tbuckley/cabot-search huggingface dataset:
Syk mediates airway hyper-responsiveness and airway remodeling in a chronic mouse model of house dust mite induced allergic airways disease
Authors: Chung-Wai Chow, Sepehr Salehi, Xiaomin Wang, Krystal Godri Pollit, Jamila Chakir, Jeremy Scott
Journal: European Respiratory Journal (2013)

BACKGROUND:  Asthma is characterized by airways hyper-responsiveness (AHR), chronic inflammation, remodeling and reversible obstruction. We have shown treatment with Syk (spleen tyrosine kinase) inhibitor to abrogate AHR to methacholine (MCh) in a mouse model of established ovalbumin-induced airways inflammation. The role of Syk in airway remodeling is not known.   OBJECTIVE:  To investigate the role of Syk in the pathogenesis of AHR and remodeling in a mouse model of allergic airways inflammation.   METHODS:  We used acute and chronic mouse models of house dust mite-induced (HDM;  Dermatophagoides farina  and  D. pteronyssinus,  respectively) airways inflammation. The role of Syk was investigated by pharmacological inhibition and in Syk flox/flox //rosa26CreER T2  conditional knockout mice. Respiratory mechanics and MCh-responsiveness were assessed using the flexiVent® system, and airway remodeling determined by semi-quantitative histological analysis.   RESULTS:  AHR in response to HDM was abrogated in the Syk knockout when compared with Syk-expressing mice. Similarly, AHR was reduced to control levels in response to a single dose of the Syk inhibitor, NVP-QAB-205, given intratracheally after establishment of allergic airways inflammation. Airways inflammation was not affected by either Syk knockout or NVP-QAB-205. Histological analysis indicated fibrosis, epithelial thickening, mucus cell hyperplasia and smooth muscle cell hypertrophy to be attenuated in the Syk knockout model when compared with Syk-expressing controls.   CONCLUSIONS:  These studies suggest that Syk mediates AHR and airway remodeling in a chronic model of allergen-induced airways inflammation.
THE INTERNAL ENVIRONMENT AND BEHAVIOR
Authors: ROSS A. MCFARLAND
Journal: American Journal of Psychiatry (1941)

In this paper the importance of constancy in the internal environment for the stability and well being of the organism as a whole and the cerebral cortex in particular has been emphasized. Numerous illustrations were cited from studies at high altitude to demonstrate the basic rôle of oxygen in neural activity. The way in which psychological functions can be altered by changes in the oxygen tension was illustrated by reference to specific experiments in neuro-muscular control, memory and light sensitivity. The results showed in striking fashion how sensitive psycho-physiological processes are to oxygen changes in the internal environment. The application of these observations and experimental findings were then discussed in relation to certain mental disorders. By placing these familiar psychological and psychiatric problems in this new setting they are seen in broader perspective for further study.
Two-Photon Excitation Fluorescence Microscopy
Authors: Peter T. C. So, Chen Y. Dong, Barry R. Masters, Keith M. Berland
Journal: Annual Review of Biomedical Engineering (2000)

▪ Abstract Two-photon fluorescence microscopy is one of the most important recent inventions in biological imaging. This technology enables noninvasive study of biological specimens in three dimensions with submicrometer resolution. Two-photon excitation of fluorophores results from the simultaneous absorption of two photons. This excitation process has a number of unique advantages, such as reduced specimen photodamage and enhanced penetration depth. It also produces higher-contrast images and is a novel method to trigger localized photochemical reactions. Two-photon microscopy continues to find an increasing number of applications in biology and medicine.
Tumors of the Esophagus and Duodenum Induced in Mice by Oral Adm.inistration of N-Ethyl-N′-Nitro-N-Nitrosoguanidine2
Authors: Takaaki Nakamura, Mutsushi Matsuyama, Hidemasa Kishimoto
Journal: JNCI Journal of the National Cancer Institute (1974)

