tbuckley/cabot-search huggingface dataset:
Large Dorsal Tumour Removed to Relieve Dyspn a and Cardiac Distress
Authors: J. W. Cousins
Journal: BMJ (1884)

_,.[V%bid X8 >W.1,188.!] botiseqt'e of thf!tisof(eiss) thet -"e1~in thzacpuhe; 'Xi64bes--*as r#senst' E in4'ae 'The intensity of the disease was greatest in the foretr3 ¢l &bne U,hmi in the hlimeri; &nd -te Pmora iffj±ea .*he aii no !fiarrhcea.The spleen was enldtge&d<nthree caos."imia -tI -maeisti6n :were marked in all.pyre2xia wag -observ3d io un- 0iWa t edc' es.The urine did not iho* aany increas Of of eartiyr -"4w ooifse of the disease was chronie,; and1a ted bin'lzy-mOnths.-D `occirred in two cases in consequence of difsebhitis in -4AW id br6nhopneunonia in the other.Wi{fhiegaid to etilogy, all iW"easeg occured during the fiislttwo years, aid Athe 4i^se-Vepb-n ilOth fitt'year.They Were all femalbs.Th,-food Was; 'ih alf pro-: %bsbillty, poor in phOsphoric acid and 1ilie.-Noheeditary influ'ence -ld'be traced, and rn evidence of heteditary syphilis.i The disease 6 'be diagnosed, Dr. Rehn saysA first, from 'co0nHe*ital yphilis, ;eondly, from-rickets; the softening of bone-that' ometimes occurs in syphilis being associated with other indications of the presence of the disease, is easily recognised.He finds the following differ- ences from rickets:
Protective Action of Methylprednisolone on the Myocardium during Experimental Myocardial Ischemia in the Cat
Authors: JAMES A. SPATH, DAVID L. LANE, ALLAN M. LEFER
Journal: Circulation Research (1974)

Cats subjected to coronary artery occlusion were used to study the effect of methylprednisolone on the release of lysosomal acid hydrolases and creatine phosphokinase (CPK) from ischemic myocardial tissue. Plasma CPK activity was increased significantly 2 hours after occlusion and increased eightfold 5 hours after ligation in vehicle-treated cats. Intravenous administration of methylprednisolone (30 mg/kg) 30 minutes before or 60 minutes after occlusion significantly limited the increases in plasma CPK activity to values only slightly greater than those observed in sham-operated cats. Plasma activities of the lysosomal hydrolases, β-glucuronidase and cathepsin D, were comparable in all groups of cats and did not change during the 5-hour observation period. Nevertheless, cathepsin D and β-glucuronidase activities were reduced 41% and 33%, respectively, in the ischemic portion of the myocardium of untreated cats subjected to coronary artery ligation. The CPK activity of the ischemic myocardium was reduced 43% in these cats. Pre- or posttreatment of cats with methylprednisolone prevented the decline in CPK and lysosomal hydrolase activity of ischemic myocardium. These data indicate that lysosomal disruption is a consequence of myocardial ischemia and that pre- or posttreatment with methylprednisolone prevents the leakage of myocardial lysosomal and cellular enzymes. Moreover, the methylprednisolone-induced stabilization of myocardial membranes appears to be related to the ability of glucocorticoid to limit infarct size following myocardial ischemia.
Successful treatment of severe thrombotic thrombocytopenic purpura with the monoclonal antibody rituximab
Authors: Jens Chemnitz, Andreas Draube, Christof Scheid, Peter Staib, Armin Schulz, Volker Diehl, Dietmar Söhngen
Journal: American Journal of Hematology (2002)

Abstract The only established treatment for patients with thrombotic thrombocytopenic purpura (TTP) is plasma exchange against fresh frozen plasma. For cases refractory to plasma exchange, no generally treatment schedule exists. One option is immunosuppressive therapy with corticosteroids and vincristine. Rituximab is a chimeric monoclonal antibody directed against the CD20 antigen, and it has been successfully used in B‐cell malignancies and is being investigated in autoimmune diseases. Its efficacy in TTP has not yet been determined. We report two female patients with severe TTP refractory to multiple courses of plasmapheresis, high‐dose steroid treatment, and vincristine who responded after adding rituximab while continuing plasmapheresis. Am. J. Hematol. 71:105–108, 2002. © 2002 Wiley‐Liss, Inc.
Approaches to Cardiovascular Disease and Its Treatment
Authors: Zachary T Bloomgarden
Journal: Diabetes Care (2003)

This is the third of a series of articles reviewing presentations at the 63rd annual scientific session of the American Diabetes Association (ADA), held in New Orleans, Louisiana, June 2003.

