tbuckley/cabot-search huggingface dataset:
Effects of High Altitude on the Eyes
Authors: Hugh H. Hussey
Journal: JAMA (1975)

ABSTRACT The current issue of Archives of Ophthalmology publishes a trio of articles that deal with the effects of high altitude on the ocular system and brain. All three reports emphasize the prevalence of high-altitude retinal hemorrhages that disappear after return to low altitudes.Rennie and Morissey (93:395-400, 1975) had the opportunity to study the American expedition to Dhaulagiri (8,167 meters [26,795 ft]), a mountain in the Central Himalayas, the sixth highest mountain in the world and the highest ever climbed without the use of supplemental oxygen.The expedition included 15 experienced American climbers, all of whom were physically fit, and five Nepali Sherpas. Retinal photographs had been taken at sea level before the start of the climb and were repeated at high altitude after the climbers had undertaken quite strenuous exertion. All of the American climbers manifested ocular changes including vascular engorgement and tortuosity, plus retinal hemorrhages in five instances.
Abstract 742: Up-regulation of histone deacetylases in colon cancer.
Authors: Hui Yang, Tal Salz, Maria Zajac-kaye, Daiqing Liao, Suming Huang, Yi Qiu
Journal: Cancer Research (2013)

Abstract The reversible acetylation of histones and non-histone proteins by histone acetyltransferases (HATs) and deacetylases (HDACs) play critical roles in transcriptional regulation in eukaryotic cells. Acetylation of histones is commonly associated with transcriptional activation of genes, and is thought to be responsible for the formation of a local “open chromatin” structure. In contrast, removal of acetyl groups by histone deacetylases (HDACs) frequently accompanies suppression of gene activity. Mammalian HDACs are classified into four classes (I, II, III and IV) based on the sequence homology to the yeast histone deacetylases Rpd3 (reduced potassium dependency), Hda1 (histone deacetylase1), and Sir2 (silent information regulator 2), respectively. Although the precise cellular functions of the different HDAC enzymes are still poorly understood, evidence suggests that different members of the HDAC family have distinct functions. It had been shown that overexpression of class I HDACs are more relevant to cancer development in many cancer types. In the absence of class I HDACs, cancer cells arrest either at the G1 phase of the cell cycle or the G2/M transition, resulting in the loss of mitotic cells, cell growth inhibition, and an increase in the percentage of apoptotic cells. Therefore, HDAC inhibitors had been used as a class of chemotherapeutic agents in cancer treatment. However, little is known about factors involved in regulation of class I expression in cancer cells. Our study focuses on the regulation of HDAC1 and 2 expressions in colon cancer cells. We found that compared with normal colon cell lines, both mRNA and protein level of HDAC1 and HDAC2 are higher in colon cancer cells, which suggests that HDAC1/2 is regulated at transcriptional level in colon cancer. HDAC1 and HDAC2 promoters were cloned and the promoter reporter activity was studied. Our result shows that HDAC1 and 2 promoters are highly active in colon cancer cells. Through mutation study on various putative transcription factors binding sites, we found that promoter activity is regulated by transcription factor Sp1/Sp3, which are also elevated in colon cancer cells lines and tissues. Chromatin immunoprecipitation assay also indicate that Sp1/Sp3 is recruited to HDAC1/HDAC2 promoter. Inhibition of Sp1/Sp3 through inhibitor or shRNA decreased HDAC1/2 expression and reduced cell proliferation. These results indicate that Sp1/Sp3 may be major regulators for HDAC1 and HDAC2 overexpression in colon cancer and this finding may shed light on future treatment of colon cancer. Citation Format: Hui Yang, Tal Salz, Maria Zajac-kaye, Daiqing Liao, Suming Huang, Yi Qiu. Up-regulation of histone deacetylases in colon cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 742. doi:10.1158/1538-7445.AM2013-742
Antibodies targeting the catalytic zinc complex of activated matrix metalloproteinases show therapeutic potential
Authors: Netta Sela-Passwell, Raghavendra Kikkeri, Orly Dym, Haim Rozenberg, Raanan Margalit, Rina Arad-Yellin, Miriam Eisenstein, Ori Brenner, Tsipi Shoham, Tamar Danon, Abraham Shanzer, Irit Sagi
Journal: Nature Medicine (2011)
HERNIA THROUGH THE FORAMEN OF WINSLOW
Authors: John Douglas
Journal: JAMA (1924)

In a recent article giving a careful review of the literature on the subject, Ullman<sup>1</sup>states that only thirty reports of cases of intestinal hernia through the foramen of Winslow can be found in which the diagnosis has been verified either by operation or by necropsy. Of these, only two are reported in the American literature, his own case and one by Engstad.<sup>2</sup>The case reported here is therefore considered of sufficient interest to place on record. <h3>REPORT OF CASE</h3><h3>History.</h3> —M. L. K., a woman, aged 76, admitted to St. Luke's Hospital, June 16, 1919, for five days before admission had suffered from general abdominal cramps, but had had no nausea or temperature elevation. The bowels had moved up to forty-eight hours before the time she entered the hospital, and during the twenty-four hours before admission she had vomited frequently. The only statements of any possible relevance
GSK is sued in US over alleged link of paroxetine to birth defects
Authors: J. H. Tanne
Journal: BMJ (2009)

GlaxoSmithKline (GSK) is facing the first of about 600 US lawsuits claiming that its antidepressant paroxetine (marketed as Paxil in the United States and Seroxat in the United Kingdom) caused birth defects in infants born to mothers who took the drug while pregnant. The first case has gone to jury in Philadelphia, Pennsylvania, where the company has locations in the city and its suburbs. The outcome of early trials often sets the trend for later cases.

