tbuckley/cabot-search huggingface dataset:
Macroglobulinemia and Hairy-Cell Leukemia
Authors: David W. Golde, Andrew Saxon, Ronald H. Stevens
Journal: New England Journal of Medicine (1977)

Leukemic reticuloendotheliosis, or hairy-cell leukemia, is a distinct clinical entity characterized by the proliferation of cells that have prominent cytoplasmic projections and contain the tartrate-resistant isozyme 5 of acid phosphatase.1 2 3 Although the clinical and morphologic features of this disease are widely known, there is considerable disagreement over whether the leukemic cell belongs to the lymphocyte or monocyte lineage.4 In the unusual case of hairy-cell leukemia reported below, the leukemic cells produced a monoclonal IgM, thereby substantiating the lymphocyte derivation of the neoplastic cells in this patient. The findings emphasize the wide clinical and biologic spectrum of B-cell neoplasms.Case History . . .
Clinical characterization of a family with a mutation in the uromodulin (Tamm-Horsfall glycoprotein) gene
Authors: Anthony J. Bleyer, Arch S. Woodard, Zak Shihabi, Jaspreet Sandhu, Honping Zhu, Scott G. Satko, Nelson Weller, Elizabeth Deterding, Debra Mcbride, Michael C. Gorry, Linda Xu, Deann Ganier, Thomas C. Hart
Journal: Kidney International (2003)
P01.01 * EXPRESSION OF FIBROBLAST ACTIVATION PROTEIN ALPHA IN HUMAN HIGH-GRADE GLIOMAS
Authors: E. Balaziova, P. Busek, M. Hilser, I. Vomelova, L. Sromova, E. Krepela, A. Sedo
Journal: Neuro-Oncology (2014)

Fibroblast activation protein alpha (FAP) is a dual specificity serine protease that is strongly associated with the development and progression of human carcinomas and represents a potential stromal target for anticancer treatment. Due to its gelatinolytic activity, FAP may participate in matrix-degradation, thus contributing to cell invasion. In addition, by its dipeptidyl peptidase enzymatic activity FAP was reported to efficiently hydrolyze several bioactive peptides relevant for cancer progression. However, relatively little is known about the expression and function of FAP in human astrocytic tumors. In our study, we detected higher FAP mRNA and protein expression in high-grade gliomas compared to controls (pharmacoresistant epilepsy). Using immunohistochemistry, we identified two different FAP+ cell subpopulations in gliomas. One comprised of dispersed cells intimately encircling the dysplastic vessels; these cells were negative for the glial and endothelia markers, but expressed the mesenchymal markers SMA, TEM-1 and the fibroblast antigen detected by the TE-7 antibody. Expression of these markers was maintained in FAP+ cells isolated and propagated in pericyte medium in vitro, further supporting their probable mesenchymal origin. The other FAP+ subpopulation was represented by GFAP+ parenchymal cells, part of which also expressed the transcription factor SOX-2, a marker of multipotent neural and glioma stem cells. In a mouse model, FAP was variably expressed by orthotopically implanted human glioma cells and was frequently induced in the host cells surrounding the tumors. To determine, whether FAP enzymatic activity may promote the malignant behavior of glioma cells, enzymatically active or mutant, enzymatically inactive human FAP were transfected into FAP negative glioma cells. Surprisingly, transgenic expression of wild type FAP decreased the migration and matrigel as well as collagen type I invasion of glioma cells. Moreover, transgenic wild type but not mutant, enzymatically inactive FAP negatively influenced adhesion and spreading on collagen I, but not fibronectin, which was associated with decreased focal adhesion formation and FAK phosphorylation. Nevertheless, tumor size was not affected by transgenic FAP in an orthotopic xenotransplantation mouse model. To summarize, FAP expression is increased in human glioblastomas due to its upregulation in the transformed glioma cells and/or stromal elements including perivascularly localized mesenchymal cells and possibly stromal glial cells. Introduction of FAP into glioma cells was not sufficient to promote their malignant behavior and tumor growth. Nevertheless, considering the selective expression of FAP in the glioblastoma microenvironment, FAP may represent a possible therapeutic target. Supported by the grants IGA12237-5/2011, PRVOUK-P27/LF1/1, UNCE204013, SVV260032/2014.
Intravascular oesophageal variceal pressure (IOVP) assessed by endoscopic fine needle puncture under basal conditions, Valsalva's manoeuvre and after glyceryltrinitrate application.
Authors: M Staritz, T Poralla, K H Meyer zum Buschenfelde
Journal: Gut (1985)

