tbuckley/cabot-search huggingface dataset:
Transplantation of cultured thymic fragments. II. Results in nude mice.
Authors: R Hong, H Schulte-Wissermann, E Jarrett-Toth, S D Horowitz, D D Manning
Journal: The Journal of Experimental Medicine (1979)

Nine nude mice were transplanted with cultured thymic fragments derived from syngeneic (three recipients) or allogeneic (six recipients) sources. All transplanted mice survived for periods of up to 8-10 mo thereafter, at which time they were sacrificed. Weight gain had been progressive and the animals were in excellent health. Four nontransplanted littermates housed in the same cages died at the age of 4 mo. In the nontransplanted mice, the usual deficits of T and B cells were observed. In transplanted mice, normalization of IgG1 and IgA levels as well as IgG antibodies to sheep erythrocytes and precipitating antibodies to rabbit serum occurred. Lymphocyte counts and Thy-1 bearing cells increased to approximately 50% of normal values. Proliferative responses to phytohemagglutinin and concanavalin A, mixed leukocyte reactivity, and cell-mediated lympholysis were variably restored from approximately 10-100% of normal. Attained responses were the same in recipients of syngeneic or allogeneic tissues and these, in turn, were equal or superior to responses measured in animals transplanted with whole noncultured thymuses. Skin grafts from third party donors were vigorously rejected, whereas those derived from second party (allogeneic thymus donor strain) may have been accepted or slowly rejected. Cultured thymic fragments, consisting primarily of epithelial elements, can effectively repair the thymic deficiency of nude mice. Experiments to date do not indicate that syngeneic tissues enjoy an advantage over allogeneic grafts in this restoration procedure.
"Adverse Drug Reaction Bulletin"
Authors: D M Davies
Journal: BMJ (1986)

Australia supports the concept that lesions in Australia have a better prognosis than those in Oxford because they are diagnosed at an earlier stage owing to greater public and professional awareness.4At Queen's University, Belfast, we have now started a teaching programme to improve the recognition ofmelanomas by medical students.We plan to extend this into the postgraduate educational programme for general practitioners and other doctors.The public should also be made more aware of the possible dangers inherent in certain types of pigmented lesions and the curability of melanoma in its early stages.Un- necessary deaths can be prevented.
EXPERIMENTAL ERYTHROBLASTOSIS FETALIS IN RABBITS
Authors: Aaron Kellner, Emily F. Hedal
Journal: The Journal of Experimental Medicine (1953)

A pair of blood group factors, designated G and g, was identified in rabbits by serological means. These factors were found to be alleles, and one or the other or both of them were regularly present in the red cells of every one of a large number of mongrel and inbred rabbits. The factors were not demonstrable in other tissue cells or in the body fluids. They were capable of stimulating the formation of specific immune isoantibodies when repeatedly injected into appropriate rabbits. In most instance both agglutinating and coating antibodies to the G or g factors were present in a given antiserum. The coating antibodies-which did not act as true blocking antibodies-were detected by means of an antiglobulin test (Coombs test), or by means of specific cells modified by the action of trypsin. The antibodies were heat-stable and were active over a wide temperature range; and under suitable conditions, they proved to be potent hemolysins and also capable of fixing complement. The characteristics of the antigens and antibodies of the rabbit G-g system bear a striking resemblance to those of the Rh-Hr system of man.
Diagnosis of Chlamydia trachomatis Genitourinary Infections
Authors: WALTER E. STAMM
Journal: Annals of Internal Medicine (1988)

