Academy of Health Information Professionals, is described in detail.
Academies and Institutes↗
MK-801 blocks the expression but not the development of tolerance to morphine in the isolated spinal cord of the neonatal rat.
This study investigated the role of (MK-801; [(+)-5-methyl-10,11-dihydro-5 H-dibenzo[a,d]-cyclo-hepten-5,10-imine hydrogen maleate) in the development and expression of tolerance to morphine in the isolated spinal cord of the neonatal rat. Neonatal rats were treated chronically (3 or 4 days) with either morphine, morphine + MK-801, MK-801 alone or saline. Morphine, in a concentration-dependent manner, depressed a delayed ventral root potential produced by supramaximal electrical stimulation of an ipsilateral dorsal root. Chronic treatment of neonates with morphine alone, morphine with MK-801 and MK-801 alone produced tolerance to morphine depression of the ventral root potential. Acute MK-801 (300 nM) did not depress the ventral root potential but enhanced the depressant effects of acute morphine on the ventral root potential in saline-treated controls. Acute MK-801 (300 nM) appeared to reverse tolerance in all of the drug-treated groups. We conclude that MK-801 can mask the expression of morphine tolerance by enhancing the acute depressant effects of morphine.
Analgesics, Opioid↗
Co-treatment with MK-801 potentiates naloxone-precipitated morphine withdrawal in the isolated spinal cord of the neonatal rat.
The effects of acute and chronic administration of (MK-801: [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate) were assessed on morphine dependence in the isolated spinal cord of the neonatal rat and on behavioral measures in intact adult rats. Neonatal rats were treated chronically (3 or 4 days) with injections of either morphine, morphine + MK-801, or saline. Naloxone (10 microM) which increased baseline ventral root spontaneous firing, induced more activity in spinal cords from morphine-treated neonates than in saline controls. In spinal cords from neonates receiving MK-801 with morphine, naloxone-induced spontaneous firing was significantly greater than in saline-treated and morphine alone-treated neonates. Acute MK-801 attenuated naloxone-induced firing in the morphine-treated group. Chronic co-treatment with MK-801 increased locomotor signs of withdrawal and decreased mastication in intact adult rats which had been treated chronically with morphine. MK-801-induced enhancement of morphine withdrawal is consistent with upregulation of NMDA receptors.
Animals↗
Systemic immunization with papillomavirus L1 protein completely prevents the development of viral mucosal papillomas.
Infection of mucosal epithelium by papillomaviruses is responsible for the induction of genital and oral warts and plays a critical role in the development of human cervical and oropharyngeal cancer. We have employed a canine model to develop a systemic vaccine that completely protects against experimentally induced oral mucosal papillomas. The major capsid protein, L1, of canine oral papillomavirus (COPV) was expressed in Sf9 insect cells in native conformation. L1 protein, which self-assembled into virus-like particles, was purified on CsCl gradients and injected intradermally into the foot pad of beagles. Vaccinated animals developed circulating antibodies against COPV and became completely resistant to experimental challenge with COPV. Successful immunization was strictly dependent upon native L1 protein conformation and L1 type. Partial protection was achieved with as little as 0.125 ng of L1 protein, and adjuvants appeared useful for prolonging the host immune response. Serum immunoglobulins passively transferred from COPV L1-immunized beagles to naive beagles conferred protection from experimental infection with COPV. Our results indicate the feasibility of developing a human vaccine to prevent mucosal papillomas, which can progress to malignancy.
Animals↗
A cytoplasmically transmissible hypovirulence phenotype associated with mitochondrial DNA mutations in the chestnut blight fungus Cryphonectria parasitica.
