tbuckley/cabot-search huggingface dataset:
Up-regulation of GPR48 Induced by Down-regulation of p27<i>Kip1</i> Enhances Carcinoma Cell Invasiveness and Metastasis
Authors: Yun Gao, Kyoko Kitagawa, Yoshihiro Hiramatsu, Hirotoshi Kikuchi, Tomoyasu Isobe, Mai Shimada, Chiharu Uchida, Takayuki Hattori, Toshiaki Oda, Keiko Nakayama, Keiichi I. Nakayama, Tatsuo Tanaka, Hiroyuki Konno, Masatoshi Kitagawa
Journal: Cancer Research (2006)

Abstract A reduced expression level of the cyclin-dependent kinase inhibitor p27Kip1 is associated with increased tumor malignancy and poor prognosis in individuals with various types of cancer. To investigate the basis for this relation, we applied microarray analysis to screen for genes differentially expressed between p27+/− and parental (p27+/+) HCT116 human colon carcinoma cells. Expression of the gene for G protein–coupled receptor 48 (GPR48) was increased in the p27+/− cells. Forced expression of GPR48 increased both in vitro invasive activity and lung metastasis potency of HCT116 cells. In contrast, depletion of endogenous GPR48 by RNA interference reduced the invasive potential of HeLa and Lewis lung carcinoma cells not only in vitro but also in vivo. Moreover, GPR48 expression was significantly associated with lymph node metastasis and inversely correlated with p27 expression in human colon carcinomas. GPR48 may thus play an important role in invasiveness and metastasis of carcinoma and might therefore represent a potential prognostic marker or therapeutic target. (Cancer Res 2006; 66(24): 11623-31)
Aberrant expression and biological significance of Sox2, an embryonic stem cell transcriptional factor, in ALK-positive anaplastic large cell lymphoma
Authors: P Gelebart, S A Hegazy, P Wang, K M Bone, M Anand, D Sharon, M Hitt, J D Pearson, R J Ingham, Y Ma, R Lai
Journal: Blood Cancer Journal (2012)

Sox2 (sex-determining region Y-Box) is one of the master transcriptional factors that are important in maintaining the pluripotency of embryonic stem cells (ESCs). In line with this function, Sox2 expression is largely restricted to ESCs and somatic stem cells. We report that Sox2 is expressed in cell lines and tumor samples derived from ALK-positive anaplastic large cell lymphoma (ALK(+)ALCL), for which the normal cellular counterpart is believed to be mature T-cells. The expression of Sox2 in ALK(+)ALCL can be attributed to nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), the oncogenic fusion protein carrying a central pathogenetic role in these tumors. By confocal microscopy, Sox2 protein was detectable in virtually all cells in ALK(+)ALCL cell lines. However, the transcriptional activity of Sox2, as assessed using a Sox2-responsive reporter construct, was detectable only in a small proportion of cells. Importantly, downregulation of Sox2 using short interfering RNA in isolated Sox2(active) cells, but not Sox2(inactive) cells, resulted in a significant decrease in cell growth, invasiveness and tumorigenicity. To conclude, ALK(+)ALCL represents the first example of a hematologic malignancy that aberrantly expresses Sox2, which represents a novel mechanism by which NPM-ALK mediates tumorigenesis. We also found that the transcriptional activity and oncogenic effects of Sox2 can be heterogeneous in cancer cells.
A placebo-controlled randomized study on the clinical effectiveness, immunohistochemical changes and protoporphyrin IX accumulation in fractionated 5-aminolaevulinic acid-photodynamic therapy in patients with psoriasis
Authors: T. Smits, M.M. Kleinpenning, P.E.J. Van Erp, P.C.M. Van De Kerkhof, M-J.P. Gerritsen
Journal: British Journal of Dermatology (2006)