The lack of a widely available diagnostic test for genital infections with Chlamydia trachomatis, coupled with their often nonspecific clinical nature, have been important factors contributing to the increasing incidence of these infections. Recent studies have more clearly defined the clinical manifestations of C. trachomatis infections, especially mucopurulent cervicitis and pelvic inflammatory disease. In addition, methods for the direct detection of chlamydial antigen in genital secretions have been developed. Although less sensitive than traditional cultural methods, these noncultural methods are more widely available than cultures and can facilitate the earlier recognition and more specific diagnosis of chlamydial genital infections. This article reviews these recent developments and outlines specific applications of tests for diagnostic purposes and for screening of high-risk populations.
Lung Function 5 yr after Lung Volume Reduction Surgery for Emphysema
Authors: ARTHUR F. GELB, ROBERT J. McKENNA, MATTHEW BRENNER, JOEL D. EPSTEIN, NOE ZAMEL
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Current datum more than 2 yr after lung volume reduction surgery (LVRS) for emphysema is limited. This prospective study evaluates pre-LVRS baseline and 5-yr results in 26 symptomatic patients (mean age 67 +/- 6 yr) (mean +/- SD) who underwent bilateral, targeted upper lobe stapled LVRS using video-assisted thoracoscopy. Baseline forced expiratory volume in 1 s (FEV(1)) was 0.7 +/- 0.2 L (mean +/- SD), 29 +/- 10% predicted. Following LVRS, with none lost to follow-up, mortality due to respiratory failure at 0.5, 1, 2, 3, 4, and 5 yr was 4%, 4%, 19%, 31%, 46%, and 58%, respectively. Increase above baseline for FEV(1) > 200 ml and/or FVC > 400 ml at 1, 2, 3, 4, and 5 yr post-LVRS was noted in 73%, 46%, 35%, 27%, and 8% of all patients; decrease in dyspnea grade >/= 1 in 88%, 69%, 46%, 27%, and 15%; and elimination of initial oxygen dependence in 18 patients in 78%, 50%, 33%, 22%, and 0%, respectively. Expiratory airflow improved due to the increase in both lung elastic recoil and small airway intraluminal caliber. Five patients decreased FEV(1) 141 +/- 60 ml/yr and FVC 102 +/- 189 ml/yr over 3.8 +/- 1.2 yr post-LVRS, similar to their pre-LVRS rate of decline. In the 11 patients who survived 5 yr, at 0.5-1.0 yr post-LVRS peak increase in FEV(1) was 438 +/- 366 ml, with a decline of 149 +/- 157 ml the following year and 78 +/- 59 ml/yr over 4.0-4.5 yr. Bilateral LVRS provided palliative clinical and physiological improvement in 9 of 26 patients at 3 yr, 7 at 4 yr, and 2 at 5 yr.
Should colonoscopy be the first investigation for colonic disease?
Authors: D. Martin
Journal: BMJ (1988)

Randomised clinical trials guard against over- optimism likely to arise from uncontrolled experiments, where bias is easily introduced.It is not true that no major advances have arisen from randomised trials in obstetrics.Two important examples are the use of corticosteroids to pre- vent the respiratory distress syndrome and the use of anti-D to prevent rhesus isoimmunisation.Furthermore, several disasters have occurred because randomised trials were not carried out, including the well known epidemic of retrolental fibroplasia.2More generally, the widespread use of inferior research designs leads to confusion in published medical reports.Of course, it is known that a few people cheat when carrying out randomised trials, but that is a reason for trying to design trials in such a way as to make such fiddling impossible, not for abandoning clinical trials completely.Randomised clinical trials are just one way of doing research and constitute a small minority of all research carried out.No one would say that all research should be in the form of randomised trials, but not to perform one when it is both possible and desirable is foolish and arguably unethical.
Exit, pursued by a carer: an opera about Alzheimer's disease
Authors: A. Convey
Journal: BMJ (2010)

Alison Convey gets a fresh perspective on Alzheimer’s disease through the medium of opera

The Lion’s Face is an opera about dementia. Immediate visions of elderly sopranos shuffling across the stage? Or exiting pursued by a carer, never to be found again? Far from it. An unlikely sounding concept, The Lion’s Face is a piece of painstaking research and artistic imagination by the composer Elena Langer and the poet Glyn Maxwell. Charting the story of Mr D, a patient with dementia in a care home, it is the product of an extraordinary collaboration between the creative team at The Opera Group and the National Institute for Health Research’s biomedical research centre for mental health, which is led by Simon Lovestone. The title of the piece refers to “leonine impassivity” of facial expression, a description associated with several conditions, including Alzheimer’s diseases. With a million people in Britain likely to have Alzheimer’s disease by 2025, the opera is an earnest endeavour to highlight and reflect on one of our society’s most daunting medical problems.

The partnership between The Opera Group and Lovestone’s team began early in the creative process. The writer, director, and composer were given access to the diverse activities of the research centre, including visits to laboratories, …
Reply to S. Girnius et al
Authors: Giovanni Palladini, Angela Dispenzieri, Morie A. Gertz, Shaji Kumar, Ashutosh Wechalekar, Philip N. Hawkins, Stefan Schönland, Ute Hegenbart, Raymond Comenzo, Efstathios Kastritis, Meletios A. Dimopoulos, Arnaud Jaccard, Catherine Klersy, Giampaolo Merlini
Journal: Journal of Clinical Oncology (2013)