Mutations causing mitochondrial defects were induced in a virulent strain of the chestnut blight fungus Cryphonectria parasitica (Murr.) Barr. Virulence on apples and chestnut trees was reduced in four of six extensively characterized mutants. Relative to the virulent progenitor, the attenuated mutants had reduced growth rates, abnormal colony morphologies, and few asexual spores, and they resembled virus-infected strains. The respiratory defects and attenuated virulence phenotypes (hypovirulence) were transmitted from two mutants to a virulent strain by hyphal contact. The infectious transmission of hypovirulence occurred independently of the transfer of nuclei, did not involve a virus, and dynamically reflects fungal diseases caused by mitochondrial mutations. In these mutants, mitochondrial mutations are further implicated in generation of the attenuated state by (i) uniparental (maternal) inheritance of the trait, (ii) presence of high levels of cyanide-insensitive mitochondrial alternative oxidase activity, (iii) cytochrome deficiencies, and (iv) structural abnormalities in the mtDNA. Hence, cytoplasmically transmissible hypovirulence phenotypes found in virus-free strains of C. parasitica from recovering trees may be caused by mutant forms of mtDNA.
Journal Article↗
Evaluation of urinary cortisol:creatinine ratios for the diagnosis of hyperadrenocorticism associated with adrenal gland tumors in ferrets.
Assays were validated for the measurement of urinary concentrations of cortisol and creatinine in domestic ferrets (Mustela putorius furo). Urinary concentrations of cortisol and creatinine and the calculated urinary cortisol:creatinine ratio (UCCR) values were determined for 29 clinically normal female ferrets, 22 clinically normal male ferrets, and 12 ferrets with adrenal gland tumors. The UCCR values for the 51 clinically normal ferrets ranged from 0.04 x 10(-6) to 1.66 x 10(-6), with a median value of 0.22 x 10(-6). The UCCR values were significantly (P < or = 0.01) higher in the 12 ferrets with adrenal tumors, with a range of 0.5 x 10(-6) to 60.13 x 10(-6) and a median of 5.98 x 10(-6). We concluded that determination of UCCR values was useful in the diagnosis of hyperadrenocorticism associated with adrenal neoplasia in domestic ferrets.
Adenocarcinoma↗
An evaluation of the cell cycle-associated monoclonal antibody Ki-S1 as a prognostic factor in primary invasive adenocarcinoma of the breast.
Immunohistochemical staining with the novel monoclonal antibody Ki-S1, believed to recognize a cell cycle-associated antigen, was investigated in 110 cases of invasive carcinoma of the breast. Immunoreactivity indices were compared with disease-free interval (DFI), overall survival, and a series of other prognostic indicators. Significant positive correlations were found between the percentage of strongly positive immunoreactive nuclei and tumour size, histological grade and type, vascular invasion, and mitotic count. A significant negative correlation was found with age. No significant correlation was found with either DFI or overall survival. Although a correlation with mitotic count does imply that the Ki-S1 antigen is cell cycle-associated to some extent, Ki-S1 does not appear to be a useful prognostic factor in human breast carcinoma.
Adenocarcinoma↗
Prenatal analysis of the insulin receptor gene in a family with leprechaunism.
We report on the prenatal diagnosis of a fetus at risk of leprechaunism. We had previously determined the nature of the causative mutation in the insulin receptor gene in this family. The mutation removes a restriction site for the enzyme Mbo II. Genomic DNA was extracted from a chorionic villus sample and the 3' half of exon 2 was amplified by the polymerase chain reaction (PCR) followed by restriction digest. Using this method, we correctly predicted an unaffected child.
Chorionic Villi↗
A high-resolution map of the brown (b, Tyrp1) deletion complex of mouse chromosome 4.
For over 40 years germ-cell mutagenesis experiments have generated many new mutations at the brown (b or Tyrp1) locus on mouse Chromosome (Chr) 4. These mutations, many of which are deletions, were recovered by the specific-locus mutagenesis technique. Previous analysis of a panel of brown deletions, generated at Oak Ridge, has enabled both a preliminary molecular and a functional map around the locus to be generated. We have used a panel of hybrid DNA from 25 Oak Ridge deletions, where the deleted chromosome was heterozygous with a Mus spretus chromosome, to map polymorphic markers including microclones, microsatellites, and cloned DNA markers. We have generated a fine structure map, based on 25 new markers, of an 8.5-cM region surrounding the brown locus. This map will prove useful in future mapping studies of this region and in the isolation of the genes that lie within it.
