tbuckley/cabot-search huggingface dataset:
Activation of mouse lymphocytes by anti-immunoglobulin. II. A thymus-independent response by a mature subset of B lymphocytes.
Authors: D G Sieckmann, I Scher, R Asofsky, D E Mosier, W E Paul
Journal: The Journal of Experimental Medicine (1978)

Mouse spleen cells can be stimulated to proliferate in vitro by purified anti-mu or anti-gamma,kappa antibodies. These responses can be obtained in cell populations bearing membrane immunoglobulin (Ig), purified by the fluorescence activated cell sorter (FACS), but they are not observed in FACS-purified Ig- cell populations. Furthermore, treatment of spleen cell populations with anti-Thy 1.2 and complement does not impair the response, nor does addition of nylon wool-purified T lymphocytes enhance it. These results indicate that B lymphocytes respond to anti-Ig and that their response does not require T cells. On the other hand, cells from athymic nude (nu/nu) mice respond slightly less well to anti-mu than do cells from heterozygous littermate (nu/+) controls; nu/nu cells are almost unresponsive to anti-gamm,kappa and addition of nylon wool-purified T cells from nu/+ controls does not restore the response. This suggests that T lymphocytes or the thymus may control the appearance of cells responsive to anti-gamma,kappa. Responsiveness of normal mice to anti-mu does not appear until 4 wk of age and does not reach maximum levels until 8 wk of age. Acquisition of full responsiveness to anti-gamma,kappa is even more delayed. This, together with the failure of mice with the CBA/N B-cell defect to respond to anti-Ig, suggests that cells stimulated to proliferate by anti-Ig are a mature subset of B cells. Depletion of adherent cells by Sephadex G-10 treatment or by treatment with carbonyl iron and exposure to a magnetic field does not diminish anti-mu or anti-gamma,kappa responses, suggesting that the responsiveness does not require the presence of macrophages. Thus, activation of B-cell proliferation by anti-Ig appears to be a T-cell independent, macrophage-independent process in which membrane Ig plays a direct role in signal generation.
<i>In vivo</i>regulation of inducible NO synthase in immune-mediated liver injury in mice
Authors: Kerstin Koerber, Gabriele Sass, Alexandra K. Kiemer, Angelika M. Vollmar, Gisa Tiegs
Journal: Hepatology (2002)

Inducible nitric oxide synthase (iNOS) has been shown to play an important role in the development of liver injury. iNOS deficiency protects mice from hemorrhage/resuscitation as well as from cytokine-mediated liver injury, for example, after administration of concanavalin A (con A). Here we investigated the in vivo effects of tumor necrosis factor (TNF)-α and/or interferon (IFN)-γ, two mediators of con A-induced liver injury, the TNF receptor (TNFR) usage leading to iNOS expression, and its connection with nuclear factor κB (NF-κB) activation. In conclusion, iNOS expression in vivo is dependent on both TNF-α and IFN-γ. Although con A-induced liver injury depends on both TNFR1 and TNFR2, TNF-dependent iNOS expression is mediated exclusively by TNFR1 and requires NF-κB activation.
Pharmacokinetic (PK) Interactions between Lapatinib (L) and Vinorelbine (VNR) in a Phase I Study in Locally Advanced or Metastatic Breast Cancer (LAMBC) Patients(Pts) Overexpressing HER2. GEP-01 – A Study of the FNCLCC-Group of Early Phase Trials.
Authors: F. Lokiec, E. Brain, N. Isambert, F. Dalenc, P. Tresca, J. Bonneterre, K. Rezaï, H. Roché, N. Penel, M. Jimenez, V. Diéras, P. Fumoleau
Journal: Cancer Research (2009)