Topical 5-aminolaevulinic acid (ALA)-photodynamic therapy (PDT) for the treatment of psoriasis has been evaluated in a few studies. In these studies different treatment parameters were used, there was a variable clinical response, and a nonhomogeneous fluorescence was seen after irradiation with Wood's light.To study the clinical effectiveness, immunohistochemical changes and protoporphyrin IX accumulation in ALA-PDT in patients with psoriasis. Eight patients with stable plaque psoriasis with symmetrical involvement were included in the study. Two symmetrical plaques were randomly allocated to PDT either with 10% ALA or with placebo. Irradiation consisted of 2 and 8 J cm(-2) with a dark interval of 2 h (Waldmann PDT 1200 L, 600-750 nm, 40 mW cm(-2)) once weekly for 4 weeks. Before, during and after irradiation, fluorescence diagnosis was performed. Biopsies were taken at baseline, week 1 and week 6 for immunohistochemical assessment. Psoriatic plaques were clinically assessed using the plaque severity (sum) score. Fluorescence diagnosis was performed and expression of immunohistochemical markers for proliferation, differentiation and T-cell infiltration [Ki67, keratin 10 (K10), CD4, CD8 and CD45RO] was assessed.From week 1 up to week 6, ALA-PDT gave a significant reduction in the number of Ki67+ nuclei, while the K10 expression increased. After 6 weeks significant improvement was observed for CD8 and CD45RO. These changes were absent in the placebo-treated lesions. The sum scores were also significantly lower in the ALA-treated plaques. Heterogeneity of macroscopic fluorescence was observed during treatment despite keratolytic treatment.The present study shows that clinical improvement during fractionated ALA-PDT in psoriasis parallels histological improvement as seen in normalization of epidermal proliferation, differentiation and infiltration of relevant T-cell subsets. Optimizing the current treatment protocol may increase clinical efficacy further.
THE COLLOQUIUM ON BIOMEDICAL MORES
Authors: G. E. W. WOLSTENHOLME
Journal: Annals of Internal Medicine (1968)

Letters and Comments1 February 1968THE COLLOQUIUM ON BIOMEDICAL MORESG. E. W. WOLSTENHOLME, OBE., F.R.C.P., FIBIOL.G. E. W. WOLSTENHOLME, OBE., F.R.C.P., FIBIOL.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-2-492 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: It was very thoughtful and kind of you to send me copies of the September edition of ANNALS OF INTERNAL MEDICINE and the Supplement 7 (entitled: "The Changing Mores of Biomedical Research"). I am most interested to see the discussion that was held during the 48th Annual Session of the American College of Physicians in San Francisco, which will be particularly useful to me in talking in the future to medical students and others about these problems.I find it very encouraging that there is such an active response to the unprecedented questions that are posed by... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Ciba Foundation 41 Portland Place London, W. 1. England PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1968Volume 68, Issue 2Page: 492-493KeywordsForecasting Issue Published: 1 February 1968 PDF DownloadLoading ...
Unidentified Body of a Child
Authors: Clyde C. Snow
Journal: JAMA (1976)

To the Editor.—  On Sept 7, 1975, a child's body was found in a plastic bag near Giddings, Tex. Examination revealed the following: Time of death, summer 1975; age at death, 4±1 years; race, caucasoid; sex, female (?); hair, very dark brown, straight, about 10 cm long; cause of death, undetermined.  Three well-healed burr holes indicate that this child underwent neurosurgery at least several months before death. Two of the holes straddle the coronal suture bilaterally about 3.5 cm from the midline; third is located in the left parietal, just posterior to the coronal suture, about 7.5 cm from midline. The central (left frontoparietal) hole is the largest, measuring 15×20 mm in diameter. The other two are approximately 5×10 mm in diameter.  The left anterior frontal bone displays extensive patches of healed periostitis both endocranially and ectocranially. Externally, the periostitis extends downward to involve the nasal bones, maxilla and mandible. These
Myocardial enzyme depletion in infarcted human hearts: infarct size and equivalent tissue mass
Authors: F. H van der VEEN, R. VISSER, G. M WILLEMS, B. KOP-KLAASSEN, W. T. HERMENS
Journal: Cardiovascular Research (1988)

Myocardial activities of several enzymes were measured in infarcted and non-infarcted areas of heart sections obtained from eight patients who died after acute myocardial infarction. Similar data were obtained from four patients with cardiovascular disorders who died from causes other than myocardial infarction and from six patients without previously known heart disease. It was found that both non-infarcted and infarcted tissue samples contained considerably altered enzyme activities. This finding explains the low correlations between enzymatic and histological estimates of infarct size previously reported. However, when the residual myocardial activities of different enzymes were compared with each other, a close correlation was found between creatine kinase, alpha-hydroxybutyrate dehydrogenase, and aspartate aminotransferase. It appears that the pathological changes in the myocardial activities of these enzymes may be explained by the phenomenon of diluted myocardium. This indicates that myocardial injury, as estimated from plasma enzyme activities, may still be expressed meaningfully in gram equivalents of healthy myocardium.
Factors Affecting the Association of Oral Contraceptives and Ovarian Cancer
Authors: Daniel W. Cramer, George B. Hutchison, William R. Welch, Robert E. Scully, Robert C. Knapp
Journal: New England Journal of Medicine (1982)

