tbuckley/cabot-search huggingface dataset:
Multicenter Phase II Study of Mogamulizumab (KW-0761), a Defucosylated Anti-CC Chemokine Receptor 4 Antibody, in Patients With Relapsed Peripheral T-Cell Lymphoma and Cutaneous T-Cell Lymphoma
Authors: Michinori Ogura, Takashi Ishida, Kiyohiko Hatake, Masafumi Taniwaki, Kiyoshi Ando, Kensei Tobinai, Katsuya Fujimoto, Kazuhito Yamamoto, Toshihiro Miyamoto, Naokuni Uike, Mitsune Tanimoto, Kunihiro Tsukasaki, Kenichi Ishizawa, Junji Suzumiya, Hiroshi Inagaki, Kazuo Tamura, Shiro Akinaga, Masao Tomonaga, Ryuzo Ueda
Journal: Journal of Clinical Oncology (2014)

CC chemokine receptor 4 (CCR4) is expressed by peripheral T-cell lymphomas (PTCLs) and is associated with poor outcomes. Mogamulizumab (KW-0761) is a defucosylated humanized anti-CCR4 antibody engineered to exert potent antibody-dependent cellular cytotoxicity. This multicenter phase II study evaluated the efficacy and safety of mogamulizumab in patients with relapsed PTCL and cutaneous T-cell lymphoma (CTCL).Mogamulizumab (1.0 mg/kg) was administered intravenously once per week for 8 weeks to patients with relapsed CCR4-positive PTCL or CTCL. The primary end point was the overall response rate, and the secondary end points included safety, progression-free survival (PFS), and overall survival (OS).A total of 38 patients were enrolled, and 37 patients received mogamulizumab. Objective responses were noted for 13 of 37 patients (35%; 95% CI, 20% to 53%), including five patients (14%) with complete response. The median PFS was 3.0 months (95% CI, 1.6 to 4.9 months), and the median OS was not calculated. The mean maximum and trough mogamulizumab concentrations (± standard deviation) after the eighth infusion were 45.9 ± 9.3 and 29.0 ± 13.3 μg/mL, respectively. The most common adverse events were hematologic events, pyrexia, and skin disorders, all of which were reversible and manageable.Mogamulizumab exhibited clinically meaningful antitumor activity in patients with relapsed PTCL and CTCL, with an acceptable toxicity profile. Further investigation of mogamulizumab for treatment of T-cell lymphoma is warranted.
Assessment of the Role of Inheritance in Sleep Apnea Syndrome
Authors: Giora Pillar, Peretz Lavie
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Several reports have suggested a genetic importance in the pathogenesis of the sleep apnea syndrome (SAS). In this study, all adult (> 16 yr of age) offspring of 45 randomly selected parents with previously diagnosed SAS were asked to undergo a whole-night polysomnographic study. One hundred and five of 120 candidates participated in the study (66M:39F), with a high rate of compliance. Forty-seven percent of the offspring (36 males and 13 females; mean age, 32 yr) were found to have SAS. These results appear considerably higher (p < 0.001) than the common estimation of the prevalence of SAS in the population (4%). Another 21.9% of the offspring were "simple snorers" (17 males and 6 females; mean age, = 26 yr). Thirty-one percent were unaffected (13 males, 20 females; mean age, 29 yr). Only 16% of males over 35 yr of age were unaffected. In the single family studied in which both parents were affected, all three of their children (sons) had SAS: two grandsons older than 16 yr were simple snorers. Considering the well-established prevalence of SAS in the general population (1 to 4%), these results may suggest that SAS is an inherited syndrome.
The value of perinatal immune responses in predicting allergic disease at 6 years of age
Authors: S. L. Prescott, B. King, T. L. Strong, P. G. Holt
Journal: Allergy (2003)