CR group), PR was 51% (95% CI, 24% to 74%; P ϭ .005),and NR was 42% (95% CI, 17% to 65%; P Ͻ .001).Patients with a PR had inferior survival compared with those with a VGPR (P ϭ .0287),but similar survival when compared with those with NR (P ϭ .3907).Median EFS was similar for CR and VGPR (63 v 60 months; P ϭ .1909),whereas it was significantly lower for PR and NR (21 and 7 months, respectively).The EFS for PR was different from VGPR (P ϭ .001)and NR (P ϭ .0175).Patients achieving a CR or VGPR after HDM/SCT, as defined by the new criteria, 1 had indistinguishable OS and EFS, with median OS exceeding 9 years.These results are similar to our previous observation that PR with a greater than 90% reduction in serum-involved FLC was associated with a similar OS compared with patients in hematologic CR. 4 VGPR selects the subset of patients without a CR who have durable clinical remission and survival and do not need additional therapy until progression.We are unable to detect an OS difference between PR and NR, although there may be a selection bias, given that patients with NR were presumably less likely to be alive for a 1-year evaluation and were excluded from the analysis.There are limitations in our analysis.First, serum FLCs were not measured regularly before 2003, so compared with our original report, 3 thesurvivalisbasedmoreonestimatesthanactuarialsurvival.Second,our analysis occurred at 1 year, whereas Palladini et al 1 assessed serum FLC responses at 6 months.In our previous report, 3 19% of patients (81 of 421) died before a 1-year evaluation, so patients who were intolerant to therapy or had more aggressive disease were excluded.Last, only 140 patients met inclusion criteria, a number likely too small to detect subtle differences, particularly in the PR and NR groups, which comprised only 15 and 16 patients, respectively.Nonetheless, we conclude that the new response criteria have prognostic value in patients undergoing HDM/ SCTwhoareevaluatedforresponseat1year.Withthistreatment,patients achieving a VGPR have an excellent OS and EFS, indistinguishable from those achieving a CR.
Primary Bleeding from the Small Intestine in Adults
Authors: Donald K. Brief
Journal: JAMA (1963)

Special study of the cause of hemorrhage was made in 16 cases of major bleeding from the mesenteric parts of the small intestine in adults. The cause was found to be a tumor in eight cases, a jejunal ulcer in three, jejunal diverticulum in one, ileal (Meckel's) diverticulum in one, telangiectasia in one, granuloma secondary to a Witzel enterostomy in one, and blind pouches created by a side-to-side ileoileostomy in one. There was no specific clinical pattern associated with these hemorrhages. The diagnosis was established by x-ray examination after ingestion of barium, by intubation, and by surgical exploration. Surgical management included replacement of lost blood and early operation if replacement was necessary at a rate of 500 ml/8 hr.
Toxic Range of Bromide Level
Authors: Alex J. Arieff
Journal: JAMA (1962)

<h3>To the Editor:—</h3> I was interested in the answer to the question by Dr. Walter Weinberger—"What is the toxic range of the bromide level in blood and spinal fluid?" The information cited—75 mg. per 100 ml.—hardly registers any bromide in the blood at all. It is certainly more than the normal amount, but has nothing to do with toxicity. In well-controlled studies in the literature on the use of bromide in epilepsy, most patients show no toxic effect at well over 200 mg. Toxic levels are usually considered to be from 250 to 300 mg.; however, if a patient shows toxic signs, and his blood bromide is 200 mg. or over, toxicity should be considered. In psychotherapy or in the treatment of epilepsy, it is well to achieve a level of 150 to 200 mg.; otherwise there is no therapeutic value.
Mature B-cell lymphoblastic leukemia with MLL rearrangement: an uncommon and distinct subset of childhood acute leukemia
Authors: N Blin, F Méchinaud, P Talmant, R Garand, P Boutard, N Dastugue, E A McIntyre, J L Harousseau, H Avet-Loiseau
Journal: Leukemia (2007)
Current Therapeutic Concepts in Diabetic Hypertension
Authors: A N Peiris, A B Gustafson
Journal: Diabetes Care (1986)

Diabetes mellitus and hypertension are both prevalent in the adult population. The development of hypertension in the diabetic patient is likely to increase the morbidity and mortality in a subgroup already at high risk for atherosclerosis and deserves special consideration. Several studies have confirmed the beneficial effects of antihypertensive therapy on complications such as diabetic nephropathy. This emphasizes the importance of normalizing blood pressure in the diabetic population. It has been suggested that the threshold for initiating antihypertensive therapy should be lower in diabetic patients. All antihypertensive agents have potential disadvantages in patients with diabetes. The commonly encountered effects include deterioration of diabetic control, sexual dysfunction, electrolyte imbalance, and lipid disorders. The adverse effects of these agents on serum lipids have been implicated in the less-than-expected reduction in coronary heart disease noted in some studies. The recent Lipid Research Council study has emphasized the importance of elevated lipid levels and increased cardiovascular mortality. Antihypertensive therapy has advanced rapidly in the last 5 yr. The special problems in the treatment of hypertension within the diabetic population are now receiving greater attention. Undesirable biochemical side effects of drugs used to treat hypertension have become publicized, and the long-term consequences of these abnormalities are under critical scrutiny. The new antihypertensive medications offer exciting alternative approaches to the more traditional agents with less chance of significant metabolic side effects.
Monitoring and evaluation of programmes to prevent mother to child transmission of HIV in Africa
Authors: Richard Reithinger, Karen Megazzini, Stephen J Durako, D Robert Harris, Sten H Vermund
Journal: BMJ (2007)