A simple and safe procedure providing sensitive and reproducible direct measurement of intravascular oesophageal variceal pressure (IOVP) during routine oesophagoscopy is described. The method requires only commercially available equipment. First results were obtained in 16 patients with oesophageal varices caused by liver cirrhosis (Child's A) can be summarised as follows: intravascular oesophageal variceal pressure was nearly identical in different varices of the single patient. Varices grade III exhibited a significantly higher intravascular oesophageal variceal pressure than varices grade II (22.7 +/- 2.5 vs 15.7 +/- 0.6 mmHg, p less than 0.05). After Valsalva's manoeuvre there was a remarkable increase in intravascular oesophageal variceal pressure by 13.6 +/- 1.0 mmHg irrespective of the variceal size. The high intravascular oesophageal variceal pressure values observed in grade III varices during the rise of the intraabdominal pressure may indicate an important risk factor for variceal haemorrhage. Glyceryltrinitrate (1.2 mg sprayed onto the tongues of 14 patients) very effectively lowered the intravascular oesophageal variceal pressure from 22.8 +/- 2.0 to 12.0 +/- 0.4 mmHg in grade III varices, and from 16.3 +/- 0.4 to 10.0 +/- 0.4 mmHg in grade II varices (p less than 0.005 in both groups). We conclude that this method provides a suitable tool to study the effect of drugs with presumed influence on the oesophageal variceal pressure and that the impressive effect of glyceryltrinitrate in lowering intravascular oesophageal variceal pressure warrants further study on the effect of longer acting nitrates on intravascular oesophageal variceal pressure, and the rebleeding rate after oesophageal variceal haemorrhage.
Bioethics and the Political Distortion of Biomedical Science
Authors: Elizabeth Blackburn
Journal: New England Journal of Medicine (2004)

In late September 2001, I was asked to serve on the President's Council on Bioethics. My initial instinct was not to accept, because I was concerned that the Bush Administration would not be interested in considering fully the potential of certain controversial advances in basic biomedical research. Indeed, the administration was already on record as opposing federal funding for somatic-cell nuclear transplantation and therapeutic cloning. (Therapeutic cloning involves making early-stage preimplantation embryos for use as sources of stem cells, whereas reproductive cloning is the creation of cloned babies through the transfer of cloned embryos into a woman's uterus.) Two factors, . . .
Needle exchange programmes should do more to prevent transmission of hepatitis C virus
Authors: C. Ford
Journal: BMJ (1996)

EDITOR,—The debate on whether asymptomatic people at high risk of hepatitis C should be screened shows that, whether we agree with screening or not, until more effective treatment becomes available the most appropriate strategy is prevention.1 The largest group of people who are at risk of hepatitis C are those who continue to inject drugs. Needle exchange programmes may …
Adhesion of Malignant Cells to Capillary Endothelium
Authors: Bernard Ecanow
Journal: JAMA (1977)

To the Editor.—  In a recent clinical report (235:2825, 1976), Li and Ross indicate that cells from solid tumors that escape into the general circulation either perish or remain dormant until they have achieved attachment to the endothelium of the capillary wall with the assistance of a fibrin clot. Our laboratory studies indicate this observation to be correct but incomplete.  The known adhesive properties of fibrin and its continuous presence in the blood make it a logical agent to bind the malignant cells to the endothelium walls. However, it is important to point out that the adhesiveness of fibrin is a function of its surface-active properties. Thus, we have observed that a number of endogenous surface-active molecules (such as lecithin), as well as macromolecules (such as the mucopolysaccharides and albumin), are also capable of adsorbing onto cell surfaces and forming films that adhere readily to adjacent surfaces. These surfaces can
Radioimmunoassay and Clearance of Circulating Dopamine-β-Hydroxylase
Authors: Robert A. Rush, Laurence B. Geffen
Journal: Circulation Research (1972)