We investigated the relation between epithelial ovarian cancer and the use of oral contraceptives in a case–control study of 144 white women under the age of 60 who had ovarian cancer and 139 white women under 60 who were selected from the general population. We observed a decreased risk for ovarian cancer associated with the use of oral contraceptives in subjects 40 through 59 years of age at the time of the study. The relative risk, adjusted for parity, was 0.11, with 95 per cent confidence limits of 0.04 to 0.33. In contrast to the findings in older women, a decreased risk for ovarian cancer associated with oral-contraceptive use was not found in women under 40. In this group, the adjusted relative risk associated with any use of oral contraceptives was 1.98, with 95 per cent confidence limits of 0.74 to 5.27. The lowest risk for ovarian cancer associated with the use of oral contraceptives was observed in older parous subjects and in women who had discontinued use more than 10 years previously. (N Engl J Med. 1982; 307:1047–51.)
Back to the whale bone?
Authors: A J P M SMOUT
Journal: Gut (1999)

See article on page 231 

Most doctors with any practical experience of achalasia would be willing to admit that the disorder often provides considerable professional satisfaction. Firstly, it can be very satisfying to make the diagnosis. Far too often, patients will have suffered from gradually worsening dysphagia for many years and the diagnosis will have been missed at earlier consultations. The second moment of satisfaction can be enjoyed when the symptoms are relieved immediately after a relatively simple procedure such as pneumatic dilatation.

Malfunction of the lower oesophageal sphincter (LOS) plays a key role in the genesis of dysphagia in achalasia, in which it usually maintains an abnormally high resting tone. More importantly, however, the LOS does not relax sufficiently on swallowing, causing a persistent barrier to food boluses. In addition, the oesophageal body lacks normal propagation of contractions.

Presently there are four therapeutic options in achalasia, all of which are directed at lowering the tone of the LOS.

In what is considered to be the first report on treatment of achalasia, Sir Thomas Willis in 1672 described the successful dilatation of the sphincter using a …
Severe maternal sepsis should be considered obstetric emergency
Authors: J. Wise
Journal: BMJ (2014)

Signs of severe sepsis, particularly with confirmed or suspected group A streptococcal infection, should be considered an obstetric emergency and routinely included in obstetric emergency training courses, researchers have concluded.1

A study, published in the open access journal PLoS Medicine , found that for each maternal sepsis death in the UK, approximately 50 women have life threatening morbidity from sepsis.

Researchers, led by Marian Knight from the University of Oxford, say doctors should be aware that antibiotics do not necessarily …
Use of breath carbon monoxide measurements to assess erythrocyte survival in subjects with chronic diseases
Authors: Benjamin L. Mitlyng, Jasvinder A. Singh, Julie K. Furne, John Ruddy, Michael D. Levitt
Journal: American Journal of Hematology (2006)

Anemia is very common in patients with chronic diseases. To determine the role of increased red blood cell (RBC) turnover in such subjects, we estimated RBC survival in three groups of chronically ill patients using a simple technique in which RBC life span is estimated via measurements of breath carbon monoxide concentration. The study groups consisted of subjects with: (1) osteoarthritis, (2) rheumatoid arthritis, and (3) anemia who were hospitalized for treatment of a variety of chronic illnesses. None of the anemic subjects had evidence of hemorrhage, a deficiency state, or a marrow abnormality to account for their reduced hemoglobin concentration. Subjects with osteoarthritis had a mean RBC life span (127 ± 25 days) that did not differ significantly from normal (122 ± 23 days). In contrast, RBC life span was significantly reduced (P < 0.001) in both the rheumatoid arthritis subjects (90 ± 15 days) and the anemic, hospitalized patients (87 ± 33 days). The hemoglobin concentration of the rheumatoid patients was near normal (13.5 ± 1.5 g/dl), indicating that the marrow was compensating for the reduced RBC life span, whereas no such compensation was apparent in the anemic, chronically ill subjects. We conclude that a modest (approximately 25%) reduction in RBC life span commonly occurs in patients with chronic disease, and this reduction becomes clinically relevant in subjects whose marrow cannot respond with increased RBC output. Am. J. Hematol. 81:432–438, 2006. © 2006 Wiley-Liss, Inc.
Postmenopausal estrogen therapy selectively stimulates hepatic enlargement in women with autosomal dominant polycystic kidney disease
Authors: R Sherstha, C McKinley, P Russ, A Scherzinger, T Bronner, R Showalter, G T Everson
Journal: Hepatology (1997)

