tbuckley/cabot-search huggingface dataset:
421. Liver Contains Sufficient Sulfatase Modifying Factor for 4-Sulfatase and Correction of MPS VI with Neonatal Retroviral Gene Therapy in Cats
Authors: Mark Haskins, Thomas O'Malley, Bin Wang, Jason Metgcalf, Ping Wang, John Hopwood, Katherine P. Ponder
Journal: Molecular Therapy (2005)

Sulfatases are enzymes that remove a sulfate from a substrate. 4-sulfatase (4S; also known as arylsulfatase B) is a lysosomal enzyme that removes a sulfate from the 4 position of N-acetylgalactosamine, a component of the glycosomaminoglycan (GAG) dermatan sulfate. Deficient activity of 4S results in mucopolysaccharidosis VI (MPS VI), a disorder that includes bone and joint abnormalities, corneal clouding, and cardiac disease, but does not usually involve the brain. The lack of neurological involvement makes this an excellent candidate for somatic therapies. All sulfatases are modified post-translationally by enzymes designated as sulfatase modifying factors (SUMF) that convert a cysteine in the active site to a C-alpha-formylglycine, which is absolutely essential for enzyme activity. SUMF is readily saturated after over expression of a sulfatase in fibroblasts in vitro, resulting in limitations in the amount of enzyme that can be produced and a reduction in activity of other sulfatases that require the same modification. It was, therefore, unclear if hepatocytes would contain sufficient SUMF activity to modify the 4S produced by hepatocytes after liver-directed gene therapy for MPS VI. A retroviral vector (RV) designated hAAT-f4S-WPRE expressing feline 4S was generated. 4S-deficient feline fibroblasts were transduced in vitro with increasing multiplicities of infection. The 4S enzyme activity (4MU-sulfate assay) and 4S protein levels (immunoblot) were directly proportional to the DNA copy number, which leveled off at about 2 copies per cell despite using higher multiplicities of infection. This likely reflects an inhibition of transduction when large amounts of vector are used, which has been described previously, suggesting that SUMF is not limiting when relatively low copy numbers are achieved. hAAT-f4S-WPRE (4.2-3.4X10E9 TU/kg) was injected IV into 6 newborn cats with MPS VI. They achieved stable expression at 109+/-49 U/ml in serum, which is 10-fold normal and has been maintained for up to 1.5 years in the oldest animals. Analysis of liver biopsies demonstrated that the 4S enzyme activity was directly proportional to the amount of 4S protein, suggesting that all of the enzyme was functional, and that modification by SUMF was not limiting. The cats have marked improvement in the clinical skeletal manifestations. The cats also have biochemical evidence of improvement, which includes high levels of 4S and a reduction in GAG and secondary lysosomal enzyme activity in other organs. We conclude that liver contains sufficient SUMF to modify 4S, and that liver-directed gene therapy can markedly improve the clinical manifestations of this disorder.
UK research community is to consult on use of animals containing human material
Authors: S. Mayor
Journal: BMJ (2009)

UK researchers have launched a wide ranging consultation on the scientific, ethical, safety, and regulatory issues associated with the use in scientific studies of animals that contain human material. They aim to develop a robust and regulatory framework.

Research involving the use of animal material in humans is already tightly regulated. But although there have been major research developments involving the incorporation of human material into animals over the past 40 years, currently no clear regulation exists in this area, and little public discussion has taken place of what is considered acceptable.

Martin Bobrow, chairman of the working group that will coordinate the consultation and emeritus professor of medical genetics at Cambridge University, said, “Consultation for the Human Fertilisation and Embryology Act last year enabled widespread discussion about research on human embryos, including those incorporating animal genetic material. But research involving animals containing human …
In evolutionary games, enlightened self-interests are still ultimately self-interests
Authors: Thomas Getty
Journal: Behavioral and Brain Sciences (2007)