N-Ethyl-N′-nitro-N-nitrosoguanidine (ENNG) fed in drinking water to CBA/H-T6 mice produced squamous cell carcinomas of the esophagus and adenocarcinomas of the duodenum in about one-third of the animals over a period of 355–540 days. Many of the tumors invaded the adjacent organs.
Aminomethyl spectinomycins as therapeutics for drug-resistant respiratory tract and sexually transmitted bacterial infections
Authors: David F. Bruhn, Samanthi L. Waidyarachchi, Dora B. Madhura, Dimitri Shcherbakov, Zhong Zheng, Jiuyu Liu, Yasser M. Abdelrahman, Aman P. Singh, Stefan Duscha, Chetan Rathi, Robin B. Lee, Robert J. Belland, Bernd Meibohm, Jason W. Rosch, Erik C. Böttger, Richard E. Lee
Journal: Science Translational Medicine (2015)

A new series of spectinomycin analogs with potency against drug-resistant bacterial pathogens was designed and developed with a structure-based approach and validated in vitro and in vivo.
Sequential hydroxyurea-cytarabine chemotherapy for refractory non-Hodgkin's lymphoma.
Authors: R L Schilsky, S F Williams, J E Ultmann, S Watson
Journal: Journal of Clinical Oncology (1987)

In experimental systems, hydroxyurea (HU) and cytarabine (ara-C) produce synergistic cytotoxicity to murine and human leukemia cells due to both cytokinetic and biochemical interactions that tend to enhance the effectiveness of ara-C. Therefore, we began a phase II trial of the combination of HU and ara-C to determine the efficacy and toxicity of this combination in treatment of patients with refractory non-Hodgkin's lymphoma. Chemotherapy began with HU 500 mg administered orally every six hours for four doses. Twelve hours following the fourth HU dose, ara-C 100 mg/m2/d was administered by continuous intravenous (IV) infusion for three days. Concomitantly with the three-day ara-C infusion, patients again received HU 500 mg orally every four hours. Cycles of therapy were repeated every 28 days. Twenty-five patients ranging in age from 26 to 70 years were enrolled in the study. Of 21 patients evaluable for response, nine (43%) obtained complete (CR) or partial remissions (PR). Most responding patients had either large-cell or cutaneous T cell lymphoma, and all but two had a performance status of 0 to 1 at entry in the study. The median survival for all responding patients was 13 months compared with 2.5 months for nonresponders. Patients obtaining a CR had a median survival of 27.5 months, and two of the four CRs remain alive and in remission at 10+ and 30+ months from achievement of CR status. The primary toxic effect of this regimen was bone marrow suppression. The median WBC nadir was 2,200 cells/microL, and the median platelet nadir was 80,000/microL. Other toxicities included mild nausea and vomiting and diffuse maculopapular rash. This biochemically rational approach to enhancing ara-C activity may have significant clinical utility and should be further explored in treatment of patients with large-cell and cutaneous T cell lymphomas.
A worse cardiac function revealed by TDI in patients with congestive heart failure and Cheyne-Stokes breathing
Authors: Donato Lacedonia, Michele Correale, Giovanna E. Carpagnano, Tommaso Passero, Lucia Forte, Matteo di Biase, Maria P. Foschino Barbaro
Journal: European Respiratory Journal (2013)

Background

Tissue Doppler Imaging (TDI) is used to better stratify dead risk in patients with congestive heart failure. Up today few studies have used this method to investigate the differences between patients with HF and Cheyne-Stokes breathing (CSB) with ones who haven’t it. The aim of this study was to evaluate the impact of CSB on myocardic function by TDI.

Materials and Methods

50 consecutive patients who afferent to Heart Failure Unit of University of Foggia were studied by conventional and Tissue Doppler echocardiography, and underwent to nocturnal poligraphy to evaluate the presence of sleep apnea and CSB.

Results

Mean age was 61,9±11,3 years, LVEF 38,41±11,5% and BMI was 31,6±3,9. 10 patients (20%) had high prevalence of CSB during the night. There wasn’t any differences between this group and others ones about age, BMI, LVEF but there were many differences at TDI. Respect to patients without CSB, in ones who had it, late (A’) diastolic peak velocity was lower (5,47±2,3 vs 7,9±2,6, p=0.04); the ratio of early to late diastolic velocity (E’/A’) was higher (1,70±1,48 vs 0,76±0,31, p<0.01); EAS index [E'/(A' x S')] was higher (0,36±0,29 vs 0,16±0,11, p<0.01) and Isovolumic Relaxation Time (IRT) was lower (60,35±36,6 vs 113,5±48,3, p=0,04). There was also a positive correlation between percentage of CSB during the night and EAS index (0,76, p<0.01) and E’/A’ (0,88, p<0.001). The presence of obstructive sleep apnea did not influenced this results.

