tbuckley/cabot-search huggingface dataset:
Abstract 2675: CXCL12 (SDF-1) and its truncation products in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) receiving ON 01910.Na (Rigosertib) in phase I trials
Authors: Sool Y. Cho, Shyamala C. Navada, Lewis R. Silverman, James F. Holland, John Roboz
Journal: Cancer Research (2012)

Abstract CXCL12 (stromal cell-derived factor, SDF-1), is an 8 kDa peptide chemokine. The interaction between CXCL12 and its receptor, CXCR4, plays a pivotal role in the trafficking of hematopoietic stem cells between bone marrow and peripheral blood. The CXCL12/CXCR4 axis may play a role in the pathogenesis of myeloid neoplasms. We developed a technique for the determination of intact (full length) CXCL12 and its protease(s)-induced truncation products in plasma from patients with myeloproliferative neoplasms (Cancer Res., 70, 3402, 2010). In the present work, we are extending our observations to the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). CXCL12 concentrations in normal subjects were 16.6 ± 9.4 ng/mL (n=10). In primary myelofibrosis (PMF), the concentrations were 5.8 ± 4.0 ng/mL (n=15), and in polycythemia vera (PV) 7.9 ± 3.6 ng/mL (n=21). Now we report that in MDS/AML, the concentrations are 2.2 ± 2.1 ng/mL (n=8). In normal subjects, truncation products, due to proteolysis, were not detectable (≥ 1.0 ng/mL). The loss of 2, 3, 4, and 5 amino acids (aa) from CXCL12 were confirmed by molecular masses measured using electrospray ionization mass spectrometry. Quantification was completed with synthetic standards. In MDS/AML patients the concentration of the truncation product corresponding to −2 aa (KP removed),-3 aa (KPV removed), −4 aa (KPVS removed) and −5 aa (KPVSL removed) were 2.7 ± 3.2 ng/mL, 2.4 ± 2.1 ng/mL, 3.8 ± 3.0 ng/mL, and 2.5 ± 2.4 ng/mL, respectively. The total concentration of all truncation products was 11.3 ± 5.8 ng/mL. For comparison, the concentration of total truncation products was 28.7 ± 19.9 for PMF, and 31.1 ± 7.8 for PV. Patients with these myeloid malignancies have lower CXCL12 concentrations compared to normal controls and high concentrations of proteolytic truncation products which are absent in normal plasma. Of the 8 patients with MDS (n=3) and AML (n=5), treated with continuous infusion of ON 01910.Na (rigosertib), 650 - 1,700 mg/m2, in a Phase I dose escalation study, 4 patients attained a partial or complete bone marrow remission according to International Working Group criteria. The concentration of intact CXCL12 rose at 72 h in responding patients, whereas those who failed to respond had a decrease. These data suggest that monitoring intact CXCL12 and its truncation products may provide a marker of response to treatment with ON 01910.Na, as well as insight into the role of the CXCL12/CXCR4 axis in the pathobiology of these bone marrow diseases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2675. doi:1538-7445.AM2012-2675
1046-174 The pivotal link between hepatitis C virus infection and increased arterial stiffness in patients with end stage renal failure
Authors: Nobuyuki Oyake, Toshio Shimada, Yo Murakami, Yutaka Ishibashi, Harumi Katoh, Shinichi Inoue, Yoko Ohta
Journal: Journal of the American College of Cardiology (2004)
Criterion-Related Validity of Diagnostic Criteria for Alexithymia in a General Hospital Psychiatric Setting
Authors: Isao Fukunishi, Takashi Hosaka, Takayuki Aoki, Takaharu Azekawa, Arimitsu Ota, Hitoshi Miyaoka
Journal: Psychotherapy and Psychosomatics (1996)