The goal of this study was to determine whether use of postmenopausal estrogen (Premarin ® , Wyeth-Ayerst, Philadelphia, PA) in women with autosomal dominant polycystic kidney disease (ADPKD) increases liver, hepatic cyst, or kidney volume. We also determined whether clinical symptoms correlated with the volume of either the liver or kidneys. Eight women off estrogen (control, C) and 11 others on estrogen (Premarin ® , E) were studied basally and after 1 year. The two groups were similar in age, weight, age at menarche, and gravida. Volumes of total liver, hepatic cysts, hepatic parenchyma, and total kidney were measured by a validated computed tomography (CT) technique. Estrogen treatment was associated with a selective increase in total liver volume (E vs. C: Δ = 7% ± 12% vs. -2% ± 8%, P &lt; .03) and no change in kidney volume (E vs. C: Δ = 0% ± 6% vs. -2% ± 6%, P = NS). Symptoms were common, regardless of estrogen treatment (abdominal pain 60%, shortness of breath 40%, or both 35%). Patients with symptoms of abdominal pain and shortness of breath had significantly increased hepatic volumes ( P &lt; .03) but similar kidney volume compared with patients without symptoms. We conclude that estrogen treatment of postmenopausal ADPKD women is associated with selective liver enlargement and that abdominal symptoms in ADPKD patients may be because of extensive hepatic cystic disease.
Risk of Developing Colorectal Cancer Following a Negative Colonoscopy Examination
Authors: Harminder Singh, Donna Turner, Lin Xue, Laura E. Targownik, Charles N. Bernstein
Journal: JAMA (2006)

Limited evidence exists to guide the optimal frequency of repeat endoscopic examination for colorectal cancer screening after a negative colonoscopy.To determine the duration and magnitude of the risk of developing colorectal cancer following performance of a negative colonoscopy.Population-based retrospective analysis of individuals whose colonoscopy evaluations did not result in a diagnosis of colorectal neoplasia. Patients who had been evaluated between April 1, 1989, and December 31, 2003, were identified using Manitoba Health's physician billing claims database (N = 35 975). Standardized incidence ratios (SIRs) were calculated to compare colorectal cancer incidence in our cohort with colorectal cancer incidence in the provincial population. Stratified analysis was performed to determine the duration of the reduced risk. Patients with a history of colorectal cancer prior to the index colonoscopy, inflammatory bowel disease, resective colorectal surgery, and lower gastrointestinal endoscopy within the 5 years before the index colonoscopy were excluded. Cohort members were followed up from the time of the index colonoscopy until diagnosis of colorectal cancer, death, out-migration from Manitoba, or end of the study period on December 31, 2003.Incidence of colorectal cancer.A negative colonoscopy was associated with SIRs of 0.69 (95% confidence interval [CI], 0.59-0.81) at 6 months, 0.66 (95% CI, 0.56-0.78) at 1 year, 0.59 (95% CI, 0.48-0.72) at 2 years, 0.55 (95% CI, 0.41-0.73) at 5 years, and 0.28 (95% CI, 0.09-0.65) at 10 years. The proportion of colorectal cancer located in the right side of the colon was significantly higher in the colonoscopy cohort than the rate in the Manitoba population (47% vs 28%; P<.001).The risk of developing colorectal cancer remains decreased for more than 10 years following the performance of a negative colonoscopy. There is a need to improve the early detection rate of right-sided colorectal neoplasia in usual clinical practice.
Ventricular Fluid and the Management of Coccidioidal Meningitis
Authors: Elliot Goldstein, M. J. Winship, Demosthenes Pappagianis
Journal: Annals of Internal Medicine (1972)