Evolutionary theory provides a firm foundation for the unification of the behavioral sciences, and the beliefs, preferences, and constraints (BPC) model is a useful analytical tool for understanding human behavior. However, evolutionary theory suggests that if other-regarding preferences expressed by humans have evolved under selection, they are ultimately, if not purely, in the constrained, relative self-interests of individuals who express them.
Washington Presence First Step In ASCO's Strategic Plan
Authors: C. Vanchieri, C. Thomsen
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Washington Presence First Step In ASCO's Strategic Plan Get access Cori Vanchieri, Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar Chris Thomsen Chris Thomsen Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 5, 7 March 1990, Pages 343–344, https://doi.org/10.1093/jnci/82.5.343 Published: 07 March 1990
HIV-related tuberculosis in a transgender network - Baltimore, Maryland, and New York City area, 1998-2000.
Authors: T. R. Sterling, R. L. Stanley, D. Thompson, G. A. Brubach, A. Madison, S. Harrington, W. R. Bishai, R. E. Chaisson, J. Betz-Thomas, S. Bur, N. Baruch, G. C. Benjamin, C. R. Driver, B. Kreiswirth
Journal: MMWR Morbidity and Mortality Weekly Report (2000)
Abstract 1216: Effects of phenformin in LKB1/KRAS mutated non-small cell lung cancer patient derived xenograft
Authors: Massimo Moro, Luca Roz, Roberto Caserini, Ugo Pastorino, Gabriella Sozzi
Journal: Cancer Research (2014)

Abstract Metformin is an oral antidiabetic drug of the biguanide class. Several epidemiological and case-control studies reported that diabetics using metformin may have lower cancer risk in comparison to those using other antidiabetic medications. Recent studies in experimental models suggest that another biguanide, phenformin, has higher anticancer activity compared with metformin. The aim of this study was to evaluate the effects of metformin and phenformin in Non-Small Cell Lung Cancer (NSCLC) models. In particular, the effects of these compounds in LKB1 or LKB1/KRAS mutated compared to wild type models have been investigated. NSCLC cell lines (A549, H460, H1299, LT73) have been treated with either metformin or phenformin to evaluate in vitro dose/response depending on the different mutational status of KRAS and LKB1 genes. The effects of the two biguanide have been investigated also in vivo models, exploiting the panel of Patient Derived Xenografts (PDXs) directly generated from NSCLC patients in our Institute. In vitro experiments indicated that cell lines with already impaired metabolism (LKB1 and/or KRAS mutated) were more sensitive to phenformin treatment. Interestingly, treatments of these cell lines with r phenformin resulted in a 50% decrease in the amount of CD133+ Tumor Initiating Cells (TIC). Moreover, high doses of phenformin (LD75) did not result in the increase of TIC previously observed after Cisplatin treatment. In vivo, early treatments (Tumor Volume = 50-100mm3) of an LKB1 mutated PDX model resulted in a significant reduction of tumor volume (300 ± 50 mm3 in phenformin treated vs 750 ± 100 mm3 in vehicle treated tumors) already after three weeks of treatment (100mg/Kg/day). Importantly, no regrowth was observed in responding tumors even after the end of treatments. No effects were observed in LKB1 wild type PDX treated with phenformin. Taken together, these preliminary data indicate a selective action of phenformin on LKB1 mutated lung adenocarcinoma models in vitro and in vivo. Interestingly, this compound seems to be more active in TIC than normal chemotherapeutic drugs (i.e. cisplatin). Effects of biguanide on TIC could be the cause of the lack of tumor regrowth after treatment, thus making these compounds potentially useful in counteracting disease recurrence and/or metastasis formation. Further investigations are needed to elucidate the different effects of metformin and phenformin in double mutated (LKB1 and KRAS) PDXs models. Citation Format: Massimo Moro, Luca Roz, Roberto Caserini, Ugo Pastorino, Gabriella Sozzi. Effects of phenformin in LKB1/KRAS mutated non-small cell lung cancer patient derived xenograft. [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 1216. doi:10.1158/1538-7445.AM2014-1216
Personality Traits in Patients with Acute Low-Back Pain
Authors: Tatjana M. Sivik
Journal: Psychotherapy and Psychosomatics (1991)