The diagnostic criteria for alexithymia (DCA) was proposed by Fava et al. in 1995. The purpose of this study was to examine the criterion-related validity of the DCA in a general hospital psychiatric setting.The subjects included 126 outpatients with psychiatric disturbance. The severity of alexithymic characteristics was assessed using the DCA and Beth Israel Hospital Psychosomatic Questionnaire (BIQ). Two Japanese versions of the 26-item Toronto Alexithymia Scale (TAS-26) and Minnesota Multiphasic. Personality Inventory-2 (MMPI-2) were administered.The DCA had relatively high sensitivity and specificity, indicating adequate discriminant validity. The discriminant validity of the DCA was also supported by significant associations of the DCA with the TAS-26 and MMPI-2. These results indicate that when used for screening, the DCA has adequate criterion-related validity.The DCA may be clinically useful in a general hospital psychiatric setting.
Effects of erythropoietin on left ventricular hypertrophy in adults with severe chronic renal failure and hemoglobin &lt;10 g/dL
Authors: Juan Carlos Ayus, Alan S. Go, Fernando Valderrabano, Eduardo Verde, Soledad Garcia de Vinuesa, Steven G. Achinger, Victor Lorenzo, Allen I. Arieff, Jose Luao
Journal: Kidney International (2005)
Seroepidemiology of hepatitis C virus infection in Taiwan
Authors: Shou-Dong Lee, Cho-Yu Chan, Yan-Jenn Wang, Jaw-Ching Wu, Kwok-Hung Lai, Yang-Te Tsai, Kwang-Juei Lo
Journal: Hepatology (1991)

The prevalence of antibody to hepatitis C virus among Chinese subjects in Taiwan was evaluated using a commercially available enzyme immunoassay. The overall prevalence of antibody to hepatitis C virus was 0.28% among 1,419 healthy subjects, 0.8% among 500 unselected paid blood donors and 0.4% among 793 pregnant women. The three offspring of the mothers positive for antibody to hepatitis C virus were all found to be positive for antibody to hepatitis C virus at birth but all became negative by the age of 6 mo. Among healthy subjects, none of 1,000 school children and young adolescents had antibody to hepatitis C virus. Among patients in selected "high-risk" groups, antibody to hepatitis C virus was detected in 100% of 9 hemophiliac patients who were positive for antibody to human immunodeficiency virus, in 53% of 115 intravenous drug abusers, in 34.4% of 96 hemodialysis patient and in 15.8% of 19 homosexual men who were positive for antibody to human immunodeficiency virus. Only 7.1% of 196 prostitutes, 5.9% of 34 spouses of patients positive for antibody to hepatitis C virus and 0.5% of 201 brothelgoers had antibody to hepatitis C virus. These findings suggest that hepatitis C virus is transmitted mainly by the parenteral route in Taiwan. Transmission from mother to infant is not an important mode of spread of hepatitis C virus.
Application of airline pilots' hours to junior doctors.
Authors: A. M. Wilson, G. Weston
Journal: BMJ (1989)

To determine the staff required if the rules for airline pilots' hours of work are applied to junior doctors.Junior anaesthetists recorded their workload from 1 March 1988 to May 31 1988.District general hospital.Two groups of three junior anaesthetists sharing a one in three rota to provide continuous emergency cover.By using the guidelines published by the Civil Aviation Authority in The Avoidance of Excessive Fatigue in Aircrews schedules were drawn up to cover the hours that junior doctors had been on duty.Each anaesthetist provided emergency and routine cover for 48-112 (mean 75) hours each week. To cover the work of six junior anaesthetists on an annual basis would require 26 doctors if they were working within the Civil Aviation Authority's guidelines.Junior anaesthetists' hours are much longer than those of airline pilots. Both professions entail considerable periods of monitoring interspersed with episodes of high demands on physical and cognitive skills. Errors induced by fatigue made by anaesthetists and pilots could result in death. The medical profession should define rules similar to those of the aviation authority to prevent junior doctors having to work unsafe numbers of hours.
Abstract 2435: Validation of Cynomolgus monkeys as relevant species for safety assessment of a novel human BiTE antibody platform for cancer therapy
Authors: Benno Rattel, Roman Kischel, Oliver Thomas, Matthias Friedrich, Doris Rau, Evelyn Ebert, Tobias Raum, Andreas Wolf, Susanne Mangold, Majk Kvesic, Patrick A. Baeuerle, Peter Kufer
Journal: Cancer Research (2010)

