tbuckley/cabot-search huggingface dataset:
Biomedical Implications of Advanced Research and Technology
Authors: Merlin K. DuVal
Journal: JAMA (1972)

Extraordinary advances in the biological and medical sciences in this century have raised serious ethical, social, and legal problems. Some of these problems are associated with: control of birth rates, "genetic engineering," organ transplantation, prolongation of dying, selective life saving, and behavior modification through drugs. The US Department of Health, Education, and Welfare has engaged in a continuing examination and discussion of the questions posed by clinical investigation in research conducted or funded by the National Institutes of Health. Several groups in the private sector have considered the legal, social, and ethical implications of advances in the health sciences. All this represents development of responsible decision points within our society for addressing and treating the issues and implications associated with advanced biomedical research.
Complete Genetic Correction of iPS Cells From Duchenne Muscular Dystrophy
Authors: Yasuhiro Kazuki, Masaharu Hiratsuka, Masato Takiguchi, Mitsuhiko Osaki, Naoyo Kajitani, Hidetoshi Hoshiya, Kei Hiramatsu, Toko Yoshino, Kanako Kazuki, Chie Ishihara, Shoko Takehara, Katsumi Higaki, Masato Nakagawa, Kazutoshi Takahashi, Shinya Yamanaka, Mitsuo Oshimura
Journal: Molecular Therapy (2009)

Human artificial chromosome (HAC) has several advantages as a gene therapy vector, including stable episomal maintenance that avoids insertional mutations and the ability to carry large gene inserts including the regulatory elements. Induced pluripotent stem (iPS) cells have great potential for gene therapy, as such cells can be generated from the individual's own tissues, and when reintroduced can contribute to the specialized function of any tissue. As a proof of concept, we show herein the complete correction of a genetic deficiency in iPS cells derived from Duchenne muscular dystrophy (DMD) model (mdx) mice and a human DMD patient using a HAC with a complete genomic dystrophin sequence (DYS-HAC). Deletion or mutation of dystrophin in iPS cells was corrected by transferring the DYS-HAC via microcell-mediated chromosome transfer (MMCT). DMD patient- and mdx-specific iPS cells with the DYS-HAC gave rise to differentiation of three germ layers in the teratoma, and human dystrophin expression was detected in muscle-like tissues. Furthermore, chimeric mice from mdx-iPS (DYS-HAC) cells were produced and DYS-HAC was detected in all tissues examined, with tissue-specific expression of dystrophin. Therefore, the combination of patient-specific iPS cells and HAC-containing defective genes represents a powerful tool for gene and cell therapies. Human artificial chromosome (HAC) has several advantages as a gene therapy vector, including stable episomal maintenance that avoids insertional mutations and the ability to carry large gene inserts including the regulatory elements. Induced pluripotent stem (iPS) cells have great potential for gene therapy, as such cells can be generated from the individual's own tissues, and when reintroduced can contribute to the specialized function of any tissue. As a proof of concept, we show herein the complete correction of a genetic deficiency in iPS cells derived from Duchenne muscular dystrophy (DMD) model (mdx) mice and a human DMD patient using a HAC with a complete genomic dystrophin sequence (DYS-HAC). Deletion or mutation of dystrophin in iPS cells was corrected by transferring the DYS-HAC via microcell-mediated chromosome transfer (MMCT). DMD patient- and mdx-specific iPS cells with the DYS-HAC gave rise to differentiation of three germ layers in the teratoma, and human dystrophin expression was detected in muscle-like tissues. Furthermore, chimeric mice from mdx-iPS (DYS-HAC) cells were produced and DYS-HAC was detected in all tissues examined, with tissue-specific expression of dystrophin. Therefore, the combination of patient-specific iPS cells and HAC-containing defective genes represents a powerful tool for gene and cell therapies.
598 IMPACT OF LOW-LEVEL HEPATITIS C VIRAEMIA AT WEEK 24 ON HCV TREATMENT RESPONSE IN GENOTYPE 1 PATIENTS
Authors: C. Baleriola, W. Rawlinson, S. Chaverot, S. Stelzer-Braid, M. Yoshihara, B. Rizkalla, D. Dubois, W. Sievert, G. McCaughan, D.H.G. Crawford, M. Weltman, W.S.C. Cheng, G.J. Dore, S. Roberts
Journal: Journal of Hepatology (2009)
Indian state bans tobacco based chewing products
Authors: S. Kumar
Journal: BMJ (2002)

In an important anti-tobacco move, the state government of Maharashtra has banned the sale, display, manufacture, and distribution of gutka and paan masala, two very popular chewable tobacco based products.