Release of the enzyme dopamine-β-hydroxylase (DBH) into the circulation by activity of the sympathetic nervous system was demonstrated by enzymatic assay of serum DBH. The development of a sensitive and specific solid-phase radioimmunoassay suitable for routine assay of serum DBH is described. It is sensitive to 1 ng of purified sheep DBH and is reproducible with a coefficient of variation of 4%. The mean of serum values for five normal sheep was 0.59 ± 0.02 (SE) µg/ml. The assay was sufficiently sensitive to measure DBH in 10 µliters of human serum even though cross-reactivity with antibodies against sheep DBH was incomplete. Clearance of circulating DBH was measured by the decay of radioactivity due to 125 I-DBH after steady state intravenous infusion in lambs. The estimated half-life of circulating DBH after correction for labeled metabolites was approximately 3 hours, and it was cleared from blood at 250 ml/hour. Under resting conditions, the rate of release of DBH into the circulation was about 10 µg DBH/hour kg -1 body weight. The distribution of radioactivity in various organs 7 to 48 hours after infusion showed that only the kidneys, lungs, and liver were significantly labeled. Since circulating DBH does not appear to be selectively taken up by sympathetic nerves nor rapidly metabolized, radioimmunoassay of serum DBH may be useful in measuring sympathetic activity in a wide range of physiological and disease states.
The Human Rosette-Forming Cell as a Marker of a Population of Thymus-Derived Cells
Authors: Joseph Wybran, Martin C. Carr, H. Hugh Fudenberg
Journal: Journal of Clinical Investigation (1972)

Sheep red blood cells can surround, in vitro, some human peripheral blood lymphocytes in a formation called a rosette. The number of rosetteforming cells (RFC) in 50 normal persons had a wide range (4-40%). The organs of 13 human fetuses (11-19 wk conceptional age) were examined for the presence of RFC. The thymus possessed the highest percentage of RFC, the maximum being 65% of total thymocytes in two 15-16 wk fetal specimens. Blood RFC were always present and their number slightly increased in the oldest fetuses. The bone-marrow showed 0-8% in the six fetuses studied. RFC were found in the spleen around the 13th wk and in the liver around the 17th wk of gestation. These observations lead to the hypothesis that human blood RFC may be chiefly thymic derived. Studies of patients with immunological disorders support this hypothesis: one patient with Nezelof syndrome had no blood RFC and four patients with Wiskott-Aldrich syndrome had a low number of blood RFC (1 and 1.5%). Patients with acquired hypogammaglobulinemia showed a normal percentage of RFC. With the fetal thymocytes, the percentage of inhibition with anti-mu serum increased with the fetal age to become complete in the oldest fetuses studied. Incubation of the oldest fetal thymocytes or the blood lymphocytes with anti-gamma serum of anti-mu serum completely inhibited the rosette formation. These results suggest that mu-chain determinants are present on human fetal thymocytes and blood RFC. The significance of the presence of gamma-chain determinants on these cells is unclear.
Inhomogeneity of coronary remodeling within the same artery — an intravascular ultrasound study
Authors: T Nishioka, N. Hakamata, A. Uehata, S. Katsushika, B. Takaso, K. Isojima, T. Nagal, H. Luo, R.J. Siegel
Journal: Journal of the American College of Cardiology (1998)
Nikolsky's sign: is it‘dry’ or is it ‘wet’?
Authors: T.G. SALOPEK
Journal: British Journal of Dermatology (1997)

Nikolsky's signs refers to the ability to induce peripheral extension of a blister as a consequence of applying lateral pressure to the border of an intact blister. Although initially used in reference to the pemphigus group of blistering dermatoses, a positive Nikolsky's sign can be seen in other bullous diseases such as toxic epidermal necrolysis and staphylococcus scalded skin syndrome. Appreciating whether the blister is 'wet' or 'dry' at the site of a positive Nikolsky's signs may have both diagnostic and prognostic significance which I illustrate with several clinical cases. Lastly, I review the significance of a positive Nikolsky's sign.
Homologous Recombination Is the Principal Pathway for the Repair of DNA Damage Induced by Tirapazamine in Mammalian Cells
Authors: James W. Evans, Sophia B. Chernikova, Lisa A. Kachnic, Judit P. Banath, Olivier Sordet, Yvette M. Delahoussaye, Alejandro Treszezamsky, Brian H. Chon, Zhihui Feng, Yongchuan Gu, William R. Wilson, Yves Pommier, Peggy L. Olive, Simon N. Powell, J. Martin Brown
Journal: Cancer Research (2008)