Abstract Background: Lapatinib is effective in overexpressing HER2 LAMBC pts. Following anthracyclines, taxanes and capecitabine, VNR is an active agent in metastatic setting. Both drugs use the same main metabolic pathway: Cytochrome P450 3A4. We investigated the combination of L + VNR, seeking the recommended dose for further phase II studies, and looking for the PK interactions between the 2 drugs.Methods: Women with HER2+ LAMBC, in progression after ≤ 2 lines of trastuzumab-based treatment were treated with a 7 day (D-7 to D0) loading dose of L before starting VNR on a D1 and D8 q3w iv regimen. L was given po continuously. G-CSF as primary prophylaxis of febrile neutropenia (FN) was not permitted. Dose levels (DL) (L mg/VNR mg/m²) ranged from 750/20 to 1250/30 with 3 patients per DL. PK samples were collected on 7 points on D1 of cycle 1 for L and VNR dosages. PK time points analysis was performed on plasma for L and whole blood for VNR. For both drugs the analytical method was Ultra Performance Liquid Chromatography (UPLC) coupled with tandem mass spectrometry (MS-MS) as detection. VNR PK parameters were estimated by nonlinear mixed effect modeling (NONMEM) and L PK parameters were estimated by non compartmental software (MicroPharm).Results: Seventeen pts and 68 PK time points were available for VNR analysis. VNR was ascribed to a tri-compartment model. When considering all VNR data together, VNR clearance (CL) was 37.8±16.7 L/h, while it showed a gradual decrease according to specific dose of L: 47.5±20.4 L/h for L 750 mg (3 patients) vs 35.6±4.3 L/h for pooled data for L 1000 and 1250 (14 patients). This trend was not significant likely due to low number of patients treated at lower dose of L, while no significant difference was observed between L 1000 and L 1250. The mean elimination half life time (t1/2) of VNR was 0.12 h. Six patients and 42 PK time points were analyzed for L. L CL were respectively 83.8 ± 41.3 and 57.1 ± 5.5 L/h for patients who received 750 mg (3 patients) and 1000 mg (3 patients) of L with 20 mg of VNR. The mean elimination half life time (t1/2) of L was 2.89 h.Conclusions: A potential PK interference occurred between VNR and L. When the dose of L increased, both VNR and L CL decreased, likely due to CYP450-3A4 interactions. This trend should be confirmed by the PK analysis of L and VNR in more patients, including an intermediate DL (1250/22.5) still ongoing. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5091.
Method of Choice
Authors: Frank Cole
Journal: JAMA (1977)

Recently I read two articles that dealt with selection of anesthesia for one particular operation; each author called his system "the method of choice." The two methods were different: one author prescribed three or four agents; the other, five. I have done the same thing (just as well, I think) with one or two agents. Why each author called his technique a "method of choice" was hazy; both claimed to provide good operating conditions, and that was all. Neither paper offered statistical comparisons with other methods or counting of cases; nothing that might have been measured was measured. Clearly, the words "method of choice" had no justification, serving only to irritate the reader. There are few methods of choice, unless laid down in documented studies by serious workers. The use of the words "method of choice" without statistical study and proved significance, and without justification, is deplorable. All too often,
CLINICAL EXPERIENCE WITH ANTITOXIN IN PRIVATE AND HOSPITAL PRACTICE IN THE TREATMENT OF DIPHTHERIA—(ALL FORMS).
Authors: LOUIS FISCHER
Journal: JAMA (1895)

My first successful case with antitoxin was published in the<i>New York Medical Record</i>, Oct. 6, 1894, in which a child 11 years old was attended by Dr. Gerlach. In this case I injected 5 ccm. of Aronson's antitoxin between the shoulder blades. The child was discharged, cured, on the fourth day. This patient was presented before the New York Post-Graduate Clinical Society at its first meeting in the Hospital Building in October. Since then I have published a series of papers, embodying various clinical experiences; notably, however, papers that appeared on Nov. 17, 894, in the<i>New York Medical Record.</i>A series of thirty-six cases, which were attended by me, was published in the January number of the<i>American Journal of Medical Sciences</i>, wherein I reported a very successful list of cases. My percentage of deaths was but 5.8 per cent. The antitoxin used was brought over by me
Hypothyroidism: Diversity of Presentation
Authors: MICHAEL L. TACHMAN, GORDON P. GUTHRIE
Journal: Endocrine Reviews (1984)

HYPOTHYROIDISM is usually represented as having stereotyped, easily recognized signs and symptoms (1–4). Lethargy, constipation, cold intolerance, intellectual and motor dullness, dry skin, hoarse voice, slowed reflexes, and bradycardia are considered to be typical symptoms. Other features associated with the disease are usually given less emphasis. In our experience and that of others (5), the assumption that hypothyroidism has a typical presentation can be hazardous. Hypothyroidism is a common disease in adults. A recent survey (3) indicated that 1.4% of women (and 0.1% of men) are hypothyroid. This implies that appreciable numbers of patients may have uncommon symptoms overlooked by their physicians. One review of 400 cases (6) indicated that most of the above mentioned symptoms of hypothyroidism are present in only 25-70% of patients. Yet, most had some signs and symptoms, which if recognized as indicative of hypothyroidism, could have led to more prompt diagnosis and treatment. Also to be noted is that death from myxedema although uncommon does occur (7).
Abstract 3271: The association between germline genetic variants in the PI3K-AKT-mTOR pathway and breast cancer disease free survival
Authors: Mala Pande, Melissa Bondy, Kim-Anh Do, Aysegul A. Sahin, Jun Ying, Gordon B. Mills, Patricia Thompson, Abenaa Brewster
Journal: Cancer Research (2014)