This study investigates the possibilities to identify, within a group of acute low-back pain patients, individuals with psychogenic etiology to pain. 26 acute back pain patients and 25 healthy control sujects were tested with the Minnesota Multiphasic Personality Inventory Hysteria: (Hs), Hypochondria (Hy), Depression (D); Cesarek-Marke Personality Scale: Aggression (Agg), Defence of status (Dst), Guilt (Gui); Mood Adjective Check List: (Hedonism, Activity, Calmness = Hed, Act, Clm) and a 'pain questionnaire' including 'pain drawing'. Differences between groups and correlation patterns between test variables indicate that a combination of Hs, Hy, D, Dst, Gui, Hed, Act, Clm as well as predisposition to somatization, Som (a quantification of pain drawing) provides a useful predictive screening instrument.
Induction of Midbrain Dopaminergic Neurons from ES Cells by Stromal Cell–Derived Inducing Activity
Authors: Hiroshi Kawasaki, Kenji Mizuseki, Satomi Nishikawa, Satoshi Kaneko, Yoshihisa Kuwana, Shigetada Nakanishi, Shin-Ichi Nishikawa, Yoshiki Sasai
Journal: Neuron (2000)
Response to: ‘Does it make sense to investigate whether the offspring of people with a total knee replacement for severe primary knee osteoarthritis have a higher risk of worsening knee pain?’ by Lei<i>et al</i>
Authors: Feng Pan, Changhai Ding, Tania Winzenberg, Hussain Khan, Johanne Martel-Pelletier, Jean-Pierre Pelletier, Flavia Cicuttini, Graeme Jones
Journal: Annals of the Rheumatic Diseases (2015)

We would like to thank Lei et al 1 for their interest in and comments on our paper on the higher risk of worsening knee pain in the offspring with a family history of knee osteoarthritis (OA) as compared with control with no family history.2

First, we agree that the correlation between the radiographic OA and the presence of pain is weak and not significant in this cohort. Our group has published much of the research on this area and what does contribute to pain. Our contention is that radiographic OA is of limited significance and papers from this cohort show that. The MRI scans show many structural changes within the knee long before radiographic OA develops and these are …
Microvasculopathy in the Ocular Fundus after Bone Marrow Transplantation
Authors: Wolfgang Bernauer, Alois Gratwohl, Alexandre Keller, Basil Daicker
Journal: Annals of Internal Medicine (1991)

Objective: To determine the incidence and time course of retinal and optic-disk ischemia after bone marrow transplantation and to describe the clinical, fluorescein-angiographic, and histologic findings in patients with these ischemic fundus lesions. Design: Prospective cohort study; standardized clinical and ophthalmologic evaluation of all patients before bone marrow transplantation and 3, 6, and 12 months after transplantation (and when indicated). Setting: University hospitals in Basel, Switzerland. Patients: Consecutive patients (127) treated with allogeneic or autologous bone marrow grafts. Main Results: Thirteen of the 127 patients (10%; 95% Cl, 5% to 15%) had lesions of the ocular microcirculation. All patients had cotton-wool spots in the fundus of both eyes, and three patients also had bilateral optic-disk edema. Secondary changes included retinal hemorrhages and lipid deposits. The ischemic fundus lesions appeared during the first 6 months after transplantation and were reversible in 9 of the 13 patients. The lesions occurred only in patients who were treated with total body irradiation and were given cyclosporin A as prophylaxis for graft-versus-host disease. Conclusions: Ischemic fundus lesions are a frequent complication after bone marrow transplantation. They were only observed in patients treated with total body irradiation and cyclosporin A. This combination of therapy appears to have an additive effect on the development of ocular and possibly generalized microvascular lesions.
The obesity–asthma link in different ages and the role of Body Mass Index in its investigation: findings from the <i><scp>G</scp>enesis</i> and <i><scp>H</scp>ealthy <scp>G</scp>rowth </i><scp>S</scp>tudies
Authors: G. V. Guibas, Y. Manios, P. Xepapadaki, G. Moschonis, N. Douladiris, C. Mavrogianni, N. G. Papadopoulos
Journal: Allergy (2013)