Many countries are expanding the coverage of programmes to prevent mother to child transmission of HIV. Although the need is unquestionable, <b>Richard Reithinger and colleagues </b>are concerned that without true measures of effectiveness we may not be making the best use of resources
Parthenolide Inhibits Tubulin Carboxypeptidase Activity
Authors: Xavier Fonrose, Frédéric Ausseil, Emmanuelle Soleilhac, Véronique Masson, Bruno David, Isabelle Pouny, Jean-Christophe Cintrat, Bernard Rousseau, Caroline Barette, Georges Massiot, Laurence Lafanechère
Journal: Cancer Research (2007)

Abstract Microtubules are centrally involved in cell division, being the principal components of mitotic spindle. Tubulin, the constituent of microtubules, can be cyclically modified on its α-subunit by enzymatic removal of the COOH-terminal tyrosine residue by an ill-defined tubulin carboxypeptidase (TCP) and its readdition by tubulin tyrosine ligase (TTL). We and others have previously shown that suppression of TTL and resulting accumulation of detyrosinated tubulin are frequent in human cancers of poor prognosis. Explanations for the involvement of TTL and detyrosinated tubulin in tumor progression arise from the recent discovery that tubulin detyrosination leads to CAP-Gly protein mislocalization, which correlates with defects in spindle positioning during mitosis. Impaired control of spindle positioning is one factor favoring tumor invasiveness. Thus, TCP could be a target for developing novel therapeutic strategies against advanced stages of cancers. Inhibitors of TCP, by reversing abnormal detyrosinated tubulin accumulation in tumor cells, could impair tumor progression. TCP has never been isolated and this has hampered search of specific inhibitors. In this article, we describe a cell-based assay of TCP activity and its use to screen a library of natural extracts for their inhibitory potency. This led to the isolation of two sesquiterpene lactones. We subsequently found that parthenolide, a structurally related compound, can efficiently inhibit TCP. This inhibitory activity is a new specific property of parthenolide independent of its action on the nuclear factor-κB pathway. Parthenolide is also known for its anticancer properties. Thus, TCP inhibition could be one of the underlying mechanisms of these anticancer properties. [Cancer Res 2007;67(7):3371–8]
Low Incidence of Painless Thyroiditis in the Philadelphia Area
Authors: ALAN B. SCHORR, JEFFREY L. MILLER, PHILIP SHTASEL, LESLIE I. ROSE
Journal: Clinical Nuclear Medicine (1986)

Publications from the midwestern region of the United States have demonstrated an incidence of 14-23% of painless thyroiditis in hyperthyroid individuals. This possibly could represent a local phenomenon, and perhaps is not typical for other areas of the country. The 24 hour radioactive iodine uptakes in 152 consecutive hyperthyroid individuals in the Philadelphia area were evaluated. No patient in the series, with clinical and biochemical evidence of hyperthyroidism, had painless thyroiditis. It is concluded that the incidence of painless thyroiditis is markedly lower in the Philadelphia area than in the Midwest regions of the United States.
FURTHER POINTS ON THE STERILITY OF WOMEN
Authors: EDWARD REYNOLDS
Journal: JAMA (1913)

The treatment of sterility has long been one of the comparative failures of gynecology; and one of the most striking points of the case as I have seen them in practice has been the frequency with which women who have been in fact sterile to husbands who are known to have normal spermatozoa have, nevertheless, been pronounced normal even by practitioners of recognized authority. I have, moreover, seen this repeatedly, even when in my opinion a fully adequate cause for sterility was at once apparent in the genitals and when treatment of this condition resulted in prompt fertility. The frequent occurrence of such failures as these must evidently have a reason, which I believe to be that symptoms of ill health of sufficient degree to demand treatment are always dependent on the existence of gross pathologic conditions which we have all long been trained to perceive, but that sterility, on
Rank Signaling Links the Development of Invariant γδ T Cell Progenitors and Aire+ Medullary Epithelium
Authors: Natalie A. Roberts, Andrea J. White, William E. Jenkinson, Gleb Turchinovich, Kyoko Nakamura, David R. Withers, Fiona M. McConnell, Guillaume E. Desanti, Cecile Benezech, Sonia M. Parnell, Adam F. Cunningham, Magdalena Paolino, Josef M. Penninger, Anna Katharina Simon, Takeshi Nitta, Izumi Ohigashi, Yousuke Takahama, Jorge H. Caamano, Adrian C. Hayday, Peter J.L. Lane, Eric J. Jenkinson, Graham Anderson
Journal: Immunity (2012)

