tbuckley/cabot-search huggingface dataset:
Herceptin-Geldanamycin Immunoconjugates
Authors: Raya Mandler, Hisataka Kobayashi, Ella R. Hinson, Martin W. Brechbiel, Thomas A. Waldmann
Journal: Cancer Research (2004)

Abstract The efficacy of monoclonal antibodies (mAbs) as single agents in targeted cancer therapy has proven to be limited. Arming mAbs with a potent toxic drug could enhance their activity. Here we report that conjugating geldanamycin (GA) to the anti-HER2 mAb Herceptin improved the activity of Herceptin. The IC50s of the immunoconjugate H-GA were 10–200-fold lower than that of Herceptin in antiproliferative assays, depending on the cell line. The H-GA mode of action involved HER2 degradation, which was partially lactacystin sensitive and thus proteasome dependent. The linkage between GA and Herceptin remained stable in the circulation, as suggested by the pharmacokinetics of Herceptin and conjugated GA, which were almost identical and significantly different from that of free GA. Tumor uptake of Herceptin and H-GA were similar (52 ± 7 and 43 ± 7% of the initial injected dose per gram tissue, respectively; P = 0.077), indicating no apparent damage attributable to conjugation. Therapy experiments in xenograft-bearing mice consisted of weekly i.p. doses, 4 mg/kg for 4 months. H-GA showed a greater antitumor effect than Herceptin because it induced tumor regression in 69% of the recipients compared with 7% by Herceptin alone. Median survival time was 145 days as opposed to 78 days, and 31% of the recipients remained tumor free 2 months after therapy was terminated versus 0% in the Herceptin group. Enhancement of Herceptin activity could be of significant clinical value. In addition, the chemical linkage and the considerations in therapeutic regimen described here could be applied to other immunoconjugates for targeted therapy of a broad spectrum of cancers.
Biochemical and morphological changes that characterise recovery from necrotising biliary pancreatitis in the opossum.
Authors: M Runzi, A Saluja, A Kaiser, D Gerdes, A Sengupta, M L Steer
Journal: Gut (1995)

The events that characterise recovery from severe biliary pancreatitis have not been defined. This study used a reversible model of necrotising pancreatitis, induced by obstructing the opossum common bile pancreatic duct (CBPD), to evaluate this phenomenon. The CBPD of opossums was obstructed with a balloon tipped catheter for five days and then decompressed by removal of the catheter. Recovery was evaluated 0-90 days after relief of obstruction. Serum bilirubin and amylase values rapidly declined, reaching control values 7-14 days after removal of the obstructing catheter. Pancreatic protein and amylase values were transiently increased shortly after relief of obstruction but returned to control values 21 days after decompression. Pancreatic ornithine decarboxylase activity and incorporation of [3H]-thymidine into DNA were transiently increased 14 days after duct decompression suggesting that regeneration occurs at approximately that time. Foci of pancreatic necrosis involved roughly 40% of the gland at time of decompression but these foci gradually disappeared and the gland resembled that of control animals 60 days after decompression. Evidence of fibrosis or collagen deposition in the pancreas was not noted at any time. These studies show that recovery after necrotising biliary pancreatitis occurs comparatively rapidly and the restitution ad integrum occurs. Recovery from necrotising acute pancreatitis in this model is not associated with the development of chronic pancreatitis.
A Prospective Study of Red and Processed Meat Intake in Relation to Cancer Risk
Authors: Amanda J Cross, Michael F Leitzmann, Mitchell H Gail, Albert R Hollenbeck, Arthur Schatzkin, Rashmi Sinha
Journal: PLoS Medicine (2007)

Red meat and processed meat have been associated with carcinogenesis at several anatomic sites, but no prospective study has examined meat intake in relation to a range of malignancies. We investigated whether red or processed meat intake increases cancer risk at a variety of sites.The National Institutes of Health (NIH)-AARP (formerly the American Association for Retired Persons) Diet and Health Study is a cohort of approximately 500,000 people aged 50-71 y at baseline (1995-1996). Meat intake was estimated from a food frequency questionnaire administered at baseline. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals within quintiles of red and processed meat intake. During up to 8.2 y of follow-up, 53,396 incident cancers were ascertained. Statistically significant elevated risks (ranging from 20% to 60%) were evident for esophageal, colorectal, liver, and lung cancer, comparing individuals in the highest with those in the lowest quintile of red meat intake. Furthermore, individuals in the highest quintile of processed meat intake had a 20% elevated risk for colorectal and a 16% elevated risk for lung cancer.Both red and processed meat intakes were positively associated with cancers of the colorectum and lung; furthermore, red meat intake was associated with an elevated risk for cancers of the esophagus and liver.
Different therapeutic responses to treadmill exercise of heart failure due to ischemia and infarction in rats
Authors: K YOSHINARI, H YAOITA, K MAEHARA, Y MARUYAMA
Journal: Cardiovascular Research (2004)