Abstract Background: PI3K-AKT-mTOR pathway activation in breast tumors is associated with poorer breast cancer disease-free survival and decreased responsiveness to tamoxifen and trastuzumab. However, the role of germline variation in this pathway and breast cancer outcomes has not been previously evaluated. We hypothesized that single nucleotide polymorphisms (SNPs) in candidate genes affecting the PI3K-AKT-mTOR signaling pathway may act as genetic modifiers of breast cancer specific outcomes in patients diagnosed with early stage disease. Methods: We genotyped 106 SNPs in 13 genes (ADIPOQ, IGF1, INS, IRS1, LEP, LEPR, LEPROT, PIK3CA, PIK3R5, PTEN, TSC1, TSC2, and AKT1) in the P13K-AKT-mTOR pathway in a sample of 1020 women with stages I-II breast cancer treated at the MD Anderson Cancer Center between 1985 and 1999 and for whom long term follow-up on recurrence and death were available. The relationship between SNPs and breast cancer disease free survival (DFS) was assessed using Cox regression analysis. After correcting for false discovery rate (0.10) SNPs significantly associated with DFS in any genetic model (additive, dominant or recessive) were included in multivariable analysis. Results: After adjusting for race, age at diagnosis, tumor stage and treatment, rs1063539 in ADIPOQ (Hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.19 - 0.86), rs11585329 in LEPROT (HR 0.72, 95% CI 0.53 - 0.98), and rs2519757 in TSC1 (HR 0.29, 95% CI 0.09 - 0.91) were associated with improved DFS and rs1520220 in IGF1 (HR 1.56, 95% CI 1.21 - 2.00) and rs2677760 in PIK3CA (HR 1.43, 95% CI 1.70 - 1.92) were associated with worse DFS. The associations were not modified by type of systemic treatment received. The SNPs were not associated with tumor characteristics such as tumor size, lymph node status, nuclear grade, or hormone receptor status. Conclusion: In this study, germline allelic variation inthe PI3K-AKT-mTOR pathway appears to modify breast cancer patient outcomes. Future studies are needed to replicate our results and to evaluate the relationship between these polymorphisms and activation of the PI3K-AKT-mTOR pathway in breast tumors. Citation Format: Mala Pande, Melissa Bondy, Kim-Anh Do, Aysegul A. Sahin, Jun Ying, Gordon B. Mills, Patricia Thompson, Abenaa Brewster. The association between germline genetic variants in the PI3K-AKT-mTOR pathway and breast cancer disease free survival. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3271. doi:10.1158/1538-7445.AM2014-3271
Abstract A71: TMPRSS4 proteolytically activates pro-uPA to induce cancer cell invasion
Authors: Hye-Jin Min, Semi Kim
Journal: Cancer Research (2015)

Abstract The invasive nature of tumor cells is critical for cancer metastasis. Urokinase-type plasminogen activator (uPA), which is usually derived from stromal cells, is a well-known serine protease involved in invasion and metastasis. uPA is produced as an inactive single-chain protein (known as pro-uPA or sc-uPA) that is processed into the active disulfide-linked two-chain form of uPA by a proteolytic event. TMPRSS4 is a novel type II transmembrane serine protease that is highly expressed on the cell surface in pancreatic, thyroid, colon, and other cancer tissues. Previously, we demonstrated that TMPRSS4 mediates colorectal tumor cell invasion, migration, and metastasis and increased TMPRSS4 expression is associated with colorectal cancer progression. We also demonstrated that TMPRSS4 upregulates uPA gene expression through c-Jun N-terminal kinase signaling activation to induce cancer cell invasion. However, it remains unknown how proteolytic activity of TMPRSS4 contributes to invasion. Here, we report that TMPRSS4 directly converted inactive pro-uPA into the active form through its proteolytic activity. Analysis of conditioned medium from cells overexpressing TMPRSS4 demonstrated that the active TMPRSS4 protease domain is released from the cells and is associated with the plasma membrane. Furthermore, TMPRSS4 could increase pro-uPA-mediated invasion in a serine proteolytic activity-dependent manner. These observations suggest that TMPRSS4 is an upstream regulator of invasion through the regulation of uPA. This study provides valuable insights into the proteolytic function of TMPRSS4 as well as mechanisms for the control of invasion. Citation Format: Hye-Jin Min, Semi Kim. TMPRSS4 proteolytically activates pro-uPA to induce cancer cell invasion. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A71. doi:10.1158/1538-7445.CHTME14-A71
EFFECT OF HEPARIN ADMINISTRATION ON METABOLOMIC PROFILES FROM SAMPLES OBTAINED DURING CARDIAC CATHETERIZATION
Authors: Michael P. Brunner, Svati H. Shah, Damian M. Craig, James R. Bain, Michael J. Muehlbauer, Christopher B. Newgard, William E. Kraus, Christopher B. Granger, Michael H. Sketch, L. Kristin Newby
Journal: Journal of the American College of Cardiology (2011)
Responsiveness to Cetuximab without Mutations in<i>EGFR</i>
Authors: Zenta Tsuchihashi, Shirin Khambata-Ford, Nasser Hanna, Pasi A. Jänne
Journal: New England Journal of Medicine (2005)