SummaryThe thymic medulla provides a specialized microenvironment for the negative selection of T cells, with the presence of autoimmune regulator (Aire)-expressing medullary thymic epithelial cells (mTECs) during the embryonic-neonatal period being both necessary and sufficient to establish long-lasting tolerance. Here we showed that emergence of the first cohorts of Aire+ mTECs at this key developmental stage, prior to αβ T cell repertoire selection, was jointly directed by Rankl+ lymphoid tissue inducer cells and invariant Vγ5+ dendritic epidermal T cell (DETC) progenitors that are the first thymocytes to express the products of gene rearrangement. In turn, generation of Aire+ mTECs then fostered Skint-1-dependent, but Aire-independent, DETC progenitor maturation and the emergence of an invariant DETC repertoire. Hence, our data attributed a functional importance to the temporal development of Vγ5+ γδ T cells during thymus medulla formation for αβ T cell tolerance induction and demonstrated a Rank-mediated reciprocal link between DETC and Aire+ mTEC maturation.Graphical abstractGraphical AbstractHighlights► Invariant Vγ5+ thymocytes regulate formation of Aire+ medullary thymic epithelium ► Generation of an invariant Vγ5+ T cell population requires thymus medulla development ► Skint-1-mediated Vγ5+ thymocyte development is Aire independent ► Dependency on Tnfrsf11a links γδ T cell and medullary epithelium development
PUMA Overexpression Induces Reactive Oxygen Species Generation and Proteasome-Mediated Stathmin Degradation in Colorectal Cancer Cells
Authors: Zhihe Liu, Huimei Lu, Honglian Shi, Yuchun Du, Jian Yu, Sheng Gu, Xian Chen, Ke Jian Liu, Chien-an A. Hu
Journal: Cancer Research (2005)

Increased amounts of reactive oxygen species (ROS) induce apoptosis in mammalian cells. PUMA (P53 up-regulated modulator of apoptosis), a mitochondrial proapoptotic BH3-only protein, induces rapid apoptosis through a Bax- and mitochondria-dependent pathway. However, the molecular basis of PUMA-induced apoptosis is largely not understood. Using a combination of biophysical and biochemical methods and PUMA-inducible colorectal cells, DLD-1.PUMA, we showed that (a) PUMA-induced apoptosis is dose and time dependent; (b) PUMA-induced apoptosis is directly associated with ROS generation; (c) diphenyleneiodonium chloride, a ROS blocker, or BAX-inhibiting peptide, a suppressor of BAX translocation, decreased ROS generation and apoptosis in DLD-1.PUMA cells; (d) overexpression of PUMA induced up-regulation (>1.34-fold) of peroxiredoxin 1 and down-regulation (by 25%) of stathmin through proteasome-mediated degradation; and (e) hydrogen peroxide down-regulated stathmin and disrupted the cellular microtubule network. Our findings indicate that PUMA induces apoptosis, in part, through the BAX-dependent generation of superoxide and hydrogen peroxide. ROS overproduction and oxidative stress induce proteome-wise alterations, such as stathmin degradation and disorganization of the cell microtubule network, in apoptotic cells.
Ethnic difference in the prevalence of systemic lupus erythematosus.
Authors: H H Hart, R R Grigor, D E Caughey
Journal: Annals of the Rheumatic Diseases (1983)

A retrospective study of systemic lupus erythematosus (SLE) was carried out in Auckland, New Zealand, for the years 1975 to 1980 inclusive. One hundred and fifty-one patients were found of which 106 fulfilled the American Rheumatism Association criteria. There were 15 deaths. Age-adjusted prevalence rates per 100 000 were estimated for all cases at the end of 1980 as follows: white 14.6, Polynesian 50.63, and other 19.11. There was a preponderance of females in each ethnic group, average 87% of all cases. Age-adjustment mortality rates per million patient years were: white 2.5 and Polynesians 13.0. Survival curves for both ethnic groups were similar. The prevalence rate in New Zealand Polynesian is significantly higher than in white counterparts which confirms the observation that the disease is commoner in the pigmented races.