Even though one type of Paan masala does not contain tobacco, it containts betel nut, which is also a carcinogen.

The state of Maharashta, which covers Mumbai, has 40 manufacturing plants for gutka and paan masala.

“The ban will become effective from 1 August 2002, …
Racial Misclassification of Native Americans in a Surveillance, Epidemiology, and End Results Cancer Registry
Authors: F. Frost, V. Taylor, E. Fries
Journal: JNCI Journal of the National Cancer Institute (1992)

The cancer incidence for all sites has been reported to be lower in Native Americans than in White Americans. Concerns have been expressed, however, that the observed low incidence may be a result of inaccurate reporting of race.The objective of this study was to investigate the extent to which racial misclassification may contribute to the observed low cancer incidence among Native Americans.A registry of individuals eligible to receive medical services funded by the Indian Health Service was linked by computer to the Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry.Only 137 (60%) of the patients with invasive cancer registered with the Indian Health Service and for whom race was recorded were identified as Native Americans in the SEER registry. Similarly, 55 (69%) of 80 in situ cervical cancer case patients were classified as Native American. A strong association was observed between Native-American blood quantum level and racial misclassification.The results of this study indicate that the observed low cancer incidence in Native Americans relative to Whites in the northwest United States is at least partially attributable to racial misclassification in the SEER cancer registry.
Abstract 2287: Inhibition of microRNA-32 leads to decreased expression of the survival-enhancing scaffold protein hKSR2 in human myeloid leukemia cells treated with vitamin D derivatives
Authors: Xuening Wang, Xiangwen Chen-Deutsch, Jonathan S. Harrison, George P. Studzinski
Journal: Cancer Research (2012)

Abstract 1,25-dihydroxyvitamin D3 (1,25D) has potential for treatment and/or prevention of human AML by inducing terminal differentiation of AML cells to monocyte-like phenotype, but the mechanisms underlying this action are not fully understood. We hypothesized that one or more microRNAs (miRNAs) known to control mouse hematopoiesis and lineage commitment may contribute to the known ability of 1,25D to control the malignant phenotype. We found that miR181a and miR32 both participate in the differentiating effects of 1,25D, with effects on cellular levels of cell cycle regulator p27Kip1 and the pro-apoptotic protein Bim, respectively. Here we report that in human AML cells modulation of 1,25D-induced expression of miR32 and miR181a can result in the down-regulation of the abundance of the scaffold protein hKSR2, which is associated with inhibition of differentiation. This supports the concept that hKSR2 is under miRNA control in AML cells. However, ectopic expression of miR32 had little effect on hKSR2 protein levels, suggesting that there is an indirect effect of miR32 on hKSR2 expression, and that intracellular levels of the intermediary regulators are already at saturation levels. Since hKSR2 protein has cell survival-enhancing properties, 1,25D-induced miRNAs and hKSR2 changes may reduce the therapeutic efficacy of 1,25D and analogs in human AML, especially when vitamin D analogs are combined with conventional cytotoxic anti-leukemia agents. This warrants consideration in the design of clinical trials. (This research was supported by NIH grant R01 CA 044722-22 from the National Cancer Institute). 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 2287. doi:1538-7445.AM2012-2287
Suppurative Otitis Media: Perforation of Mastoid: Trephining and Exploration of the Temporo-Sphenoidal Lobe
Authors: J. Black
Journal: BMJ (1887)

was stitched to the abdominal wall, a drainage-tube inserted, and dry dresing applied.For a few days the urine was black like porter, but then it cleared, the patient made a capital recovery, and remains perfectly well.
Adjuvant intra-arterial injection of iodine-131–labeled lipiodol after resection of hepatocellular carcinoma
Authors: Eveline Boucher, Stéphane Corbinais, Yan Rolland, Patrick Bourguet, Dominique Guyader, Karim Boudjema, Bernard Meunier, Jean-Luc Raoul
Journal: Hepatology (2003)