Background: Characterizing early abnormalities in immune development of allergic individuals provides an important basis for defining disease pathogenesis and future prevention strategies. This study compares patterns of early immune responses in an established cohort based on allergic outcomes and allergen skin prick test (SPT) reactions at 6 years of age. Methods: Children from an original birth cohort ( n = 60) consisting of 44 high risk (HR) (family history of allergy) and 16 low risk (LR) (no family history) were reassessed at 6 years of age. Detailed clinical information about allergic disease was obtained ( n = 53) and a subgroup ( n = 31) consented to have allergen SPT to common food and inhalant allergens. Data from previous immunological assessments performed at birth, 1 and 2 years of age, including lymphoproliferation and cytokine [interleukin (IL)‐4, IL‐5, IL‐6, IL‐10, IL‐13 and interferon (IFN)‐ γ ] responses to ovalbumin (OVA), house dust mite (HDM), cat allergen (Fel d 1), phytohaemaglutinin (PHA) and tetanus toxoid, were re‐analysed based on the 6‐year clinical outcomes. Results: Twenty‐eight HR and three LR children had a clinical history of allergic disease at 6 years of age including doctor diagnosed asthma ( n = 17) and/or eczema ( n = 24). Most children (78%) with atopy at 6 years had positive SPT to the allergens tested, and 70% had symptoms within the last year. Children at genetic risk (family history) of allergy had weaker ( P = 0.017) polyclonal T helper 1 (Th1) IFN‐ γ responses in the neonatal period compared with LR children. Although children with allergic disease at 6 years also tended to have weaker neonatal IFN‐ γ responses compared to those with no symptoms, but this was not quite significant ( P = 0.05). A positive SPT to HDM at 6 years was associated with higher IL‐13 responses to HDM at 1 year ( P = 0.02), whereas allergic disease at 6 years was associated with higher IL‐5 messenger RNA (mRNA) responses to HDM at 1 year ( P = 0.01). Despite these associations, regression analysis demonstrated that the only significant early predictors of allergic sensitization at 6 years of age were a family history of allergic disease, and atopic symptoms at 2 years. Importantly, none of the early immunological parameters measured were significantly predictive of allergic disease or allergic sensitization in these 6‐year‐olds. Conclusions: Although our observations suggest that subtle differential alterations in cytokine responses during early immune development are associated with different aspects of subsequent atopy, there are still no early predictive biomarkers of disease. A positive family history of allergy remains the dominant predictive factor.
Michael John Davies
Authors: C. Corbishley
Journal: BMJ (2003)

British Heart Foundation professor of cardiovascular pathology St George's Hospital Medical School, London, 1981-2001 (b Eltham, London, 1937; q Middlesex Hospital Medical School, London, 1961; MD, FRCPath), died from metastatic colorectal cancer on 18 February 2003.

In 1969 Michael Davies was appointed senior lecturer in pathology at St George's, where he was to spend the rest of his career. He progressed to become reader in cardiac pathology in 1973, professor of cardiac pathology in 1977 (a personal chair), and, in 1981, the first British Heart Foundation professor of cardiovascular pathology. His contribution to our understanding of acquired heart disease, notably the dynamics of coronary atherosclerosis, was remarkable. Of no less significance was his original work on conduction system abnormalities, valve disease, and the cardiomyopathies. He was editor in chief of Heart (formerly the British Heart Journal) from 1991 to 1999. He leaves a wife, Anthea, and two children.
Institutionalization of Patients With Hip Fractures
Authors: Ronald Koshes
Journal: JAMA (1983)

<h3>To the Editor.—</h3> "Hip Fractures in the Elderly" (1982;248:564) brings to light an important issue related to the medical reason for nursing home placement. It is largely an unexplored area, despite the fact that it is the physician who ultimately makes the application for institutionalization. The high percentage of patients with hip fractures who were institutionalized in this study, 41%, is surprising and alarming. At any particular time, there is only a small population of patients with hip fractures residing in nursing homes: 8.3% of the total nursing home population in 1977 had hip fractures.<sup>1</sup>The above data suggest that the decision of institutionalization made after discharge from this particular hospital was not made appropriately. It is possible that the functional scale used in the study would be more appropriately used in the decision-making process for institutionalization<i>v</i>discharge to the community. The patients who were predicted to be
Commentary: Assessing the effects of environmental pollution when people know that they have been exposed
Authors: R T Mayon-White
Journal: BMJ (1997)