Barbara Howard (Hyattsville, MD) gave the Kelley West lecture, in which she discussed the Strong Heart Study and the relationship between diabetes and cardiovascular disease (CVD). The study, which began in 1988 in three American Indian communities, describes “the epidemic of CVD and diabetes among this population.” A total of 4,549 individuals age 45–74 years of age living in the Hela River Indian reservation in Arizona, including Pima, Sioux, and Dakota Indians, were studied with examinations at 5-year intervals and ongoing yearly surveillance of CVD mortality and events. Comparing the study population with their counterparts in the general populations of North and South Dakota, Arizona, and Oklahoma, levels of total and CVD mortality are ∼2-fold higher among women and 1.5-fold higher among men. Similarly, carotid ultrasound studies show increased atherosclerosis among Indian men and women compared with other populations. There also appear to be trends to increasing CVD rates over the decade of the study.

Diabetes is very prevalent among American Indian communities. In the Strong Heart Study, rates exceed 60% in Arizona and 40% in the Oklahoma and Dakota groups. At 8-year follow-up, CVD rates are markedly increased among people with diabetes; coronary heart disease (CHD) risks are eight- and threefold higher among women and men with diabetes, respectively. If, as Howard suggested, CVD takes 15–20 years to develop, one would expect a lag time of approximately this duration between the development of diabetes and that of CVD. This appears to be the case in the studied population, suggesting that the current epidemic of diabetes in the U.S. population will result in an increase in CVD rates, reversing current …
The calculation of actual or received dose intensity: a comparison of published methods.
Authors: D L Longo, P L Duffey, V T DeVita, M N Wesley, S M Hubbard, R C Young
Journal: Journal of Clinical Oncology (1991)

Two recent reports of the same combination chemotherapy program, cyclophosphamide, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, bleomycin, and prednisone (ProMACE-CytaBOM), in similar subsets of patients with advanced-stage aggressive-histology lymphoma used two different methods to report the actual dose-intensity (DI) data. One method treats DI as a property of a particular cycle of treatment within the entire population that received that cycle. The other treats DI as a characteristic of a particular patient's entire treatment course. We have applied both methods to the same set of data and provide evidence that the latter method is preferable for at least two reasons: (1) it more accurately reflects actual DI by clearly incorporating the duration of the actual treatment course and, thus, can be used to compare the administration of same or related regimens to distinct patient populations; and (2) it allows assignment of a numerical value to an individual patient's treatment course or a group of patients' treatment courses such that DI can be examined for its impact on treatment outcome just like any other prognostic factor. The observed differences in treatment outcome between the Southwest Oncology Group (SWOG) and National Cancer Institute (NCI) studies are not clearly related to differences in distribution of clinical prognostic factors in the two study populations. The differences in methods of reporting DI prohibit evaluation of the influence of dose-related variables on outcome in the two studies. Adoption of a standard method of calculating and reporting DI data would facilitate evaluation of the prognostic significance of DI.
Modulation of Genetic and Epigenetic Biomarkers of Colorectal Cancer in Humans by Black Raspberries: A Phase I Pilot Study
Authors: Li-Shu Wang, Mark Arnold, Yi-Wen Huang, Christine Sardo, Claire Seguin, Edward Martin, Tim H.-M. Huang, Ken Riedl, Steven Schwartz, Wendy Frankel, Dennis Pearl, Yiqing Xu, John Winston, Guang-Yu Yang, Gary Stoner
Journal: Clinical Cancer Research (2010)

This study evaluated the effects of black raspberries (BRBs) on biomarkers of tumor development in the human colon and rectum including methylation of relevant tumor suppressor genes, cell proliferation, apoptosis, angiogenesis, and expression of Wnt pathway genes.Biopsies of adjacent normal tissues and colorectal adenocarcinomas were taken from 20 patients before and after oral consumption of BRB powder (60 g/d) for 1-9 weeks. Methylation status of promoter regions of five tumor suppressor genes was quantified. Protein expression of DNA methyltransferase 1 (DNMT1) and genes associated with cell proliferation, apoptosis, angiogenesis, and Wnt signaling were measured.The methylation of three Wnt inhibitors, SFRP2, SFRP5, and WIF1, upstream genes in Wnt pathway, and PAX6a, a developmental regulator, was modulated in a protective direction by BRBs in normal tissues and in colorectal tumors only in patients who received BRB treatment for an average of 4 weeks, but not in all 20 patients with 1-9 weeks of BRB treatment. This was associated with decreased expression of DNMT1. BRBs modulated expression of genes associated with Wnt pathway, proliferation, apoptosis, and angiogenesis in a protective direction.These data provide evidence of the ability of BRBs to demethylate tumor suppressor genes and to modulate other biomarkers of tumor development in the human colon and rectum. While demethylation of genes did not occur in colorectal tissues from all treated patients, the positive results with the secondary endpoints suggest that additional studies of BRBs for the prevention of colorectal cancer in humans now appear warranted.
A Study of the Mechanisms by Which Adrenocorticotropic Hormone Maintains Adrenal Steroidogenic Responsiveness*
Authors: Robert L. Ney, Richard N. Dexter, Warren W. Davis, Leonard D. Garren
Journal: Journal of Clinical Investigation (1967)