The high rate of recurrence after surgical resection of hepatocellular carcinoma (HCC) is a major therapeutic challenge. Postoperative injection of 131–iodine–labeled lipiodol ( 131 I–Lip) into the hepatic artery has been proposed as adjuvant treatment (Lau et al.). We analyzed 2 retrospective series of matched patients treated in our unit before and after addition of 131 I–Lip adjuvant therapy to our standard surgical strategy. Thirty–eight patients who had undergone surgical resection of HCC after January 1999 were given adjuvant intra–arterial injection of 131 I–Lip after surgery. These patients were matched with 38 other patients who had undergone surgical resection only between January 1997 and January 1999. The frequency of recurrences, disease–free rates, and overall survival rates were compared. The 2 groups were similar for clinical, biologic, or histologic parameters studied and Cancer Liver Italian Program scores. There were 15 recurrences in the group without adjuvant treatment and 9 in the group with 131 I–Lip adjuvant treatment. The 1–, 2–, and 3–year disease–free survival rates (±95% confidence interval) were different ( P &lt; .02): 94.7% ± 3.6%, 83.7% ± 6.1%, and 68.4% ± 9.7%, respectively, in the 131 I–Lip group versus 73.7% ± 7.1%, 54.3% ± 8.2%, and 41.5% ± 10.5% in the surgery group. The 1–, 2–, and 3–year survival rates (±95% confidence interval) also were different ( P &lt; .02): 94.7% ± 3.6%, 91.7% ± 4.6%, and 91.7% ± 4.6%, respectively, in the 131 I–Lip group versus 94.7% ± 3.6%, 71.3% ± 7.8%, and 49.9% ± 10% in the surgery group. In conclusion, this retrospective analysis supports the promising contribution of postoperative injection of 131 I–Lip after resection of HCC. A randomized study including more patients would be necessary to confirm its contribution to therapeutic management.
THE EARLIER, THE BETTER
Authors: Tomoki Shokawa, Koichi Tanigawa, Ken Ishibashi, Takenori Okada, Kenji Nishioka, Yukiko Nakano, Hiroki Teragawa, Futoshi Tadehara, Hideya Yamamoto, Tkafumi Ishida, Yasuki Kihara
Journal: Journal of the American College of Cardiology (2010)
Spartin Regulates Synaptic Growth and Neuronal Survival by Inhibiting BMP-Mediated Microtubule Stabilization
Authors: Minyeop Nahm, Min-Jung Lee, William Parkinson, Mihye Lee, Haeran Kim, Yoon-Jung Kim, Sungdae Kim, Yi Sul Cho, Byung-Moo Min, Yong Chul Bae, Kendal Broadie, Seungbok Lee
Journal: Neuron (2013)
Activation of the oxidative burst in human monocytes is associated with inhibition of methionine-dependent methylation of neutral lipids and phospholipids.
Authors: E Bonvini, P Bougnoux, H C Stevenson, P Miller, T Hoffman
Journal: Journal of Clinical Investigation (1984)

Chemotaxis and generation of the oxidative burst by phagocytes are among the biological functions thought to require methylation reaction(s) for their expression. The present study investigated the effect of different stimuli of the oxidative burst on lipid methylation by human elutriated monocytes as measured by methyl group incorporation from [methyl-3H]methionine into both phospholipid and neutral lipid extracts. Normal monocytes, incubated at 37 degrees C for 1 h with 2 microM methionine, incorporated 10.2-fmol/10(6) cells and 73.6-fmol/10(6) cells of methyl groups into neutral lipids and phospholipids, respectively. Stimulators of the respiratory burst, such as the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine, the tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate, and the calcium ionophore, A23187, decreased the incorporation of methyl groups into both neutral lipids and phospholipids in a similar manner. Increasing the concentration of methionine in the medium reversed or attenuated the inhibition achieved at lower levels. An inverse relationship existed between the degree of methylation and the extent of stimulation of the oxidative burst, measured as superoxide anion (O-2) release. Stimulated monocytes oxidized methionine to methionine sulfoxide (which cannot act as a methyl-donor), and this was dependent on activation of the respiratory burst. Elimination of the accumulated methionine sulfoxide by replacement of the medium or by prevention of extracellular methionine oxidation by catalase did not effectively restore the normal level of methylation in stimulated cells, and the reduced methylation was not primarily related to a defective methionine uptake by stimulated monocytes. These data suggest that intracellular events related to activation of the respiratory burst are responsible for the decreased lipid methylation in stimulated cells, possibly by their leading to intracellular formation of methionine sulfoxide and by their limiting the availability of methyl-donor. This mechanism may be of potential relevance for the expression of biological functions where methionine-dependent reactions are involved.
808 LIVER FIBROSIS AND THE RISK OF HEPATIC VENO-OCCLUSIVE DISEASE IN CHILDREN WITH BETA THALASSEMIA DISEASE UNDERGOING ALLOGENEIC HAEMATOPOIETIC STEM-CELL TRANSPLANTATION
Authors: V. Chongsrisawat, P. Peerataweepong, N. Wisedopas, I. Nuchprayoon, Y. Poovorawan
Journal: Journal of Hepatology (2010)
Serial homicide by doctors: Shipman in perspective
Authors: H. G Kinnell
Journal: BMJ (2000)