The effects of exercise, a therapeutic tool in ischemic heart disease (IHD), may differ in ischemic and infarcted hearts.To assess this, we created coronary stenosis (CS), which reduced coronary flow reserve (CFR), or coronary occlusion to induce myocardial infarction (MI) in rats, and subjected them to treadmill exercise for either 5 (5-min Ex) or 15 min/day (15-min Ex) for 12 weeks. Left ventricular (LV) diameters were increased and ejection fractions decreased by echocardiography, and myocardial nitric oxide (NO) activity, measured by the in vitro MVO2 method, was reduced in both CS and MI rats compared with the sham. In CS rats, myocardial wall thickening fractions were not affected at 5 min of exercise, whereas they were reduced at 15 min of exercise, suggesting exercise-induced ischemia. Despite no changes in CS severity, the 5-min Ex increased CFR, ameliorated myocardial NO activity, attenuated left ventricular (LV) dysfunction and remodeling, reduced serum brain natriuretic peptide (BNP) levels, and improved survival, whereas the 15-min Ex aggravated LV dysfunction and remodeling. In contrast, neither of the exercise protocols improved these parameters in MI rats.Therapeutic responses to exercise differed in ischemic and infarcted hearts, partly via circulatory modulation downstream of the epicardial CS in relation to exercise-induced ischemia. When employing exercise for IHD, the causes of IHD, as well as the exercise protocols, need to be considered to achieve optimal effects.
Basal vascular tone in the kidney. Evaluation from the static pressure-flow relationship under normal autoregulation and at maximal dilation in the dog.
Authors: R Gross, H Kirchheim, K Brandstetter
Journal: Circulation Research (1976)

In conscious dogs static pressure-flow relationships (I-P curves) were obtained both for the normal autoregulating kidney vasculature and under conditions of maximal vasodilation induced by infusion of papaverine or acetylcholine into the renal artery. Concentration-response curves for the substances infused showed the typical S-shape. Control I-P curves exhibited an autoregulatory plateau; under maximal vasodilation the I-P curves were pressure-passive up to a perfusion pressure of 50 mm Hg, following a power function (1 = a-Pn) with an exponent greater than 1. Under the influence of acetylcholine, renal blood flow was significantly higher than under control conditions even at a perfusion pressure of 20 mm Hg. This indicates that there is an appreciable vascular tone even at a low pressure. The I-P curves under acetylcholine showed a break at about 50 mm Hg, above which the I-P curves were straight lines.
Lack of association of increased antibody levels to mycobacterial hsp65 with rheumatoid arthritis: results from a study of disease discordant twin pairs.
Authors: J Worthington, A S Rigby, A J MacGregor, A J Silman, D Carthy, W E Ollier
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--To investigate the role of humoral immunity to mycobacterial hsp65 in the aetiology of rheumatoid arthritis. METHODS--Levels of IgG antibodies to recombinant mycobacterial hsp65 were measured by enzyme linked immunosorbent assay (ELISA) in serum samples of 152 twin pairs discordant for RA and in serum samples from 62 normal blood donors. RESULTS--No significant differences between antibody levels in the subjects with RA compared either with their unaffected twins or with a group of normal blood donors was observed. In the monozygotic twins there was a strong but negative association between levels of antibody to hsp65 and disease status. Zygosity, sex, and HLA status did not significantly affect levels of antibody to hsp65. CONCLUSION--Previous reports of an association between hsp65 and RA were not confirmed.
Leukemia risk following Hodgkin's disease: relation to cumulative dose of alkylating agents, treatment with teniposide combinations, number of episodes of chemotherapy, and bone marrow damage.
Authors: F E van Leeuwen, A M Chorus, A W van den Belt-Dusebout, A Hagenbeek, R Noyon, E H van Kerkhoff, H M Pinedo, R Somers
Journal: Journal of Clinical Oncology (1994)