Objective: To evaluate the immunogenicity and reactogenicity of a new triple S recombinant hepatitis B vaccine in a cohort of healthy people in whom currently licensed hepatitis B vaccines had persistently not induced an immune response.Design: Single centre, randomised, double blind, dose-response study.Setting: Research vaccine evaluation centre at a teaching hospital.Subjects: 100 healthcare workers aged 18-70 years with a history of failure to seroconvert after at least four doses of a licensed hepatitis B vaccine containing the S component.Intervention: Each subject was randomly allocated two doses of 5, 10, 20, or 40 g of a new hepatitis B vaccine two months apart.Main outcome measures: Immunogenicity of the four doses.Seroconversion and seroprotection were defined as an antibody titre > 10 IU/l and > 100 IU/l respectively against an international antibody standard.Results: 69 subjects seroconverted after a single dose of the vaccine.After the booster vaccination one other subject seroconverted, bringing the overall seroconversion rate to 70%.Fifteen subjects given 5 g of vaccine, 19 given 10 g, 16 given 20 g, and 20 given 40 g seroconverted.Seroconversion rates in the four antigen dose groups were 60% (15/25), 76% (19/25), 64% (16/25), and 80% (20/25).After the booster dose there was no significant dose-response effect on the overall seroconversion rate, although the small sample size meant that a clinically important dose-response could not be ruled out. Conclusion:A single dose of 20 g of the vaccine was as effective as two doses of either 40 g or 20 g of this vaccine formulation in terms of seroconversion, seroprotection, and geometric mean titres.
Immediate Therapy for the Acute Attack of Asthma
Authors: Herman H. Pinkerton, Thomas E. Van Metre
Journal: New England Journal of Medicine (1958)

SINCE one of the major problems in the therapy of bronchial asthma is to provide rapid relief to the patient suffering with severe wheezing, accurate data on the relative rapidity of relief provided by the different therapeutic agents available are required.The corticosteroids have been in use in certain selected forms of bronchial asthma for eight years.1 2 3 During the last two years, there has been considerable experience with prednisone and prednisolone, which have been found to be effective in providing relief for the asthmatic patient4 5 6 and lack the salt-retaining qualities that characterize many therapeutically effective related compounds.7 , 8 Their ultimate effectiveness . . .
Expression of a fusogenic membrane glycoprotein by an oncolytic herpes simplex virus potentiates the viral antitumor effect
Authors: Xinping Fu, Lihua Tao, Aiwu Jin, Richard Vile, Malcolm K Brenner, Xiaoliu Zhang
Journal: Molecular Therapy (2003)

Oncolytic viruses have shown considerable promise in the treatment of solid tumors, but their potency must be improved if their full clinical potential is to be realized. We inserted the gene encoding a truncated form of the gibbon ape leukemia virus envelope fusogenic membrane glycoprotein (GALV.fus) into an oncolytic herpes simplex virus, using an enforced ligation procedure. Subsequent in vitro and in vivo studies showed that expression of GALV.fus in the context of an oncolytic virus significantly enhances the antitumor effect of the virus. Furthermore, by controlling GALV.fus expression through a strict late viral promoter, whose activity depends on the initiation of viral DNA replication, we were able to express this glycoprotein in tumor cells but not in normal nondividing cells. It will be of interest to confirm whether functional expression of a strong fusogenic gene by an oncolytic herpes simplex virus enhances viral antitumor activity without increasing its toxicity.
Tropomodulin 1 Expression Driven by NF-κB Enhances Breast Cancer Growth
Authors: Taku Ito-Kureha, Naohiko Koshikawa, Mizuki Yamamoto, Kentaro Semba, Noritaka Yamaguchi, Tadashi Yamamoto, Motoharu Seiki, Jun-ichiro Inoue
Journal: Cancer Research (2014)

Abstract Triple-negative breast cancers (TNBC), which include the basal-like and claudin-low disease subtypes, are aggressive malignancies for which effective therapeutic targets are lacking. NF-κB activation has an established role in breast malignancy, and it is higher in TNBC than other breast cancer subtypes. On this basis, we hypothesized that proteins derived from NF-κB target genes might be molecular targets for TNBC therapy. In this study, we conducted a microarray-based screen for novel NF-κB–inducible proteins as candidate therapeutic targets, identifying tropomodulin 1 (TMOD1) as a lead candidate. TMOD1 expression was regulated directly by NF-κB and was significantly higher in TNBC than other breast cancer subtypes. TMOD1 elevation is associated with enhanced tumor growth in a mouse tumor xenograft model and in a 3D type I collagen culture. TMOD1-dependent tumor growth was correlated with MMP13 induction, which was mediated by TMOD1-dependent accumulation of β-catenin. Overall, our study highlighted a novel TMOD1-mediated link between NF-κB activation and MMP13 induction, which accounts in part for the NF-κB–dependent malignant phenotype of TNBC. Cancer Res; 75(1); 62–72. ©2014 AACR.
Increased Risk of Acute Pancreatitis and Biliary Disease Observed in Patients With Type 2 Diabetes
Authors: Rebecca A. Noel, Daniel K. Braun, Ruth E. Patterson, Gary L. Bloomgren
Journal: Diabetes Care (2009)