In a two-lever appetitively reinforced bar-pressing task, one group of rats learned a phenobarbital vs. saline discrimination. Groups 2 to 4 were reinforced for pressing one lever when given phenobarbital and for pressing the other level when given saline or any one of three drugs. In Group 2, the other drugs were the stimulants amphetamine, cocaine and bemegride. In Group 3, the other drugs lacked either strong stimulant or depressant effects (fentanyl, nicotine and cyclazocine). In Group 4, the other drugs were the depressants ethanol, chlordiazepoxide and ketamine. All rats learned the required multiple drug (phenobarbital vs. other) discrimination after one to four training sessions per drug. After discrimination training was completed, tests for substitution with various depressant drugs showed that the degree to which these drugs substituted for phenobarbital differed greatly across groups. Substitution was most complete in rats trained with phenobarbital vs. saline and least complete when the other training drugs were depressants. The results indicate that the degree of specificity produced by phenobarbital vs. other drug discrimination training can be systematically altered by varying the drugs included in the other category.
Appointment and mobility of general practitioners.
Authors: C D Side
Journal: BMJ (1987)

bubbles are visible to the operator when blood is drawn into the microcuvette. The most likely source of error, or misleading results, would be poor mixing of the full blood count sample before analysis. The distribution of  in fig 2 supports this assumption. An erroneously high or low haemoglobin result would be obtained no matter how often the same microcuvette was placed in the machine. The absence of high or low outliers in the HemoCue results performed in a laboratory (fig 1) may be explained because all laboratory samples were thoroughly mixed on a rotating rack before sampling. The health centre does not possess a sample mixer and the practice nurses rotate each full blood count tube by hand. If a 4 ml whole blood sample were incorrectly mixed before withdrawal of a 10 |jil microcuyette sample then falsely high or low haemoglobin results would be obtained depending on which part of the original 4 ml sample was subsampled. The results of this study emphasise how important it is to evaluate equipment intended for use in primary care within primary care by primary care staff. Practices considering using a HemoCue, or any similar portable haemoglobinometer, should also use a rotating mixer for samples. An alternative would be to incorporate some kind of mixer on the haemoglobinometer itself, or to restrict the use of the machine to samples obtained by the finger prick method alone. The operating instructions should also be modified to reflect the importance of this potential error. Probably if the HemoCue was operated by junior hospital staff in ward side rooms similar problems to those encountered by the health centre staff would occur.
Balancing benefits and harms in health care: Editor's choice was sensationalist but not true
Authors: Bob Bury
Journal: BMJ (2004)

EDITOR—I have for a long time thought that one of the chief obstacles to the public's understanding of medicine is the inability of the average punter to understand the concepts of probability and risk-benefit analysis that underpin most of the treatment decisions we make, and our failure as a profession to dispel that ignorance.