Abstract Tirapazamine (3-amino-1,2,4-benzotriazine-1,4-dioxide) is a promising hypoxia-selective cytotoxin that has shown significant activity in advanced clinical trials in combination with radiotherapy and cisplatin. The current study aimed to advance our understanding of tirapazamine-induced lesions and the pathways involved in their repair. We show that homologous recombination plays a critical role in repair of tirapazamine-induced damage because cells defective in homologous recombination proteins XRCC2, XRCC3, Rad51D, BRCA1, or BRCA2 are particularly sensitive to tirapazamine. Consistent with the involvement of homologous recombination repair, we observed extensive sister chromatid exchanges after treatment with tirapazamine. We also show that the nonhomologous end-joining pathway, which predominantly deals with frank double-strand breaks (DSB), is not involved in the repair of tirapazamine-induced DSBs. In addition, we show that tirapazamine preferentially kills mutants both with defects in XPF/ERCC1 (but not in other nucleotide excision repair factors) and with defects in base excision repair. Tirapazamine also induces DNA-protein cross-links, which include stable DNA-topoisomerase I cleavable complexes. We further show that γH2AX, an indicator of DNA DSBs, is induced preferentially in cells in the S phase of the cell cycle. These observations lead us to an overall model of tirapazamine damage in which DNA single-strand breaks, base damage, and DNA-protein cross-links (including topoisomerase I and II cleavable complexes) produce stalling and collapse of replication forks, the resolution of which results in DSB intermediates, requiring homologous recombination and XPF/ERCC1 for their repair. [Cancer Res 2008;68(1):257–65]
Benign Struma Ovarii in a Patient With Invasive Papillary Thyroid Cancer: Detection with I-131 SPECT-CT
Authors: William Macdonald, Jonathan Armstrong
Journal: Clinical Nuclear Medicine (2007)

A 78-year-old woman was referred for I-131 therapy following total thyroidectomy for invasive papillary thyroid cancer. The thyroglobulin titer was markedly elevated following thyroxine withdrawal, and she was given 5,550 MBq (150 mCi) of I-131 following additional pretreatment with rTSH (Thyrogen). A posttherapy scan showed intense, focal activity in the pelvis, which localized to the right ovary on SPECT-CT fusion examination. Contrast CT confirmed a cystic right ovarian tumor and she underwent laparoscopic oophorectomy, which revealed a benign follicular thyroid adenoma (struma ovarii). At 6-month follow-up, a whole body iodine scan was normal, and the TSH-stimulated thyroglobulin was undetectable.
Utility of B-Type Natriuretic Peptide as a Screen for Left Ventricular Dysfunction in Patients With Diabetes
Authors: Danny Liew, Hans Schneider, Joe D’Agostino, Jonathan Shaw, Henry Krum
Journal: Diabetes Care (2004)

In their study recently published in Diabetes Care , Epshteyn et al. (1) found that plasma B-type natriuretic peptide (BNP) was able to discriminate between diabetic patients with and without left ventricular (LV) dysfunction, even among the subset without any clinical suspicion of heart failure. It is this last observation that supports the use of BNP as a screen for LV dysfunction among people with diabetes. Detection of LV dysfunction, an early feature of diabetic heart disease, presents an important opportunity for prevention of …
Top molecular geneticist resigns London post
Authors: F Goodlee
Journal: BMJ (1994)

The head of Britain's leading gene therapy centre has resigned because of government cutbacks. Professor Kay Davies, director of the Medical Research Council's Clinical Sciences Centre in London, said that government disruption of hospital services in London had impeded her research programme, forcing her to take on time consuming administrative duties and making it difficult to recruit research staff.

The Clinical Sciences Centre was set up in 1991 at a cost of pounds …
Sporadic Cases of Hereditary Systemic Amyloidosis
Authors: Maria João Mascarenhas Saraiva
Journal: New England Journal of Medicine (2002)

The systemic amyloidoses comprise a spectrum of acquired and hereditary diseases caused by the deposition of characteristic fibrillar material in various organs and tissues throughout the body. These fibrils are 7 to 10 nm wide, rigid, and nonbranching, and they have in common a twisted β-pleated sheet structure. They also have unique tinctorial properties, including apple-green birefringence when viewed under polarized light after staining with Congo red. Several apparently unrelated proteins can form amyloid fibrils and cause specific clinical forms of amyloidosis.There are two major forms of acquired systemic amyloidosis. The first, systemic amyloid A (AA) amyloidosis, is associated . . .
Long term follow up of women with borderline cervical smear test results: effects of age and viral infection on progression to high grade dyskaryosis.
Authors: L. Hirschowitz, A. E. Raffle, E. F. Mackenzie, A. O. Hughes
Journal: BMJ (1992)