Abstract Background To date, an obesity/asthma link is well defined in adults; however, the nature of such a link is obscure in children, partly due to Body Mass Index ( BMI ) limitations as a surrogate fat mass marker in childhood. We thus opted to investigate the association of adiposity with asthma in children of different ages, using several indices to assess fat mass. Methods Wheeze ever/in the last 12 months (current) and physician‐diagnosed asthma were retrospectively reported via questionnaire by the parents of 3641 children, participating in two cross‐sectional studies: 1626 children aged 2–5 (the Genesis Study) and 2015 children aged 9–13 (the Healthy Growth Study). Perinatal data were recorded from the children's medical records or reported by parents. Anthropometric measurements (i.e., BMI , waist/hip circumference, biceps/triceps/subscapular/suprailiac skinfold thickness) were conducted in both cohorts; bioelectric impedance analysis ( BIA ) was conducted only in preadolescent children. Results In children aged 2–5, asthma was positively correlated with conicity index, waist/hip circumference, waist‐to‐height ratio, skinfold thickness, and skinfold‐derived percentage fat mass ( P &lt; 0.05) but not BMI or BMI ‐defined overweight/obesity, after adjusting for several confounders. In children aged 9–13, asthma was positively associated with conicity index, waist circumference, waist‐to‐height ratio, skinfold thickness, skinfold‐derived percentage fat mass, BIA ‐derived percentage fat mass, BMI , and BMI ‐defined overweight/obesity, following adjustment ( P &lt; 0.05). Current/ever wheeze was not consistently associated with fat mass in either population. Conclusions Fat mass is positively linked to asthma in both 2–5 and 9–13 age spans. However, the failure of BMI to correlate with preschool asthma suggests its potential inefficiency in asthma studies at this age range.
Disorders of the Spleen: Pathophysiology and Management
Authors: Beverly Baron
Journal: JAMA (1990)

This beautifully illustrated, wellindexed 450 + -page volume presents a clear and comprehensive, yet concise, review of splenic disorders in adults and children. It begins with a discussion of normal anatomy and function, then proceeds to a review of gross and microscopic pathology in a variety of splenic disease states. Disturbed splenic function— both hyposplenism and hypersplenism—is discussed in depth. Emphasis is placed on pathophysiologic mechanisms, where known, and available clinical methods (including imaging techniques) for diagnosing the functional state of the spleen. There is detailed attention given to the workup and management of the patient with splenomegaly. Systematic review of neoplastic, storage/metabolic, infectious, and immune disorders is presented. Recommendations for treatment of asplenic individuals are included. This monograph is commended particularly for successfully relating data from the basic sciences to clinical features of disturbed splenic function. The pathology and relevant basic immunology are included not as a comprehensive review, but
Quantitative relation between gastric acid secretion and changes in urinary acid excretion.
Authors: C D Johnson, P A Harris, C Wastell
Journal: Gut (1990)

This study was designed to investigate the relations between gastric acid secretion and alkalinisation of the urine. Normal subjects underwent standard pentagastrin (6 micrograms/kg) (n = 5) and sham feeding (n = 6) tests, with additional collection of urine samples before and two and three hours after the start of the test for measurement of titratable urine acidity. Nine subjects provided urine before and two hours after a test meal. Sham feeding (n = 5) and meal (n = 6) tests were carried out in patients who had had a successful vagotomy for duodenal ulcer. There was a significant correlation of gastric acid response in the standard tests with simultaneous changes in urine acidity (r = -0.79, p less than 0.001) and also with urine acid output after the test meal, on another day (r = -0.73; p less than 0.02). The correlation was insufficient to predict gastric function from changes in urinary acidity, but there was clear separation of the results in normal subjects and patients with vagotomy. Changes in urine acidity after a standardised meal may prove to be useful as a screening test after vagotomy to select patients who are likely to have a persisting high gastric acid response to vagal stimulants.
Primary Prevention—Whose Responsibility?
Authors: ALVIN BECKER, LOUISE WYLAN, WILLIAM McCOURT
Journal: American Journal of Psychiatry (1971)

The authors believe that community mental health centers must make a commitment to develop primary prevention services for highrisk groups in their catchment areas. Boston State Hospital, in collaboration with its community and other human service agencies, has developed a program focused on the needs of children. It includes a school program, community center, family intervention unit, children's developmental workshop, court program, and a special high-risk group program. The critical need for a new alliance of human service providers is stressed.
The Impact of Health Insurance Reform on the Law Governing the Physician-Patient Relationship
Authors: Wendy E. Parmet
Journal: JAMA (1992)

AS THE health care cost and access crises deepen,<sup>1</sup>and with the arrival of a new administration in Washington, health insurance reform looks increasingly inevitable. However, despite widespread recognition that change is needed, many fear that reform will lead to increased regulation, a decline in the quality of care, and an erosion of physician autonomy and patient choice. This need not be the case. Although reform will undoubtedly change the legal climate in which health care is practiced, it may prove no more corrosive of the physician-patient relationship than continuation of the decentralized system we now have. For editorial comment see p 3479. <h3>PROPOSED REFORMS</h3> The number and variety of reforms that have been proffered is truly staggering.<sup>2</sup>Nevertheless, three broad categories warrant special consideration: single-payer proposals, employment-based proposals, and tax credit/insurance reform proposals. An example of the single-payer model is the proposal put forward by Rep Marty
Expanded polytetrafluoroethylene grafts in reconstructive arterial surgery. Preliminary report of the first 110 consecutive cases for limb salvage
Authors: Frank J. Veith, Charles M. Moss, Stanley C. Fell, Barbara A. Rhodes, Eric Somberg, Paul Weiss, Scott J. Boley, Henry Haimovici
Journal: JAMA (1978)