Conclusions

Patients with HF and CSB have a worse cardiac function in compare with ones who haven’t it. This condition is better evaluate by TDI that conventional echocardiography.
DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma.
Authors: H S Friedman, R E McLendon, T Kerby, M Dugan, S H Bigner, A J Henry, D M Ashley, J Krischer, S Lovell, K Rasheed, F Marchev, A J Seman, I Cokgor, J Rich, E Stewart, O M Colvin, J M Provenzale, D D Bigner, M M Haglund, A H Friedman, P L Modrich
Journal: Journal of Clinical Oncology (1998)

PURPOSE We evaluated the response to Temodal (Schering-Plough Research Institute, Kenilworth, NJ) of patients with newly diagnosed malignant glioma, as well as the predictive value of quantifying tumor DNA mismatch repair activity and O6-alkylguanine-DNA alkyltransferase (AGT). PATIENTS AND METHODS Thirty-three patients with newly diagnosed glioblastoma multiforme (GBM) and five patients with newly diagnosed anaplastic astrocytoma (AA) were treated with Temodal at a starting dose of 200 mg/m2 daily for 5 consecutive days with repeat dosing every 28 days after the first daily dose. Immunochemistry for the detection of the human DNA mismatch repair proteins MSH2 and MLH1 and the DNA repair protein AGT was performed with monoclonal antibodies and characterized with respect to percent positive staining. RESULTS Of the 33 patients with GBM, complete responses (CRs) occurred in three patients, partial responses (PRs) occurred in 14 patients, stable disease (SD) was seen in four patients, and 12 patients developed progressive disease (PD). Toxicity included infrequent grades 3 and 4 myelosuppression, constipation, nausea, and headache. Thirty tumors showed greater than 60% cells that stained for MSH2 and MLH1, with three CRs, 12 PRs, three SDs, and 12 PDs. Eight tumors showed 60% or less cells that stained with antibodies to MSH2 and/or MLH1, with 3 PRs, 3 SDs, and 2 PDs. Eleven tumors showed 20% or greater cells that stained with an antibody to AGT, with 1 PR, 2 SDs, and 8 PDs. Twenty-five tumors showed less than 20% cells that stained for AGT, with 3 CRs, 12 PRs, 4 SDs, and 6 PDs. CONCLUSION These results suggest that Temodal has activity against newly diagnosed GBM and AA and warrants continued evaluation of this agent. Furthermore, pretherapy analysis of tumor DNA mismatch repair and, particularly, AGT protein expression may identify patients in whom tumors are resistant to Temodal.
Diagnostic modalities and treatment outcome of tuberculous cervical lymphadenitis (TCL) - Retrospective study in a resource poor setting
Authors: Chandimani Undugodage, Wathsala Gunasinghe, Suharshi De Silva, Kirthi Gunasekera, Amitha Fernando
Journal: European Respiratory Journal (2013)

Background   Sri Lanka has a moderate prevalence for TB and TCL is the commonest form of extra pulmonary tuberculosis. There is a paucity of local data in management of TCL.   Objectives   To describe the diagnostic modalities and treatment outcomes of patients with TCL who presented to the main state referral center in Colombo, Sri Lanka.   Methods   Incident cases of non HIV TCL, during a period of 3 months were analyzed using past records. The diagnosis of TCL was made based on the FNAC (Fine needle aspiration cytology) or EB (excision biopsy). FNAC, EB, Mantoux, culture and treatment outcome at the end of 6 months were assessed. WHO category 1 treatment was given.   Results   We collected 70 records. Majority (46%) was between 20 – 40 year age group with 51 females (73%).  In the sample, 41 (58.5%) had FNAC, 37 (53.1%) had EB. 29 (41%) patients had an EB without a prior FNAC.  TCL was diagnosed in 85% of those with FNAC. 100% of EB were TCL.  Nearly 50% had Mantoux. This was of more than 15mm in 88% (n=31).  7 patients had TB culture reports and all were  Mycobacterium tuberculosis . All had completed 6 months treatment. At the end of 6 months 94% had complete resolution, 6% had persistent nodes. Treatment was extended for more than 6 months in 3%, while 1 patient needed steroids. None had sinus formation.   Conclusions   Several diagnostic methods have been used to diagnose TCL in this sample leading to resource wastage and patient morbidity; this could be averted by setting guidelines on managing TCL in TB prevalent countries.  This data suggests that FNAC can be used as a preliminary investigation in the diagnosis of TCL. A Mantoux test can further support the diagnosis.
Bronchoalveolar lavage fibronectin in patients with sarcoidosis: correlation to hyaluronan and disease activity
Authors: L Bjermer, A Eklund, E Blaschke
Journal: European Respiratory Journal (1991)