Following hypophysectomy in the rat, there was a progressive decline in the rate of adrenal protein synthesis in vivo during the ensuing 24-48 hr, and an accompanying decrease in the acute corticosterone secretory response to an intravenous injection of ACTH. There was a similar decrease in the in vitro conversion of Delta(5)-pregnenolone, progesterone, and deoxycorticosterone to corticosterone. These in vivo and in vitro effects of hypophysectomy could be reversed by the administration of depot ACTH for an additional 7 hr period. However, if cycloheximide, an inhibitor of protein synthesis, was administered concomitantly with the depot ACTH, then the restorative actions of ACTH on the steroid biosynthetic pathway were prevented. These experiments suggest that ACTH maintains not only the general structure of the adrenal cortex, but also the level of the steroid biosynthetic mechanism, through its effects on adrenal protein synthesis.
Targeted-bisulfite sequence analysis of the methylation of CpG islands in genes encoding PNPLA3, SAMM50, and PARVB of patients with non-alcoholic fatty liver disease
Authors: Takuya Kitamoto, Aya Kitamoto, Yuji Ogawa, Yasushi Honda, Kento Imajo, Satoru Saito, Masato Yoneda, Takahiro Nakamura, Atsushi Nakajima, Kikuko Hotta
Journal: Journal of Hepatology (2015)
Note on the Neurotic Origin of Lichen Planus
Authors: T. C. Fox
Journal: BMJ (1880)

swelling of the: leg and fever had then's 'ubsided, but therei wias still 'nerves to supplement that of the vaso-motor apparatus.Thirdly, I shall not press any ar-gumient (derival)e from tlhe groupinc of the papules or the habitat of the eruption, but I wvish to desciibe two cases where the papules were distributed in a maniner tie significance of which will be at once apparent.CASE I.--C., aged 50, a stout but active man, engaged in farming, 'hadl rhetumatic fever in 1876, but without heart-affection.Ile was left much debilitated, and, in April 187S, suffered from herpes preputialis.In JulY 1878, he had pains in his legs, aind was lame for soime timie but, on that condition disappearing, he sou,ght advice, inl Augf"ust 1878, for the outbreak of the eruiptioni of lichlen planus, which was most typical in character.Ile wvas excessively low-spirited, an(d in an exceedingly nervous state.The eruiption was Ilrmiited to tlhe region of the elbows, the back of the right thiah, and to a narrow band Albhich extended down the inner half of the front of the right thigh, on the inside of the knee, and, increasing in width on the inside of the calf, terminated just behind the internal malleolus.CASE iI was an almost preciscly similar case, seen also nearl)y at tie
Prevalence and Risk Factors for Urinary Incontinence in Overweight and Obese Diabetic Women
Authors: Suzanne Phelan, Alka M. Kanaya, Leslee L. Subak, Patricia E. Hogan, Mark A. Espeland, Rena R. Wing, Kathryn L. Burgio, Vicki DiLillo, Amy A. Gorin, Delia S. West, Jeanette S. Brown
Journal: Diabetes Care (2009)