The objective of this study was to assess the risk of acute pancreatitis in patients with type 2 diabetes compared with that in patients without diabetes. We also examined the risk of biliary disease (defined as occurrence of cholelithiasis, acute cholecystitis, or cholecystectomy), which is a major cause of pancreatitis.We conducted a retrospective cohort study using a large, geographically diverse U.S. health care claims database. Eligible patients (>or=18 years) were enrolled for at least 12 continuous months (1999-2005), with no incident events of pancreatitis or biliary disease during that 1 year baseline period. ICD-9 codes and prescription data were used to identify patients with type 2 diabetes; ICD-9 codes were also used to identify cases of pancreatitis and biliary disease. Overall, 337,067 patients with type 2 diabetes were matched on age and sex with 337,067 patients without diabetes. Incidence rates of disease and 95% CI were calculated per 100,000 person-years of exposure.The type 2 diabetic cohort had a 2.83-fold (95% CI 2.61-3.06) greater risk of pancreatitis and 1.91-fold (1.84-1.99) greater risk of biliary disease compared with the nondiabetic cohort. Relative to patients of corresponding age without diabetes, younger type 2 diabetic patients had the highest risk of pancreatitis (<45 years: incidence rate ratio [IRR] 5.26 [95% CI 4.31-6.42]; >or=45 years: 2.44 [2.23-2.66]).These data suggest that patients with type 2 diabetes may have an increased risk of acute pancreatitis and biliary disease.
5 The impact of outpatient partial booking on dermatology clinic activity
Authors: C.R. Charman, J.S. English
Journal: British Journal of Dermatology (2003)

The Outpatient Partial Booking system has been introduced across the UK as part of the Government's national targets to improve NHS outpatient performance. The system requires patients to contact the hospital to make their appointment, potentially allowing patients to chose a convenient appointment date and therefore reduce non‐attendances. On receipt of the GP referral letter patients are sent an ‘acknowledgement’ letter, with a further ‘contact’ letter sent four weeks before appointment availability requesting that the patient telephone to book an appointment. Patients failing to phone after 2 weeks are sent a ‘reminder’ letter and subsequently discharged after 2 further weeks if they fail to respond. The system has been applied to new ‘routine’ outpatient appointments, and has been operational in our Dermatology Department since March 2002. The aim of this study was to compare the proportion of new patients failing to attend their Dermatology outpatient appointment before and after the introduction of Partial Booking. Data for all new general dermatology outpatient referrals was collected for two 4‐month periods, before and after the introduction of the system. Between September 2001 and December 2001 inclusive, of the 1994 new referrals, 235 patients failed to attend (11.8%). Between September 2002 and December 2002 inclusive there were 2735 new clinic referrals, 202 of whom failed to attend (7.4%) (chi‐square test P < 0.001). Over a 6‐month period of Partial Booking, 27.8% of patients sent a ‘contact letter’ required a ‘reminder’ letter, with 10.3% being subsequently discharged before the clinic date. A further 2.9% of patients phoned to decline their appointment prior to clinic. Analysis of GP referral letters for 100 consecutive patients who failed to respond to the ‘reminder letter’ showed that 70% of non‐responders were ≤ 35 years and 52% were male, with psoriasis (14%) and eczema (14%) being the most common reasons for initial referral.
Inquiry says surgeons should stop operating if patient dies
Authors: B. Christie
Journal: BMJ (1999)

The Scottish royal medical colleges have been urged to consider issuing advice to surgeons to stop operating for the day when a patient dies on the operating table. It follows an inquiry into the deaths of two patients at Falkirk Royal Infirmary-both were operated on by the same surgeon on the same day.