Abstract Nonclinical safety assessment of biopharmaceuticals for human use relies on their cross-reactivity with the respective target in other species, the absence of which precludes testing in commonly used animal models. This is the case for a first-generation of T cell-engaging BiTE antibodies, which solely cross-react with T cells of chimpanzee. BiTE antibodies are designed to transiently connect the CD3 subunit of T cell receptors on T cells with an antigen on target cells. This can very effectively activate T cells, leading to a potent redirected lysis of target cells. Here, we have generated a series of novel human anti-CD3 antibodies that cross-react with non-human primate species, including Cynomolgus monkeys (Macaca fascicularis) and marmoset (Callithrix jacchus). The variable domains of a selected anti-CD3 antibody were used to generate next-generation BiTE antibodies specific for (1) CD33, a target antigen for treatment of acute myelogenous leukemia, (2) melanoma-associated chondroitin sulfate proteoglycan (MCSP), a potential target for treatment of melanoma, and (3) epidermal growth factor receptor 1 (EGFR), a validated target for treatment of colorectal cancer. In vitro, CD33-, MCSP- and EGFR-specific BiTE antibodies showed comparable binding to CD3 on human and macaque T cells, and to CHO cells expressing CD33, MCSP and EGFR of human or macaque origin. In human and macaque cell-based assays, bispecific binding triggered redirected target cell lysis as well as conditional T cell activation, as previously described for first-generation BiTE antibodies. When continuously infused for one week to Cynomolgus monkeys, the CD33-specific BiTE antibody caused depletion of CD33-expressing peripheral blood cells at tolerated doses, and reached a maximum tolerated dose (MTD) at 120 µg/m2/day. The EGFR-specific BiTE antibody reached an MTD at 150 µg/m2/kg. In contrast, the MCSP-specific BiTE antibody was well-tolerated up to a dose of 5,000 µg/m2/day. Our primate data suggest that the tolerability and toxicity of CD33-, MCSP- and EGFR-specific BiTE antibodies were apparently determined by target cell-dependent bispecific binding, and not by monovalent binding to CD3 on macaque T cells. Our data validate the Cynomolgus monkey as a relevant species for assessing the safety and tolerability of next-generation BiTE antibodies that use a more broadly cross-reactive anti-CD3 human single-chain antibody. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2435.
Oral 14, Spontaneous atrophic scarring of the cheeks: atrophia maculosa varioliformis cutis?
Authors: R.F. Rose, G. Taylor *, V. Goulden, S.M. Clark
Journal: British Journal of Dermatology (2007)

A 3-year-old girl presented with a 2-year history of an asymptomatic facial eruption. She developed spontaneous erythematous papules which healed with scarring. Lesions occurred throughout the year with no obvious link to ultraviolet exposure. The child was otherwise fit and well. Family history was unremarkable; she is the only child of parents who are distant cousins. On examination, her skin was well hydrated with no eczematous change, no typical acneiform features and no evidence of keratosis pilaris. Atrophic varicella-like scarring was evident on both cheeks which did not herniate on palpation. Antinuclear antibody and porphyrin screens were negative and limited monochromator phototesting and photoprovocation testing was normal. Differential diagnoses included scarring secondary to varicella, atrophoderma vermiculatum, hydroa vacciniforme and infantile acne but these were excluded by the chronic course, clinical findings and lack of seasonal variation. Atrophia maculosa varioliformis cutis is a rare condition with approximately 20 reports in the literature.1,2 It was first described by Heidingsfeld in 1918. Typically, spontaneous macular atrophy is reported on the face in the absence of preceding trauma or inflammation but lesions have been described elsewhere on the body. The lesions may be linear, punctate or rounded and some reports do describe initial erythema and scale. The course is usually chronic but slowly progressive. Histological findings are variable and include epidermal thinning, a mild perivascular lymphocytic infiltrate, fragmented elastic fibres and normal or increased collagen. Pathogenesis is unknown and most cases are sporadic, although familial occurrence has been reported. References 1 Paradisi M, Angelo C, Conti G et al. Atrophia maculosa varioliformis cutis: a pediatric case. Pediatr Dermatol 2001; 18:478–80. 2 Dall’Oglio F, Nasca M, Taparelli F et al. Familial atrophia maculosa varioliformis cutis: an ultrastructural study. Pediatr Dermatol 2001; 18:230–3.
PARENTAL KNOWLEDGE REGARDING LIFE-LONG CONGENITAL CARDIAC CARE
Authors: Susan M. Fernandes, Amy Verstappen, Kathy Ackerman, Elizabeth E. Adams, Cheryl Barton, Petar Breitinger, Stephen Crumb, Kirsten Dummer, Paul Khairy, Michael J. Landzberg, Rachel Linstead Goldsmith, JoAnn Nieves, Arwa Saidi, Masato Takahashi, Sonja Ziniel, Roberta Williams
Journal: Journal of the American College of Cardiology (2010)
TENDON ADVANCEMENT AND TENDON RETROPLACEMENT.
Authors: CHARLES HERMON THOMAS
Journal: JAMA (1895)