T790M mutation was shown to confer resistance to gefitinib after it was introduced into the sequence of the wild-type EGFR and L858R mutant EGFR in vitro. 2,3 The T790M mutation results in steric hindrance of binding of gefitinib to the ATPkinase-binding pocket.The T790M mutation may cause acquired resistance to gefitinib. 2,3Our patient had concomitant T790M and L858R EGFR mutations in the original lung-biopsy specimen and showed primary resistance to gefitinib -a finding implying that a mutation in the T790M kinase domain can occur during the natural evolution of lung cancer.T790M mutant gefitinibresistant clones may preexist at levels below the threshold of detection 5 in some patients with lung cancer at presentation and then may expand selectively under gefitinib treatment, leading to the failure of gefitinib therapy.
Prevalence of cervical pathogens in women with and without inflammatory changes on smear testing.
Authors: W L Parsons, M Godwin, C Robbins, R Butler
Journal: BMJ (1993)

To assess correlation between nonspecific cervicitis, inflammation, or exudate on cervical smears tests and confirmed presence of known cervical pathogens.Investigation of women attending a family practice clinic for smear test by microbiological screening for Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Trichomonas vaginalis, Candida species, group B streptococcus, Gardnerella vaginalis, and Neisseria gonorrhoeae.Family practice teaching clinic in a university hospital.411 women presenting for a smear test.Prevalence of genital infections associated with presence or absence of inflammatory changes on cervical smear.Of the 132 women with inflammatory changes on cervical smear, 64 (48%) had positive cultures. Of the 248 without inflammatory changes, 117 (47%) had positive cultures. Subgroup analysis on individual organisms also showed no significant difference between the two groups.Reports of inflammatory changes on cervical smear testing are a poor indicator of infection.
Vitamin B6 dependency in homocystinuria.
Authors: G E Gaull, J A Sturman
Journal: BMJ (1971)

<h3>ABSTRACT</h3> Listening to self-chosen, pleasant and relaxing music reduces pain in fibromyalgia (FM), a chronic central pain condition. However, the neural correlates of this effect are fairly unknown and could be regarded as a more direct measure of analgesia. In our study, we wished to investigate the neural correlates of music-induced analgesia (MIA) in fibromyalgia patients. To do this, we studied 20 FM patients and 20 matched healthy controls (HC) acquiring rs-fMRI with a 3T MRI scanner, and pain data before and after two 5-min auditory conditions: music and noise. We performed resting state functional connectivity (rs-FC) seed-based correlation analyses (SCA) using pain and analgesia-related ROIs to determine the effects before and after the music intervention in FM and HC, and its correlation with pain reports. We found significant differences in baseline rs-FC between FM and HC. Both groups showed changes in rs-FC in several ROIs after the music condition between different areas, that were left lateralized in FM and right lateralized in HC. FM patients reported MIA that was significantly correlated with rs-FC decrease between the angular gyrus, posterior cingulate cortex and precuneus, and rs-FC increase between amygdala and middle frontal gyrus. These areas are related to autobiographical and limbic processes, and auditory attention, suggesting MIA may arise as a consequence of top-down modulation, probably originated by distraction, relaxation, positive emotion, or a combination of these mechanisms.
Impaired allergy diagnostics among parasite-infected patients caused by IgE antibodies to the carbohydrate epitope galactose-α1,3-galactose
Authors: Kurt Arkestål, Elopy Sibanda, Cecilia Thors, Marita Troye-Blomberg, Takafira Mduluza, Rudolf Valenta, Hans Grönlund, Marianne van Hage
Journal: Journal of Allergy and Clinical Immunology (2011)
Sympathoexcitation by Oxidative Stress in the Brain Mediates Arterial Pressure Elevation in Obesity-Induced Hypertension
Authors: Ai Nagae, Megumi Fujita, Hiroo Kawarazaki, Hiromitsu Matsui, Katsuyuki Ando, Toshiro Fujita
Journal: Circulation (2009)