Animals↗
Cathepsin D in primary breast carcinoma: adverse prognosis is associated with expression of cathepsin D in stromal cells.
The immunohistochemical expression of the aspartyl protease enzyme cathepsin D was examined in a consecutive series of 103 primary operable breast carcinomas with the polyclonal antibody NCL-CDp. Expression of cathepsin D was identified within the epithelial and stromal components of all tumours examined. No significant associations of increased cathepsin D expression in the epithelial tumour component with conventional prognostic indices such as tumour size, grade, lymph node stage, or patient survival were identified. However, significant associations of increased stromal cathepsin D expression and high tumour grade, chi 2 = 11.40 (df = 2), p = 0.003; increased tendency to local recurrence, chi 2 = 6.87 (df = 1), p = 0.009; regional recurrence, chi 2 = 7.44 (df = 1), p = 0.006; poorer disease free survival, chi 2 = 14.9 (df = 1), p = 0.0001; and poorer overall patient survival, chi 2 = 6.90 (df = 1), p = 0.0086, were identified. Cathepsin D expression is present in all breast tumours. Stromal cathepsin D expression is a neglected immunohistochemical prognostic parameter which could explain some of the previous apparently conflicting reports concerning the effect on patient prognosis of biochemical (i.e. total) and immunohistochemical estimations of cathepsin D in breast cancers.
Breast Neoplasms↗
Assessment of angiogenesis in breast carcinoma: an important factor in prognosis?
Recent evidence suggests that angiogenesis, as assessed by vascular density, may be an independent prognostic factor in breast carcinoma. The authors chose to examine this hypothesis further using two different methods, both using an immunohistochemical technique to assess vascularity. In the first, tissue sections from 93 patients with human breast carcinoma were immunostained for the endothelial antigen CD 34. Fields were selected at random in sections stained with the monoclonal antibody QBEnd/10, and both the number of blood vessels and percentage of endothelial cells per unit area measured using an interactive image analysis system (SEESCAN). In the second, an additional 72 patients were added and the 165 sections immunostained for CD31 (PECAM 1) using the monoclonal antibody JC 709. The area of highest vascular density was then identified and measured. A statistically significant correlation was found between percentage endothelial area and tumor type (P < .03) using the first method, and, for lymph node-negative patients only, between vascular density and tumor type (P < .02) using the second method. There was no correlation with lymph node status, recurrence, distant metastases, or overall survival using either method (minimum follow-up 12 years). The authors conclude that the evaluation of tumor angiogenesis using these methods does not provide additional prognostic information in this group of patients.
Antibodies, Monoclonal↗
A comparison of clinical index and ejection fractions in predicting cardiac complications following infrarenal aortic reconstruction.
OBJECTIVE: To compare the Detsky clinical cardiac risk index with ejection fraction measurements in predicting postoperative cardiac events. DESIGN: Prospective study. SETTING: District General Hospital. MATERIALS: 48 patients undergoing infrarenal aortic reconstruction. CHIEF OUTCOME MEASURES: Ejection fractions were measured both by echocardiography and a technetium 99 MUGA scan. MAIN RESULTS: Three patients developed four major cardiac events (LVF three, fatal myocardial infarction one). Fourteen patients experienced 15 minor cardiac events (arrhythmia 11, ST segment depression four). The clinical index predicted postoperative cardiac problems (p = 0.0001). There was no correlation between ejection fraction measurement and postoperative cardiac events nor between ejection fraction measurements and the clinical index. Combining the index with ejection fraction measurement provided no additional information over the index alone. CONCLUSIONS: Calculation of a clinical index before aortic reconstruction is a simple and reliable way of selecting patients who are at risk of developing postoperative cardiac events.
Adult↗