PURPOSE The development of leukemia is one of the most serious long-term complications of modern treatment for Hodgkin's disease (HD). This study was undertaken to examine the relation between risk of leukemia and various treatment factors (including cumulative dose of cytostatic drugs and interaction with radiotherapy [RT]), while also assessing the effect of treatment-induced bone marrow damage. PATIENTS AND METHODS We conducted a case-control study in a cohort of 1,939 patients treated for HD between 1966 and 1986 in the Netherlands. Detailed information from the medical records was obtained for 44 cases of leukemia and 124 matched controls, in whom leukemia had not developed. RESULTS The cumulative dose of mechlorethamine was the most important factor in determining leukemia risk. As compared with patients who received RT alone, patients treated with six or fewer cycles of combinations including nitrogen mustard (mechlorethamine) and procarbazine had an eightfold increased risk of developing leukemia (P = .08), while patients who received more than six of such cycles had a greater than 40-fold excess risk (P &lt; .001). Treatment with lomustine or a combination of teniposide and cyclophosphamide also significantly increased the risk of leukemia. Patients who had received chemotherapy (CT) during two or more time periods had a nearly 40-fold increased risk of leukemia as compared with patients treated only once. The extent of RT did not further increase leukemia risk among patients who also received CT. A significantly increased risk of leukemia was found among patients with low platelet counts, both in response to initial therapy and during follow-up. Patients who experienced 2 or more half-year periods with platelet counts less than 75 x 10(6)/mL had an approximately fivefold risk of developing leukemia, and a similar risk increase was found for patients who responded to initial treatment with a &gt; or = 70% decrease of platelet counts (as compared with patients who had a &lt; or = 50% decrease). CONCLUSION In addition to mechlorethamine, lomustine and teniposide combinations were also linked to an elevated risk of developing leukemia. Since the number of CT episodes was found to be a strong determinant of leukemia risk, it is important that new therapies for HD continue to yield high initial cure rates. Further studies are warranted to investigate whether patients at high risk for developing leukemia may be identified from the response of their platelets to initial therapy for HD.
Acute Rheumatism: Five Cases of Apparently Direct Infection
Authors: E. S. Hawthorne
Journal: BMJ (1903)

APPARENT INFECTION IN ACUTE RHEUMATISM.[DEC.26j 1903.which often cause peripheral neuritis, and also other toxaemic diseases, such as typhoid fever, plague and acute rheumatism, which do not or rarely give rise to peripheral neuritis.3. Beri-beri and diphtheria are the diseases par excellence in which sudden fatal heart failure occurs.4. The heart-muscle degeneration is not a secondary result of neuritis of the vagus.5. The heart-muscle degeneration takes place as a rule before skeletal-muscle degeneration and is the result probably of direct action of the toxin and not a secondary result of nerve change.6. Sudden heart failure does not indicate a sudden lesion, but rather is the result of a gradually-increasing heart weak- ness from cardiac-muscle degeneration, which may be precipitated by any sudden exertion, but more frequently is the result of the principle of " all or nothing," the transition from " all " to " nothing " being necessarily rapid.7. The cardiac physical signs in beri-teri closely resemble those found in diphtheria and are of paramount importance in prognosis and treatment.
Dexamethasone accelerates catabolism of leukotriene C<sub>4</sub>in bronchial epithelial cells
Authors: M. Zaitsu, Y. Hamasaki, K. Tsuji, M. Matsuo, I. Fujita, Y. Aoki, E. Ishii, O. Kohashi
Journal: European Respiratory Journal (2003)