Obesity is one of the major risk factors for cardiovascular disease and is often associated with increased oxidative stress and sympathoexcitation. We have already suggested that increased oxidative stress in the brain modulates the sympathetic regulation of arterial pressure in salt-sensitive hypertension, which is often associated with obesity. The present study was performed to determine whether oxidative stress could mediate central sympathoexcitation in the initial stage of obesity-induced hypertension.Four-week-old male Sprague-Dawley rats were fed a high-fat (45% kcal as fat) or low-fat (10% kcal as fat) diet for 6 weeks. Fat loading elicited hypertension and sympathoexcitation, along with visceral obesity. In urethane-anesthetized and artificially ventilated rats, arterial pressure and renal sympathetic nerve activity decreased in a dose-dependent fashion when 53 or 105 mumol/kg tempol, a membrane-permeable superoxide dismutase mimetic, was infused into the lateral cerebral ventricle. Central tempol reduced arterial pressure and renal sympathetic nerve activity to a significantly greater extent in high-fat diet-fed hypertensive rats than in low-fat diet-fed normotensive rats. Intracerebroventricular apocynin or diphenyleneiodonium, a reduced NADPH oxidase inhibitor, also elicited markedly greater reductions in arterial pressure and renal sympathetic nerve activity in the high-fat diet-fed rats. In addition, fat loading increased NADPH oxidase activity and NADPH oxidase subunit p22(phox), p47(phox), and gp91(phox) mRNA expression in the hypothalamus.In obesity-induced hypertension, increased oxidative stress in the brain, possibly via activation of NADPH oxidase, may contribute to the progression of hypertension through central sympathoexcitation.
Porphyria Cutanea Tarda in Relapse: A Case Report
Authors: R. J. Calvert, C. Rimington
Journal: BMJ (1953)

The relative frequency of the various types of porphyria (Waldenstrom, 1937;Watson, 1951) is calculable only from observation upon large series.Watson and colleagues (1951), reporting 88 cases of porphyria, observed over a 14-year period, found only 5 patients with con- genital porphyria, 10 with "mixed " (cutanea tarda) porphyria, and 73 with acute porphyria.Nevertheless, porphyria cutanea tarda may be much more common than is supposed (Macgregor, Nicholas, and Rimington, 1952;Wells and Rimington, 1953), since "attacks " or exacerbations may closely simulate those of acute porphyria; unless a stool porphyrin determination is carried out during remission, a distinction is at times hardly possible.The finding of normal urinary porphyrin in a patient seen only in the remission phase might lead to the exclusion altogether of porphyria from the diagnosis, but a stool porphyrin determination will always reveal the excessive total porphyrin excretion.Increased vigilance in dermatological case material might be rewarding.Brunsting and associates (1951) referred to 21 cases of the adult form of chronic porphyria with cuLtaneous manifestations seen at the Mayo Clinic in the previous six years.The case described below was first seen during the course of an attack, and only on one day were porphobilinogen and uroporphyrin present in the urine, although both coproporphyrin and protoporphyrin were regularly present in considerable amount.As the attack subsided, the faecal porphyrin rose and urinary porphyrin diminished.Case Report A.mechanic aged 26 was admitted as a surgical case to Whipps Cross Hospital on March 12, 1952.His chief com- plaints were central abdominal colic, frequent vomiting, and
Discordant Uptake of Tc-99m DTPA-Galactosyl Human Serum Albumin and Tc-99m Sn Colloid in a Patient With Severe Acute Hepatitis
Authors: CHIHOKO MIYAZAKI, TAKASHI MATSUNAGA, KOHZOH KUBO
Journal: Clinical Nuclear Medicine (1994)

A patient with recently diagnosed severe acute hepatitis underwent serial liver scintigraphy with Tc-99m Sn colloid and Tc-99m DTPA-galactosyl human serum albumin. In Initial studies, radionuclide distribution on Tc-99m DTPA-galactosyl human serum albumin scintigraphy was completely discrepant to that on Tc-99m Sn colloid scintigraphy. In a follow-up study 1 month later, the distribution of both radionuclides in the liver appeared relatively homogeneous. The uptake of Tc-99m DTPA-galactosyl human serum albumin and Tc-99m Sn colloid reflects the function of hepatocytes and Kupffer cells, respectively. Both kinds of scintigraphic study may be helpful to assess histopathologic change of different hepatic tissue architectures.