One hundred ten arterial reconstructions, including several new and extended bypasses, were performed with polytetrafluoroethylene (PTFE) grafts and were observed for three to 16 months. Patency rates were 100% with 15 bypasses to the femoral artery, 95% with 66 bypasses to the popliteal artery, and 76% with 29 bypasses to the arteries of the leg and foot. These encouraging preliminary results justify continued use and evaluation of PTFE as an arterial prosthesis.
Evaluation of recombinant allergens Bet v 1 and Bet v 2 (profilin) by Pharmacia CAP System in patients with pollen-related allergy to birch and apple
Authors: R. E. Rossi, G. Monasterolo, D. Operti, M. Corsi
Journal: Allergy (1996)

Sixty-five patients presenting either rhinoconjunctivitis or asthma and sensitized to pollens of trees of the order Fagales were studied by the Pharmacia CAP system in order to assess specific IgE for the important birch pollen allergens Bet v 1 and Bet v 2. All 65 subjects reacted to at least one of the recombinant birch allergens: 43% to Bet v 1, 30.7% to Bet v 2, and 26% to both. Patients monosensitized to birch did not react to Bet v 2. Of patients with a history of oral allergy syndrome after eating apples, 16/28 (57%) reacted to Bet v 1; among 20 polysensitized subjects presenting oral allergy syndrome after consumption of apple, four reacted to Bet v 2 (20%). Among patients with IgE against both recombinant allergens, six (35.30%) presented symptoms of allergy after eating apples. Our results indicate that sensitization to Bet v 1 is specific for birch and apple allergies, whereas sensitization to Bet v 2 is common in polysensitized patients.
The effect of calcium ion concentration on osteoblast viability, proliferation and differentiation in monolayer and 3D culture
Authors: Shinichi Maeno, Yasuo Niki, Hideo Matsumoto, Hideo Morioka, Taku Yatabe, Atsushi Funayama, Yoshiaki Toyama, Tetsushi Taguchi, Junzo Tanaka
Journal: Biomaterials (2005)
A 21-year-old woman with menstrual irregularity
Authors: A. Davis
Journal: JAMA (1997)

Dr Daley:  Ms K is a 21-year-old single college student who has had difficulty with her menses for a year. She moved to this country in late 1995 to attend college. She studies education and lives with a friend in Boston. She has commercial indemnity insurance.  Ms K experienced menarche at the age of 12 years and had regular periods every month lasting about 4 days. Mild cramps accompanied her menses, and she had bloating and breast tenderness prior to them. She has never been on birth control pills and has never been pregnant. Before coming to Boston, she was sexually active, used condoms, and received 2 shots (she does not remember the medication) for birth control at 3-month intervals, with the most recent injection in April or May 1995. She menstruated normally in July through October, but then began bleeding continuously in November 1995. Bleeding varied from heavy to
Ovulation Suppressors, Psychological Functioning, and Marital Adjustment
Authors: Frederick J. Ziegler
Journal: JAMA (1968)

In a series of 39 couples (studied intensively over a four-year period which began just before their first use of oral contraceptives) 15 wives used the pills throughout the study, while 9 discontinued them permanently. Side effects were equivalent in both of these groups and were therefore nonpredictive of who would stop taking the pills. The wives who continued to take the pills were relatively more responsible and more intellectually and socially effective than their husbands. Relative to their husbands, they also preferred sexual intercourse more often than did the wives who discontinued. Husbands of the wives who discontinued were more concerned about propriety and reputation than were husbands of the wives who continued. Psychological functioning of both husband and wife tended to improve in the couples continuing the use of the pills as compared to the ones who did not. Of special note, depression decreased and sexual interest increased in those who continued. Three unplanned pregnancies in the ten women who discontinued the pills permanently or temporarily would indicate a need for caution in the recommendation of ovulation suppressor contraception for couples in which the husband is clearly the dominant spouse.