OBJECTIVE To determine the prevalence and risk factors for urinary incontinence among different racial/ethnic groups of overweight and obese women with type 2 diabetes. RESEARCH DESIGN AND METHODS Cross-sectional analysis of baseline data from the Action for Health in Diabetes (Look AHEAD) study, a randomized clinical trial with 2,994 overweight/obese women with type 2 diabetes. RESULTS Weekly incontinence (27%) was reported more often than other diabetes-associated complications, including retinopathy (7.5%), microalbuminuria (2.2%), and neuropathy (1.5%). The prevalence of weekly incontinence was highest among non-Hispanic whites (32%) and lowest among African Americans (18%), and Asians (12%) (P &amp;lt; 0.001). Asian and African American women had lower odds of weekly incontinence compared with non-Hispanic whites (75 and 55% lower, respectively; P &amp;lt; 0.001). Women with a BMI of ≥35 kg/m2 had a higher odds of overall and stress incontinence (55–85% higher; P &amp;lt; 0.03) compared with that for nonobese women. Risk factors for overall incontinence, as well as for stress and urgency incontinence, included prior hysterectomy (40–80% increased risk; P &amp;lt; 0.01) and urinary tract infection in the prior year (55–90% increased risk; P &amp;lt; 0.001). CONCLUSIONS Among overweight and obese women with type 2 diabetes, urinary incontinence is highly prevalent and far exceeds the prevalence of other diabetes complications. Racial/ethnic differences in incontinence prevalence are similar to those in women without diabetes, affecting non-Hispanic whites more than Asians and African Americans. Increasing obesity (BMI ≥35 kg/m2) was the strongest modifiable risk factor for overall incontinence and stress incontinence in this diverse cohort.
Relation between Severity of the Disease and Arrhythmia Incidence in Patients with Psoriasis
Authors: Zakir Karadağ, Hatice Yıldız, Özgür Günebakmaz, Bahadır Şarlı, Mikail Yarlıoğlueş, Orhan Doğdu, İdris Ardıç, İbrahim Gül, Ali Doğan, Mehmet Güngör Kaya, Ali Ergin, Ekrem Aktaş
Journal: Journal of the American College of Cardiology (2013)
Deliberate self-poisoning with isotretinoin
Authors: N.C. Hepburn
Journal: British Journal of Dermatology (1990)

Journal Article Deliberate self‐poisoning with isotretinoin Get access N.C. Hepburn N.C. Hepburn Department of Dermatology, Cambridge Military Hospital, Aldershot, Hants GUII2AN, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 122, Issue 6, 1 June 1990, Page 840, https://doi.org/10.1111/j.1365-2133.1990.tb06279.x Published: 01 June 1990
Polymorphisms Associated With Circulating Sex Hormone Levels in Postmenopausal Women
Authors: A. M. Dunning, M. Dowsett, C. S. Healey, L. Tee, R. N. Luben, E. Folkerd, K. L. Novik, L. Kelemen, S. Ogata, P. D. P. Pharoah, D. F. Easton, N. E. Day, B. A. J. Ponder
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Reports suggest a relationship between circulating sex hormone levels and breast cancer risk, but genetic association studies have been inconclusive. We investigated the association between levels of sex hormones and single nucleotide polymorphisms (SNPs) in genes coding for the enzymes that regulate them. Methods: We assayed circulating levels of estradiol, testosterone, estrone, androstenedione, 17α-hydroxyprogesterone, and sex hormone–binding globulin (SHBG) in 1975 normal postmenopausal women. Fifteen SNPs in the CYP17, CYP19, EDH17B2, SHBG, COMT, and CYP1B1 genes were genotyped in these postmenopausal women and in a breast cancer case–control study. Associations of genotypes with breast cancer risk were evaluated in the case–control study and with hormone levels in the postmenopausal women using multiple linear regression with assay batch, body mass index, parity, peri- or postmenopausal status, and age band as covariates. Results: CYP19 SNPs (rs10046 and [TCT]+/−) were associated with differences in estradiol level ( P = .0006 and P = .0003, respectively) and the estradiol : testosterone ratio ( P = .000001 and P = .002). SNP rs10046 explained 1.6% of the variance ( r2 ) in the estradiol : testosterone ratio. SHBG SNPs (5′ untranslated region [5′UTR] g-a and D356N) were associated with both SHBG levels ( P <10 −6 and P = .005) and the estradiol : SHBG ratio ( P = .000008 and P = .01). These SNPs explained 2.4% and 0.6% of the variance in SHBG levels, respectively. SNPs in the other genes were not associated with differences in any hormone levels, and none were statistically significantly associated with breast cancer risk. Conclusion: Genetic variation in CYP19 and SHBG contributes to variance in circulating hormone levels between postmenopausal women, but low r2 values may explain why these genes have given inconclusive results in breast cancer case–control studies.
Histopathologic-Based Prognostic Factors of Colorectal Cancers Are Associated With the State of the Local Immune Reaction
Authors: Bernhard Mlecnik, Marie Tosolini, Amos Kirilovsky, Anne Berger, Gabriela Bindea, Tchao Meatchi, Patrick Bruneval, Zlatko Trajanoski, Wolf-Herman Fridman, Franck Pagès, Jérôme Galon
Journal: Journal of Clinical Oncology (2011)