It was disappointing to read Smith's Editor's …
Tc-99m Sestamibi and Gated Blood Pool Scintigraphy in Localization of Ectopic Mediastinal Parathyroid
Authors: TROY A. JONES, MARY WOOD
Journal: Clinical Nuclear Medicine (1997)

A 38-year old man had persistent hyperparathyroidism despite two previous (neck) parathyroidectomies. Subsequently, ectopic parathyroid gland activity in the mediastinum was demonstrated on a Tc-99m sestamibi scan. The tumor localization in the mediastinum was confirmed by placing a "cold" marker over the focal parathyroid activity, and then by performing a gated blood pool study, which outlined the right heart, pulmonary artery, and the left heart and ascending aorta. At surgery, two small ectopic parathyroid glands were found in the aortopulmonary window, where the marker was placed. These represented pathology proven parathyroid adenomas.
Clinical oncology information network: Population based registries remain valuable
Authors: M C Gulliford, R Carr, C Poynton, D R Glover, P Quartey
Journal: BMJ (1994)

EDITOR, - S J Karp describes initiatives by clinical oncologists to evaluate their work in cancer treatmentcentres in Britain.1 This is an important step forward, but many patients with cancer are treated by general surgeons, physicians, or geriatricians in district hospitals. Sometimes cancer is diagnosed for the first time at postmortem examination. It is important to evaluate the treatment of all patients with cancer and not just those referred for specialist treatment, particularly in a system in which access to care is limited. Clinic based information systems may help to evaluate treatment provided by particular institutions but give an incomplete picture of care provided for people with cancer in Britain. Karp is therefore incorrect to dismiss the use of data from cancer registries in the evaluation of cancer treatment. Population based registries are important sources of data for evaluating cancer care in Britain. …
Mesoporous silicon microparticles for oral drug delivery: Loading and release of five model drugs
Authors: J. Salonen, L. Laitinen, A.M. Kaukonen, J. Tuura, M. Björkqvist, T. Heikkilä, K. Vähä-Heikkilä, J. Hirvonen, V.-P. Lehto
Journal: Journal of Controlled Release (2005)
Rubber-glove Dermatitis
Authors: H. T. H. Wilson
Journal: BMJ (1960)

Eczema of the hands is a chronic condition the aetiology of which is often obscure, the prognosis uncertain, and treatment largely palliative.Some cases, however, can be traced to allergic contact sensitivity, and in these the outlook is greatly improved, for a specific cause may be found and removed.Downing (1933) reported seven cases of dermatitis of the hands, all attributable to one particular brand of rubber gloves, while other examples were described by Traub (1946) and Bettley (1952).Leider et al. (1952), investigating 124 cases of sensitivity to rubber articles, found that 17 of them were due to gloves, while Sidi and Hincky (1954) were able to collect as many as 102 cases of rubber-glove dermatitis, most of them being caused by red household gloves.Bonnevie and Marcussen (1944) found that allergy to rubber accounted for 2 % of all their cases of sensitivity eczema.
The Lame Princess: A Study of the Remission of Psychiatric Symptoms Without Treatment
Authors: MORTON BEISER
Journal: American Journal of Psychiatry (1972)

As part of the Stirling County study of sociocultural factors affecting psychiatric symptoms, selected cases are being examined in an attempt to shed light on the process of recovery. The subject presented here (a fictional composite of several cases) not only lost the symptoms that had distressed her for much of her life but effected a more mature adjustment. This is explained with emphasis on the concepts of latent role repertoire, role change, and role rehearsal.
APPENDICITIS.DEDUCTIONS FROM TWO HUNDRED AND SEVEN CASES OPERATED ON, WITH TABULATED REPORT.
Authors: JOHN B. MURPHY
Journal: JAMA (1895)

I will endeavor to give a short outline of the various conditions found in operating for appendicitis: 1. Where the abdominal wall is infiltrated, and the abscess is opened without opening the unaffected portion of the peritoneum, there may be:<i>a</i>, a small circumscribed abscess with the appendix forming part of the wall;<i>b</i>, a small abscess with a tract leading to a larger abscess deeper;<i>c</i>a large abscess filling the iliac fossa, containing fecal concretions, or a gangrenous appendix floating in pus, all closed in with firm adhesions. (This condition never exists in the early stage, and in this class of cases the adhesions protecting the peritoneum should not be broken to remove the appendix);<i>d</i>, there may be multiple abscesses with no connecting sinuses. This is a comparatively rare condition. In one of my cases, a second abscess was not opened and the patient died of pyemia