Bronchoalveolar lavage was performed in 51 patients with sarcoidosis and in 21 healthy nonsmokers. The concentration of fibronectin was significantly higher (p less than 0.001) in lavage fluid from sarcoid patients (median 267 micrograms.l-1) than in that of controls (46 micrograms.l-1). Furthermore, a significantly higher concentration of fibronectin was found in patients with active disease than in those in whom the disease was inactive (p less than 0.001). In a six month follow-up perspective, patients with a progressive disease course had significantly higher levels of fibronectin than those who had a stable or regressive disorder (p less than 0.01). Correspondingly, lavage hyaluronan was higher (p less than 0.001) in sarcoid patients (55 micrograms.l-1) than in controls (9 micrograms.l-1) and higher (p less than 0.01) in those with active than in those with inactive disease. Patients with progressive disease had higher (p less than 0.01) concentrations of hyaluronan than those in whom the disease was stable. A significant correlation was found between lavage fibronectin levels and hyaluronan (r = 0.81, p less than 0.001). The percentage of mast cells was also higher in patients with active than in those with inactive disease (p less than 0.01) and higher in progressive than in stable sarcoidosis (p less than 0.001). Ten out of 10 patients with progressive disease had mast cells greater than or equal to 0.5%, hyaluronan greater than or equal to 50 micrograms.l-1 and fibronectin greater than or equal to 350 micrograms.l-1 compared to eight out of 41 patients with stable or regressive disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Observations on the Cytology of an Oligodendroglioma Cultivated &lt;italic&gt;In Vitro&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C. M. Pomerat, B. L. Crue, F. H. Kasten
Journal: JNCI Journal of the National Cancer Institute (1964)

Fragments and trypsinized cells from an oligodendroglioma in tissue cultures were examined with cytochemical techniques and phase-contrast, time-lapse cinematography. A new method employing a cadmium sulfide scanner and a strip chart recorder was used to analyze the rhythmic contractile activity of oligodendroglial elements. This graph was compared with those made from cine records available from two previous studies of this rare tumor.
Superoxide Dismutase Activity in 1,2-Dimethylhydrazine-Induced Rat Colon Adenocarcinoma&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: D P Loven, L W Oberley, F M Rousseau, R H Stevens
Journal: JNCI Journal of the National Cancer Institute (1980)

1,2-Dimethylhydrazine-induced large bowel tumors in adult male noninbred Holtzman rats contained greatly elevated levels of copper-zinc-containing superoxide dismutase (Cu-Zn SD) activity when compared to levels in normal intestinal tissue but nearly equal levels of manganese-containing superoxide dismutase (Mn SD) activity. Inasmuch as normal intestinal tissue contains many cell types, SD activities were also measured and compared in isolated intestinal epithelial cells. When compared to the activities in villus cells, Cu-Zn SD activity was greatly increased, whereas Mn SD activity was greatly reduced in tumor cells. The SD activity of tumor cells most nearly resembled that of isolated intestinal crypt cells.
High complete response rate in children with advanced germ cell tumors using cisplatin-containing combination chemotherapy.
Authors: C R Pinkerton, J Pritchard, L Spitz
Journal: Journal of Clinical Oncology (1986)