An Ommaya reservoir is often used to administer chemotherapy in the treatment of fungal meningitis. Since management of these chronic infections requires periodic analyses of cerebrospinal fluid, there is a tendency to obtain specimens from this site rather than from repeated lumbar taps. In three cases of meningitis due to Coccidioides immitis, one of which was complicated by a staphylococcal superinfection, analysis of ventricular fluid obtained from the reservoir was diagnostically misleading. This fluid usually showed protein concentrations of less than 30 mg/100 ml, glucose concentrations of more than 57 mg/100 ml, falsely low complement-fixing antibody titers, and small numbers of cells. Spinal fluid from the lumbar space showed the characteristic abnormalities associated with meningitis, in protein, glucose, and cellular constituents. This masking effect is caused by physiological differences between ventricular and lumbar fluid and can be great enough to limit the diagnostic value of ventricular fluid.
Prenatal methylmercury exposure and children: neurologic, developmental, and behavioral research.
Authors: G J Myers, P W Davidson
Journal: Environmental Health Perspectives (1998)

Mercury is present in the earth's crust and is methylated by bacteria in aquatic environments to methylmercury (MeHg). It is then concentrated by the food chain so predatory fish and sea mammals have the highest levels. Thus, consuming seafood leads to exposure. MeHg readily crosses the placenta and the blood-brain barrier and is neurotoxic. The developing fetal nervous system is especially sensitive to its effects. Prenatal poisoning with high dose MeHg causes mental retardation and cerebral palsy. Lower level exposures from maternal consumption of a fish diet have not been consistently associated with adverse neurodevelopmental outcomes. However, most studies have considerable uncertainty associated with their results. Two large controlled longitudinal studies of populations consuming seafood are underway that are likely to determine if any adverse effects can be identified. No adverse associations have been found in the Seychelles, where exposure is mainly from fish consumption. In the Faroe Islands where exposure is primarily from consumption of whale meat and not fish, adverse associations have been reported. The Seychelles population consumes large amounts of marine fish containing MeHg concentrations similar to commercial fish in the United States. Current evidence does not support the hypothesis that consumption of such fish during pregnancy places the fetus at increased neurodevelopmental risk.
When is movement controlled by the dorsal stream?
Authors: Gordon Binsted, Les G. Carlton
Journal: Behavioral and Brain Sciences (2002)

Our commentary focuses on the functional link between the ventral and dorsal systems implied by Norman, as they relate to overt movement. While issues relating to space perception and size constancy are the primary justification for this dual-process theory, the philosophical extensions of this approach are less consistent with examination of motor control and, in particular, motor learning.
Mortality and hormone-related exposures in women with diabetes.
Authors: B E Klein, R Klein, S E Moss
Journal: Diabetes Care (1999)

OBJECTIVE: Hormone-related events and exposures are related to mortality and especially to cardiovascular disease in women. We evaluated whether such exposures influenced risk in a well-defined group of women with diabetes. RESEARCH DESIGN AND METHODS: Women with younger- and older-onset diabetes who were identified during a population-based study were queried about number of pregnancies, age at menarche, use of oral contraceptives, use of estrogen replacement therapy, and menopausal status at examinations in 1984-1986. Analyses are limited to women aged &amp;gt; or = 18 years (n = 398 and 542 in those with younger- and older-onset diabetes, respectively). Cohort mortality was monitored carefully, and causes of death were abstracted from death certificates. RESULTS: There were 58 deaths in the first group and 338 deaths in the second group since the 1984-1986 examination. The number of pregnancies was significantly associated with all-cause mortality (hazard ratio, 0.96 [95% CI 0.92-1.00]) in older-onset women only. CONCLUSIONS: These data suggest and are compatible with the notion that the hormone exposures examined are unrelated to cardiovascular mortality in women with diabetes, with the exception of a minimal effect of the number of pregnancies in older-onset women. Whether there is a difference in these exposure-outcome relationships between women with diabetes and those without diabetes is uncertain and requires further investigation.
Surgical Treatment of Retrograde Jejunogastric Intussusception after Temporary Endoscopic Management
Authors: S. Guadagni, M. A. Pistoia, M. Catarci, F. Carboni, F. Pistoia, L. Lombardi, M. Carboni
Journal: Endoscopy (1991)

See also: Jejunogastric Intussusception, an Acute Exacerbation Diagnosed by GastroscopyEndoscopy 1981; 13(03): 131-133DOI: 10.1055/s-2007-1021666