The surgeon, Nigel Harris, was …
Control of sympathetic vasomotor tone by catecholaminergic C1 neurones of the rostral ventrolateral medulla oblongata
Authors: N. Marina, A. P. L. Abdala, A. Korsak, A. E. Simms, A. M. Allen, J. F. R. Paton, A. V. Gourine
Journal: Cardiovascular Research (2011)

Increased sympathetic tone in obstructive sleep apnoea results from recurrent episodes of systemic hypoxia and hypercapnia and might be an important contributor to the development of cardiovascular disease. In this study, we re-evaluated the role of a specific population of sympathoexcitatory catecholaminergic C1 neurones of the rostral ventrolateral medulla oblongata in the control of sympathetic vasomotor tone, arterial blood pressure, and hypercapnia-evoked sympathetic and cardiovascular responses. In anaesthetized rats in vivo and perfused rat working heart brainstem preparations in situ, C1 neurones were acutely silenced by application of the insect peptide allatostatin following cell-specific targeting with a lentiviral vector to express the inhibitory Drosophila allatostatin receptor. In anaesthetized rats with denervated peripheral chemoreceptors, acute inhibition of 50% of the C1 neuronal population resulted in ∼50% reduction in renal sympathetic nerve activity and a profound fall in arterial blood pressure (by ∼25 mmHg). However, under these conditions systemic hypercapnia still evoked vigorous sympathetic activation and the slopes of the CO2-evoked sympathoexcitatory and cardiovascular responses were not affected by inhibition of C1 neurones. Inhibition of C1 neurones in situ resulted in a reversible fall in perfusion pressure and the amplitude of respiratory-related bursts of thoracic sympathetic nerve activity. These data confirm a fundamental physiological role of medullary catecholaminergic C1 neurones in maintaining resting sympathetic vasomotor tone and arterial blood pressure. However, C1 neurones do not appear to mediate sympathoexcitation evoked by central actions of CO2.
Letter: Bottle-feeding.
Authors: J S Bradshaw
Journal: BMJ (1976)

of the baby are impossible to carry out.Nevertheless, all the indications are that the practice is nearly always, in hot countries or cold, unnecessary and undesirable.Newborn babies often need frequent body contact and always require abundant opportunities to suckle.Their mothers, no less, need support and encouragement, as is recommended by the authors of the study.
Two joints are more than twice one joint
Authors: Jeroen B. J. Smeets
Journal: Behavioral and Brain Sciences (1995)

Abstract An alternative multi-joint extension to the lambda model is proposed. According to this extension, the activity of a muscle depends not only on the difference between lambda and length of that muscle, but also on the difference between lambda and length of other muscles. This 2-D extension can describe more neurophysiological experiments than the extension proposed in the target article.
Suppression of Human Prostate Tumor Growth in Mice by a Cytolytic <scp>d</scp>-, <scp>l</scp>-Amino Acid Peptide
Authors: Niv Papo, Amir Braunstein, Zelig Eshhar, Yechiel Shai
Journal: Cancer Research (2004)

Abstract Gene-encoded host defense peptides are used as part of the innate immunity, and many of them act by directly lysing the cell membrane of the pathogen. A few of these peptides showed anticancer activity in vitro but could not be used in vivo because of their inactivation by serum. We designed a 15-amino acid peptide, composed of d- and l-amino acids (diastereomer), which targets both androgen-independent and androgen-dependent human prostate carcinoma cell lines (CL1, 22RV1, and LNCaP). Most importantly, we observed a complete arrest of growth in CL1 and 22RV1 xenografts treated intratumorally with the diastereomer. This was also accompanied by a lowering of prostate-specific antigen serum levels secreted by the 22RV1 xenograft. Furthermore, the diastereomer synergized with conventional chemotherapeutics. In contrast, the parental all l-amino acids peptide was highly active only in vitro and could not discriminate between tumor and nontumor cells. Fluorescent confocal microscopy, histopathologic examination, and cell permeability studies (depolarization of transmembrane potential and release of an encapsulated dye) suggest a necrotic mechanism of killing, after a threshold concentration of peptide has been reached. Its destructive killing effect and the simple sequence of the diastereomer make it an attractive chemotherapeutic candidate possessing a new mode of action, with potential to be developed additionally for the treatment of prostate carcinoma.