A consecutive series of 13 children (five girls) with advanced malignant germ cell tumors (MGCTs) were treated with between four and seven (median, six) courses of cisplatin, bleomycin, and either vinblastine (BVP) or VP-16 (BEP). There were seven gonadal primaries (four testis, three ovary) and six at extragonadal sites (three sacrococcyx, two thoracic, one extradural). Total or subtotal removal of primary tumor was carried out in nine patients at diagnosis and two others after some chemotherapy. Clinical complete remission (CR) was achieved in nine of ten patients with measurable disease and serum markers returned to normal in all 13 patients. Eleven remain disease-free 17 to 48 months (median, 28 months) after diagnosis. One patient (stage IV sacrococcygeal tumor) relapsed at the primary site 3 months after completing treatment, but is disease-free after further surgery, radiotherapy, and chemotherapy. Serial glomerular filtration rates were performed during treatment. Audiometry and pulmonary function tests were carried out where possible. Toxicity led to alteration of drug scheduling in two cases, but there were no permanent clinical renal, auditory, or pulmonary sequelae. These encouraging results confirm that MGCTs in children are as responsive as those in adults to cisplatin-containing chemotherapy and indicate that they may be as curable. The regimens are relatively well-tolerated and, with close monitoring, clinically significant toxicity should be avoidable.
Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas.
Authors: E C Borden, D A Amato, C Rosenbaum, H T Enterline, M J Shiraki, R H Creech, H J Lerner, P P Carbone
Journal: Journal of Clinical Oncology (1987)

This study addressed two major questions regarding therapeutic use of Adriamycin ([Adr] Adria Laboratories, Columbus, OH) in adult soft tissue sarcomas: the influence of dosing schedule and the value of adding imidazole carboxamide (DTIC) to Adr. Patients with objectively measurable metastatic soft tissue sarcomas were randomized to Adr 70 mg/m2 intravenously (IV) day 1 and every 3 weeks (94 patients); Adr 20 mg/m2 IV day 1, 2, and 3, and 15 mg/m2 IV day 8 and weekly thereafter (89 patients); and Adr 60 mg/m2 IV day 1 and DTIC 250 mg/m2 days 1 to 5, repeated every 3 weeks (92 patients). The regimens using Adr as a single agent resulted in an equivalent response frequency (18% and 16%) and survival (median, 8.0 and 8.4 months). DTIC significantly increased (P less than .02) the overall response frequency of Adr to 30%. However, DTIC did not influence survival (median, 8.0 months) or increase the number of complete responses. The toxicities of the two single-agent regimens differed: Adr weekly resulted in more stomatitis (P = .09) and less hematologic toxicity (P less than .05). DTIC resulted in substantially increased toxicity, primarily gastrointestinal (P less than .002); overall, 98% of patients receiving Adr-DTIC experienced moderate or worse toxicity. To decrease the potential for error in interpretation of treatment results, histopathological confirmation of diagnosis was undertaken by a panel of reference pathologists; pathology slides were submitted on 97% of entered patients. The on-study clinical diagnosis was affirmed in 199 of 316 patients (63%) with a final review. In 23% of patients, the panel agreed with the diagnosis of soft tissue sarcoma, but not with the type. In 14%, the panel concluded that a diagnosis of mesenchymal malignancy could not be affirmed. Final treatment results were based on the 275 pathologically confirmed, eligible patients. The most common histological subtype entered was leiomyosarcoma (99 patients). The response to Adr-DTIC of this subtype was higher (44%) than that of any other subtype. However, this difference alone was not responsible for the overall superiority of the combination. This confirmed that the combination of DTIC plus Adr adds to the response rate of Adr alone in soft tissue sarcomas. Whether the increased response frequency, without an impact on survival, is worth the significantly greater toxicity remains a subjective judgement that must be made within the context of the individual patient.
Introducing complementary medicine into the medical curriculum
Authors: Hagen Rampes, Fiona Sharples, Sarah Maragh, Peter Fisher
Journal: Journal of the Royal Society of Medicine (1997)

We surveyed the deans of British medical schools to determine the provision of complementary medicine in the undergraduate curriculum. We also sampled medical students at one British medical school to determine their knowledge of, and views on instruction in, complementary medicine. There is little education in complementary medicine at British medical schools, but it is an area of active curriculum development. Students' levels of knowledge vary widely between different therapies. Most medical students would like to learn about acupuncture, hypnosis, homoeopathy and osteopathy. We conclude that complementary medicine should be included in the medical undergraduate curriculum. This could be done without a great increase in teaching of facts, and could serve as a vehicle to introduce broader issues, as recommended by the General Medical Council.