Leukotriene (LT)C 4 , a potent chemical mediator in bronchial asthma, is metabolised to the less active LTE 4 via LTD 4 in two consecutive reactions catalysed by enzymes of the glutamyl transpeptidase and dipeptidase families. The activities of these catabolic enzymes may be influenced by glucocorticosteroids. This study was conducted to examine whether this inactivation of LTC 4 is affected by dexamethasone (DEX) in transformed human bronchial epithelial cells and normal human bronchial epithelial cells. After incubation with DEX for 0–5 days, cells were resuspended in the presence of exogenous LTC 4 , and conversion of LTC 4 to LTE 4 was measured using high-performance liquid chromatography. γ‐Glutamyl transpeptidase (GGT) and GGT-related enzyme (GGTRE) messenger ribonucleic acid (mRNA) expression were examined using reverse transcriptase-polymerase chain reaction analysis, and GGT activity by enzyme assay. Conversion to LTE 4 was accelerated by DEX pretreatment. GGTRE but not GGT mRNA expression was enhanced after incubation with DEX. The results indicate that dexamethasone transcriptionally upregulates the activity of γ‐glutamyl transpeptidase-related enzyme in human bronchial epithelial cells, which accelerates inactivation of leukotriene C 4 via conversion to leukotriene E 4 . This is a novel mechanism of glucocorticosteroids in human bronchial epithelial cells.
An unusual cause of acute pancreatitis?
Authors: R Noun, S Zeidan, E Riachy, K Honein
Journal: Gut (2006)

A 70-year-old woman presented with a 48-h history of acute epigastric pain, nausea and non-bilious vomiting. Her medical history included hypertension, appendicectomy and recurrent right upper quadrant pain 2–3 times weekly for the past 3 months. No dyslipidaemia or alcoholism were …
Recorded consultations for children under 5 have increased considerably in general practice
Authors: A. R Del Mar
Journal: BMJ (1996)

explicable by Guus A de Jonge and Adele C Engelberts's comments on secondary sleeping position, since the proportion of boys among infants found in the prone position was 53/77 (69%) in the cases and 28/45 (62%) in the con- trols, in the side position 22/43 (51%) and 41/92 (45%) respectively, and in the supine position 36/67 (54%) and 311/618 (50%) respectively.Thus among the babies who died more boys than girls rolled from their side to prone during the final sleep.
Determining the aetiology of pulmonary oedema by the oedema fluid-to-plasma protein ratio
Authors: L. B. Ware, R. D. Fremont, J. A. Bastarache, C. S. Calfee, M. A. Matthay
Journal: European Respiratory Journal (2009)

We hypothesised that the oedema fluid-to-plasma protein (EF/PL) ratio, a noninvasive measure of alveolar capillary membrane permeability, can accurately determine the aetiology of acute pulmonary oedema. 390 mechanically ventilated patients with acute pulmonary oedema were enrolled. A clinical diagnosis of acute lung injury (ALI), cardiogenic pulmonary oedema or a mixed aetiology was based on expert medical record review at the end of hospitalisation. The EF/PL ratio was measured from pulmonary oedema fluid and plasma samples collected at intubation. 209 patients had a clinical diagnosis of ALI, 147 had a diagnosis of cardiogenic pulmonary oedema and 34 had a mixed aetiology. The EF/PL ratio had an area under the receiver-operating curve of 0.84 for differentiating ALI from cardiogenic pulmonary oedema. Using a predefined cut-off of 0.65, the EF/PL ratio had a sensitivity of 81% and a specificity of 81% for the diagnosis of ALI. An EF/PL ratio ≥0.65 was also associated with significantly higher mortality and fewer ventilator-free days. Noninvasive measurement of the EF/PL ratio is a safe and reliable bedside method for rapidly determining the aetiology of acute pulmonary oedema that can be used at the bedside in both developed and developing countries.
Single injection sustained release angiopeptin for prevention of late clinical events following coronary angioplasty
Authors: H. Emanuelsson, M. Aasa, P. Albertsson, O. Amtorp, J.-P. Bagger, M.L. Foegh, J. Heikkilä, J.J. Popma, J. Renstrup, K Saunamäki, P. Thayssen
Journal: Journal of the American College of Cardiology (1998)
Propionibacterium acnes in granulomas of a patient with necrotising sarcoid granulomatosis
Authors: T Arai, Y Inoue, Y Eishi, S Yamamoto, M Sakatani
Journal: Thorax (2007)