Reference is here made to advancement of tendons as distinguished from tendon resection or tendon shortening. In the latter two, the stump of the partially severed tendon furnishes the point of attachment of the portion to be brought forward. Not so, however, in tendon advancement. This operation is required as a remedy for strabismus, insufficiencies, and for the results of old operations excessive in their effects. Tendon retroplacement is here recommended as a control procedure, in connection with complete tenotomy, and is to be practiced at the time and as a part of the original operation. It may as well be said at once that in the opinion of the writer, the operation for tendon advancement, as described by Stevens and performed with the singularly delicate instruments which he has given us, may be substituted with advantage for all other operations heretofore described. The small conjunctival opening with its minimum
Specific nuclear envelope transmembrane proteins can promote the location of chromosomes to and from the nuclear periphery
Authors: Nikolaj Zuleger, Shelagh Boyle, David A Kelly, Jose I de las Heras, Vassiliki Lazou, Nadia Korfali, Dzmitry G Batrakou, K Natalie Randles, Glenn E Morris, David J Harrison, Wendy A Bickmore, Eric C Schirmer
Journal: Genome biology (2013)

Different cell types have distinctive patterns of chromosome positioning in the nucleus. Although ectopic affinity-tethering of specific loci can be used to relocate chromosomes to the nuclear periphery, endogenous nuclear envelope proteins that control such a mechanism in mammalian cells have yet to be widely identified. To search for such proteins, 23 nuclear envelope transmembrane proteins were screened for their ability to promote peripheral localization of human chromosomes in HT1080 fibroblasts. Five of these proteins had strong effects on chromosome 5, but individual proteins affected different subsets of chromosomes. The repositioning effects were reversible and the proteins with effects all exhibited highly tissue-restricted patterns of expression. Depletion of two nuclear envelope transmembrane proteins that were preferentially expressed in liver each reduced the normal peripheral positioning of chromosome 5 in liver cells. The discovery of nuclear envelope transmembrane proteins that can modulate chromosome position and have restricted patterns of expression may enable dissection of the functional relevance of tissue-specific patterns of radial chromosome positioning.
Anaphylaxis induced by horsefly bites: Identification of a 69 kd IgE-binding salivary gland protein from Chrysops spp. (Diptera Tabanidae) by western blot analysis
Authors: Wolfgang Hemmer, Margarete Focke, Dieter Vieluf, Barbara Berg-Drewniok, Manfred Götz, Reinhart Jarisch
Journal: Journal of Allergy and Clinical Immunology (1998)
Obsolescence Before Use— A Modern Parable
Authors: Michael Weintraub
Journal: JAMA (1976)

<h3>To the Editor.—</h3> Some critics of excessive participation of the "poor" in medical experiments have suggested prohibition of their use in such studies ("poor" defined as prisoners, students, and patients attending the clinics of teaching hospitals—in short, populations "deprived not only for strictly economic reasons, but also because of social, cultural, administrative, and political factors"). In their place, others not disadvantaged or dependent would participate. To ensure equality of opportunity, computer techniques would be used to select potential volunteers for studies. Other prohibited groups would be those thought by some to be unable to offer true informed consent, eg, children, the aged, soldiers. As I dozed over the discussion of these issues, an insight into the future unfolded before me: Employment Manager: Good Morning, what can I do for you? Applicant: I'd like to apply for the job you advertised in the paper. Employment Manager: Very well, may I have
Human Prolactin Receptor Variants in Breast Cancer
Authors: Jianping Meng, Chon-Hwa Tsai-Morris, Maria L. Dufau
Journal: Cancer Research (2004)