OBJECTIVE--To follow up and assess the significance of borderline change in cervical smears. DESIGN--Retrospective study of women undergoing routine cervical cytological screening in 1981. SETTING--Avon Cervical Screening Programme, covering 250,000 women in Bristol and Weston super Mare. SUBJECTS--437 women showing borderline cervical changes in 1981 and 437 age matched controls with normal results in 1981. MAIN OUTCOME MEASURES--Cytological progression to high grade dyskaryosis (cervical intraepithelial neoplasia grade III or invasive carcinoma). RESULTS--During follow up ranging from 13 to 106 months 98 of the 437 women (22.4%) with borderline cytological changes on routine cervical cytology screening had a subsequent smear test showing high grade dyskaryosis compared with three of the 437 women (0.9%) in the control group. The risk of progression was greater in women aged 20 to 39 than in those aged 40 and over. Human papillomavirus infection had initially been diagnosed cytologically in 101 of the 437 (23%) women with borderline results. Significantly fewer of these women developed high grade dyskaryosis (13/98 (13%) v 88/339 (26%), p less than 0.05). CONCLUSIONS--Women with borderline smear test results are at increased risk of developing high grade dyskaryosis, particularly if the borderline changes occur without cytological features of human papillomavirus infection. Progression occurs within three years in 50% of cases, although a linearly increasing risk was sustained over the nine years of follow up and was greatest in women aged 20 to 39. Careful follow up of these women is indicated.
Use of an Expandable Ultraflex Stent in the Treatment of Malignant Rectal Stricture
Authors: I. Raijman, M. Siemens, N. Marcon
Journal: Endoscopy (1995)

Obstructive colorectal cancer is usually an indication for surgical intervention. For patients with metastatic disease, medical contraindications, or those who refuse surgery, palliation by nonoperative means is necessary. The advent of expandable metallic stents may allow for speedy palliation. We have treated one patient with unresectable colon cancer with a new selfexpanding endoprosthesis made of nitinol (Ultraflex, Microvasive, Watertown, MA, U.S.A.).
Politicians and scientists
Authors: H Keen
Journal: BMJ (1990)

Early B cell development depends upon the surface expression of Ig heavy chain protein (mu) in a signaling complex known as the pre-B cell receptor (pre-BCR). In addition to mu, the pre-BCR consists of the surrogate light chains VpreB and lambda5 and the transmembrane signal transduction proteins Ig-alpha and Ig-beta. Expression of this complex is associated with changes in surface marker expression, gene transcription, and Ig gene rearrangement. Mutations preventing the expression of either mu or lambda5 result in developmental arrest, but the precise roles of the various components of the pre-BCR remain unclear. Using mice transgenic for a surface-expressed, but truncated, form of mu that cannot associate with surrogate light chains, we have studied the role of surrogate light chains in B cell development. We found that expression of the truncated mu transgene resulted in changes in surface marker expression, germline kappa locus transcription, and V(D)J recombinase targeting indistinguishable from those induced by intact mu protein. These experiments lead us to conclude that surrogate light chains, while necessary for the assembly of the wild-type pre-BCR, are not directly involved in pre-BCR signaling or otherwise required for early B cell development.
Eradication of polio threatened by $300m funding shortfall
Authors: A. Vass
Journal: BMJ (2002)

A funding gap of $275m (£191m; €313m) threatens the final push towards the global eradication of poliomyelitis, a coalition of international organisations and charities has claimed.

Under the global polio eradication initiative, numbers of cases of polio continue to fall and are now at an all time low. Last year there were just 537 new cases, down from 2979 in 2000. The number of countries where polio is endemic also fell from 20 in 2000 to 10 last year.

The opportunity to finally stamp out the disease, however, is under threat, owing …
The Natural History and Predictors of Outcome Following Biochemical Relapse in the Dose Escalation Era for Prostate Cancer Patients Undergoing Definitive External Beam Radiotherapy
Authors: Zachary S. Zumsteg, Daniel E. Spratt, Paul B. Romesser, Xin Pei, Zhigang Zhang, William Polkinghorn, Sean McBride, Marisa Kollmeier, Yoshiya Yamada, Michael J. Zelefsky
Journal: European Urology (2014)
The Tumor Lysis Syndrome-Reply
Authors: Nicholas J. Vogelzang
Journal: JAMA (1983)

<h3>In Reply.—</h3> Dr Baumann and co-workers are to be commended for reporting a second case of tumor lysis syndrome in a patient with small-cell lung carcinoma. Their patient was similar to ours, with acute rises in the serum phosphorus, potassium, creatinine, uric acid, and LDH levels, but, fortunately, had a reversible form of the syndrome. Dr Baumann and colleagues comment on the low incidence of the syndrome (one in 300 patients), but our incidence was one in 86 patients at the University of Minnesota. Among those 86 patients, several died within days of initiating chemotherapy and were presumed to have died of tumor progression. However, they were not adequately examined for the tumor lysis syndrome. Also, etoposide (Veposide) has recently been approved for marketing and is used in refractory small-cell carcinoma, and its high level of activity as a single agent<sup>1</sup>may increase the frequency of this syndrome. Allopurinol