relationship between bronchial hyperresponsiveness (BHR) and physical activity.Several hypotheses are invoked to explain this association, including a suggestion that physical activity reduces bronchial inflammation by altering airway physiology.Their major hypothesis is that obesity reduces physical activity and that it is this reduction in physical activity which causes, in some mysterious way, the increase in BHR observed.Their proposed mechanism-that this lack of exercise is associated with a decrease in deep inspiration-is truly breathtaking.We suggest a much more obvious explanation, which is supported by the published evidence.In our recent survey reported in Thorax 2 we demonstrated a highly signifi- cant association of body mass index with chronic cough.Other associations observed in this study infer that the cough of obesity is reflux in nature.If obesity leads to refluxrelated respiratory symptoms, can this form of upper airway reflux cause BHR?Unfortunately, Shaaban et al 1 do not provide us with any information concerning the incidence of classic reflux symptoms in their population.In a study of patients with dyspepsia and endoscopically proven gastrooesophageal reflux by Bagnato et al, 3 over one-third had significant BHR.These subjects had no personal/family history or symptoms suggestive of asthma.However, about two-fifths of patients in the study by Shaaban et al had asthma-like symptoms, defined as wheeze and sedentary breathlessness.We suggest that these patients could still have reflux-related symptoms as one-third of patients with chronic reflux cough, as demonstrated by pH monitoring, complain of exertional wheeze and dyspnoea. 4 With the rising levels of obesity in the population, the accurate recognition of the aetiology of the associated BHR is vital to avoid the spurious diagnosis of ''late onset'' asthma.Perhaps reflux asthma would be a better-but, as yet, unproven-term.
The T wave of the electrocardiogram during and after exercise in normal subjects
Authors: A. H. KITCHIN, J. M. NEILSON
Journal: Cardiovascular Research (1972)

In normal subjects the electrocardiographic T wave decreases in amplitude during exercise. Immediately after exercise the T amplitude increases, and there is a rise in the ST segment and in its slope. These changes, which may be due to alterations of sympathetic tone, are relevant to the interpretation of ECG exercise tests.
Malignant mesothelioma. A survival analysis of 123 consecutive cases at an occupational clinic
Authors: Ellen Marie Lund Skammeritz, Lars Haukali Hvass Omland, Jens Peter Johansen, Øyvind Omland
Journal: European Respiratory Journal (2012)

Aim. To describe the asbestos exposure, to identify factors associated to the prognosis, and to calculate the medial survival time in 123 consecutive patients (1984-2010) with patological verified diagnosis of malignant mesothelioma (MM).  Method. From medical records we identified age, sex, asbestos fibres exposure, localisation and subtypes of MM, performance status, and treatment.  Results. Median age was 65 years (min. 41 - max. 90) and 111 (90.2%) were men and 12 (9.8%) were women. We identified asbestos exposure in 112 (91%) patients. Major contributers were industries of shipbuilding (30%), construction (22%), asbestos-cement (17%), metal (8%), and automobile repair (6%). 2 years survival for MM in pleura % (95% CI) were: 19 (12-30), peritoneum: 24 (8-74), pleura and peritoneum/pericardium: 25 (5-100), and tunica vaginalis: 100 (100-100). In Cox regression survival analysis for all cases but tunica vaginalis (N=120) significant variables for mortality rate ratio (MRR) (95% CI) were male sex: 2.26 (1.10-5.08) and performance status > 2: 5.01 (2.66-9.43). In a model restricted to MM in pleura (N=78) significant variables were male sex: 6.95 (1.29-37.38), sakromatiod subtype: 6.10 (1.93-19.33), performance status > 1: 4.64 (2.08-10.37), and time after trimodal treatment 0.25 (0.07-0.96).  Conclusion: Asbestos exposure was identified in 91% of the patients, shipbuilding-,constructing-, and asbestos-cement industry accounted for > 2/3 of the cases. 2 years survival for MM was 19% to 25% in pleura and peritoneum, in tunica vaginalis 100%. Male sex, low performance status, and sarkomatiod subtype lower while trimodal treatment enhance survival time.
Thyroid hormone action. Demonstration of similar receptors in isolated nuclei of rat liver and cultured GH1 cells.
Authors: H H Samuels, J S Tsai
Journal: Journal of Clinical Investigation (1974)

High-affinity, limited-capacity nuclear binding activities, putative receptors for triiodothyronine, were detected after incubation of hormone with intact rat pituitary GH1 cells in culture, isolated GH1 cell nuclei, or rat liver nuclei. The total number of triiodothyronine binding sites per nucleus was similar in each case (approximately 8,000). The estimated equilibrium dissociation constants were virtually identical in isolated GH1 cell nuclei and rat liver nuclei, and both values were similar to that determined in intact GH2 cells. These results suggest that mechanisms of thyroid hormone action defined in cell culture could apply to thyroid hormone regulatory effects in vivo.