Purpose The prognosis of patients with colorectal cancer has sometimes proved uncertain; thus, the prognostic significance of immune criteria was compared with that of the tumor extension criteria using the American Joint Committee on Cancer/International Union Against Cancer–TNM (AJCC/UICC-TNM) staging system. Patients and Methods We studied the intratumoral immune infiltrates in the center of the tumor and in the invasive margin of 599 specimens of stage I to IV colorectal cancers from two independent cohorts. We analyzed these findings in relation to the degree of tumor extension and to the frequency of recurrence. Results Growth of the primary tumor and metastatic spread were associated with decreased intratumoral immune T-cell densities. Sixty percent of patients with high densities of CD8 + cytotoxic T-lymphocyte infiltrate presented with stage Tis/T1 tumor, whereas no patients with low densities presented with such early-stage tumor. In patients who did not relapse, the density of CD8 infiltrates was inversely correlated with T stage. In contrast, in patients whose tumor recurred, the number of CD8 cells was low regardless of the T stage of the tumor. Univariate analysis showed that the immune score was significantly associated with differences in disease-free, disease-specific, and overall survival (hazard ratio [HR], 0.64, 0.60, and 0.70, respectively; P &lt; .005). Time-dependent receiver operating characteristic curve analysis illustrated the predictive accuracy of the immune parameters (c-index = 65.3%, time-dependent c-index [Cτ] = 66.5%). A final stepwise model for Cox multivariate analysis supports the advantage of the immune score (HR, 0.64; P &lt; .001; Cτ = 67.9%) compared with histopathologic features in predicting recurrence as well as survival. Conclusion Assessment of CD8 + cytotoxic T lymphocytes in combined tumor regions provides an indicator of tumor recurrence beyond that predicted by AJCC/UICC-TNM staging.
Mithramycin inhibits SP1 binding and selectively inhibits transcriptional activity of the dihydrofolate reductase gene in vitro and in vivo.
Authors: S W Blume, R C Snyder, R Ray, S Thomas, C A Koller, D M Miller
Journal: Journal of Clinical Investigation (1991)

The promoter of the human dihydrofolate reductase (DHFR) gene contains two consensus binding sites for the DNA binding protein Sp1. DNAse protection and gel mobility shift assays demonstrate binding of recombinant Sp1 to both decanucleotide Sp1 binding sequences which are located 49 and 14 base pairs upstream of the transcription start site. The more distal of the two binding sites exhibits a somewhat higher affinity for Sp1. The G-C specific DNA binding drug, mithramycin, binds to both consensus sequences and prevents subsequent Sp1 binding. Promoter-dependent in vitro transcription of a DHFR template is selectively inhibited by mithramycin when compared to the human H2b histone gene. A similar effect is also noted in vivo. Mithramycin treatment of MCF-7 human breast carcinoma cells containing an amplified DHFR gene induces selective inhibition of DHFR transcription initiation, resulting in a decline in DHFR mRNA level and enzyme activity. This selective inhibition of DHFR expression suggests that it is possible to modulate the overexpression of the DHFR gene in methotrexate resistant cells.
Pathogenic role for skin macrophages in a mouse model of keratinocyte-induced psoriasis-like skin inflammation
Authors: A. Stratis
Journal: Journal of Clinical Investigation (2006)

Psoriasis is a common skin disease, the pathogenesis of which has not yet been resolved. In mice, epidermis-specific deletion of inhibitor of NF-κB (IκB) kinase 2 (IKK2) results in a skin phenotype that mimics human psoriasis in several aspects. Like psoriasis, this skin disease shows pronounced improvement when mice are treated with a TNF-neutralizing agent. We have found previously that this phenotype does not depend on the presence of αβ T lymphocytes. In order to evaluate contributions of other immune cell populations to the skin disease, we selectively eliminated macrophages and granulocytes from the skin of mice with epidermis-specific deletion of IKK2 (K14-Cre-IKK2fl/fl mice). Elimination of skin macrophages by subcutaneous injection of clodronate liposomes was accompanied by inhibition of granulocyte migration into the skin and resulted in a dramatic attenuation of psoriasis-like skin changes. The hyperproliferative, inflammatory skin disease in K14-Cre-IKK2fl/fl mice was a direct consequence of the presence of macrophages in the skin, as targeted deletion of CD18, which prevented accumulation of granulocytes but not macrophages, did not lead to major changes in the phenotype. Targeted deletion of the receptor for IFN-γ revealed that the pathogenesis of the skin disease does not depend on classical IFN-γ–mediated macrophage activation. Our results demonstrate that in mice epidermal keratinocytes can initiate a hyperproliferative, inflammatory, IFN-γ–independent, psoriasis-like skin disease whose development requires essential contributions from skin macrophages but not from granulocytes or αβ T lymphocytes.