Prolactin plays an essential role in the development of rodent mammary tumors and is a potent mitogen in human normal and cancerous breast tissues/cells. In this study, we have analyzed the expression of prolactin receptors, including the long receptor form (LF; stimulatory) and two novel short forms (SFs; S1a and S1b) derived from alternative splicing that are inhibitory of the activation induced by prolactin through the LF. Southern analysis of breast cancer profiling arrays revealed that 29 patients (group I) expressed an elevated LF, 10 patients (group II) showed decreased LF, and 8 patients (group III) had no change relative to the adjacent normal tissue. Their respective SF expression was increased in 21 patients of group I and generally decreased in groups II and III. However, the ratio of SF to LF was significantly decreased in 76% of the breast tumors and distributed evenly among the groups. Quantification of differential expression of prolactin receptor variants by real-time PCR in 15 pairs of human normal and tumor breast-matched tissues revealed a similar significant decrease in the ratio of SF to LF in the tumor tissue. Consistent lower ratio of SFs to LFs was confirmed in 8 of ten different breast cancer cell lines compared with normal mammary Hs578Bst and MCF10A cells. Because SFs act as dominant negative regulators of the stimulatory actions of the LF in vitro, their relatively reduced expression in cancer could cause gradations of unopposed prolactin-mediated LF stimulatory function and contribute to breast tumor development/progression.
Obese Non-diabetic Patients
Authors: J. M. Stowers, P. D. Bewsher
Journal: BMJ (1970)

thought to be Haemophilus influenzae, or possi- bly a coliform, it grew well on nutrient agar in t-he absence of X and V factors, and did not grow on McConkey's agar.It was finally proved to be Pasteurella multocida, a mouse dying 24 hours after inoculation with a culture of the organism.This organism was sensitive in vitro to penicillin, chloramphenicol, tetracyciine, erythromycin, and cephaloridine.The white blood cell count was only 9,000/cu.mm. on admission, 85 % of these cells being neutrophils.Discharge from the right ear produced a growth of Staphylococcus aureus, but no other organism was identified.The patient was treated initially with full dioses of penicillin, chloramphenicol, and sul- phadimidine.Chloramphenicol was discontinued after one week, and the dose of sulphadimidine was reduced.After a further week the penicillin was replaced by a short oral course of cloxacillin, since the staphylococcus grown from the middle ear was penicillin-resistant.A second C.S.F.specimen obtained 10 days after the first was sterile, but still contained 22 leucocytes (mainly lymphocytes) per cu.mm.Satisfactory progress was maintained, and the patient was discharged home after one month in hospital.No contact with dogs or cats was admitted on direct questioning, and no symptoms of bron- chitis had been noticed.
Diagnosis of Subdural Hematoma
Authors: Arthur E. Lyons
Journal: JAMA (1972)

<h3>To the Editor.—</h3> The question of diagnosis of chronic subdural hematomas (220:1370,1972) was well answered by Drs. McLaurin and Shapiro, but I believe warrants further amplification. Progressive signs of intracranial deterioration should always prompt the carrying out of definitive diagnostic procedures that are available. Needless to say, these should be carried out as soon as possible in order to rule out a surgically remediable lesion. Consideration must be given to the safety of such diagnostic tests and the potential morbidity. A chronic subdural hematoma exerts its effect by slowly expanding, causing compression of adjacent brain and later, more remote areas are involved, as enlargement proceeds. Symptoms are related to the speed of the expansion and the ability of the brain to compensate. In this respect, the subdural hematoma acts as a noninvasive neoplasm and must be considered in a similar light. In my opinion, lumbar puncture, besides being notoriously misleading,
Solitary functioning kidney and diverse genital tract malformations associated with hepatocyte nuclear factor-1β mutations
Authors: Coralie Bingham, Sian Ellard, Trevor R.P. Cole, Katrin E. Jones, Lisa I.S. Allen, Judith A. Goodship, Timothy H.J. Goodship, Daniela Bakalinova-Pugh, Gavin I. Russell, Adrian S. Woolf, Anthony J. Nicholls, Andrew T. Hattersley
Journal: Kidney International (2002)
Sidney Cohen, MD
Authors: L. J. West
Journal: JAMA (1988)

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