In the Philadelphia case Michelle David claims that the drug caused life threatening heart defects in her son Lyam Kilker, who has had heart surgery several times. He is now almost 4 years old.

Lyam’s lawyer alleged in court that documents disclosed in the proceedings suggested that GSK had been aware in 1980 that information from rat studies indicated that paroxetine “could be” a cause of birth defects but that the company had decided to ignore them, reported Bloomberg, the financial news service (www.bloomberg.com, 15 Sep, “Glaxo executive’s memo suggested burying drug studies”).

A 1998 internal review by GSK of all reports of side effects tied paroxetine to an “alarmingly high number” of reports of birth defects, but the review report was not forwarded to the US Food and Drug Administration, the lawyer also alleged. It was not until 2003, when the …
CELLULAR RESISTANCE TO INFECTION
Authors: G. B. Mackaness
Journal: The Journal of Experimental Medicine (1962)

The mouse was found to be natively susceptible to Listeria monocytogenes. Its susceptibility was attributed to the capacity of the organism to survive and multiplying in host macrophages. During the first 3 days of a primary infection the bacterial populations of spleen and liver were found to increase at a constant rate. On the 4th day of infection the host became hypersensitive to Listeria antigens and at the same time bacterial growth ceased. A rapid inactivation of the organism ensued. Convalescent mice were resistant to challenge, but no protective factor could be found in their serum. Histological evidence suggested that acquired resistance was the result of a change occurring in the host's mononuclear phagocytes. When challenged in vitro, the macrophages of convalescent mice were found to resist infection with Listeria monocytogenes. Listeria-resistant cells appeared during the course of infection at a time which corresponded with the development of the antibacterial mechanism in the spleen. They persisted for as long as the antibacterial mechanism remained intact in this organ. This period of absolute resistance to Listeria lasted about 3 weeks. Thereafter, the host remained hypersensitive but unable to inactivate a challenge inoculum of Listeria. However, it remained capable of producing an accelerated response to reinfection. This was thought to depend upon an ability to generate a new population of resistant cells from a residuum of specifically sensitized macrophages or macrophage precursors still surviving in the tissues as a result of the immunological activation which occurred during the primary infection.
Estimates of survival from incurable prostate cancer need to be revised upwards
Authors: Z. Kmietowicz
Journal: BMJ (2013)

Men with advanced prostate cancer are living for an average of two years longer than they did a decade ago, an analysis has found.

The researchers said that the findings meant that the models used to predict survival among men with metastatic, castration resistant prostate cancer needed to be updated upwards to reflect the impact of new treatments.

The study looked at 442 men …
Diminished post-rest potentiation of contractile force in human dilated cardiomyopathy. Functional evidence for alterations in intracellular Ca2+ handling.
Authors: B Pieske, M Sütterlin, S Schmidt-Schweda, K Minami, M Meyer, M Olschewski, C Holubarsch, H Just, G Hasenfuss
Journal: Journal of Clinical Investigation (1996)

Post-rest contractile behavior of isolated myocardium indicates the capacity of the sarcoplasmic reticulum (SR) to store and release Ca2+. We investigated post-rest behavior in isolated muscle strips from nonfailing (NF) and endstage failing (dilated cardiomyopathy [DCM]) human hearts. At a basal stimulation frequency of 1 Hz, contractile parameters of the first twitch after increasing rest intervals (2-240 s) were evaluated. In NF (n = 9), steady state twitch tension was 13.7 +/- 1.8 mN/mm2. With increasing rest intervals, post-rest twitch tension continuously increased to maximally 29.9 +/- 4.1 mN/mm2 after 120s (P < 0.05) and to 26.7 +/- 4.5 mN after 240 s rest. In DCM (n = 22), basal twitch tension was 10.0 +/- 1.5 mN/mm2 and increased to maximally 13.6 +/- 2.2 mN/mm2 after 20 s rest (P < 0.05). With longer rest intervals, however, post-rest twitch tension continuously declined (rest decay) to 4.7 +/- 1.0 mN/mm2 at 240 s (P < 0.05). The rest-dependent changes in twitch tension were associated with parallel changes in intracellular Ca2- transients in NF and DCM (aequorin method). The relation between rest-induced changes in twitch tension and aequorin light emission was similar in NF and DCM, indicating preserved Ca(2-)-responsiveness of the myofilaments. Ryanodine (1 microM) completely abolished post-rest potentiation. Increasing basal stimulation frequency (2 Hz) augmented post-rest potentiation, but did not prevent rest decay after longer rest intervals in DCM. The altered post-rest behavior in failing human myocardium indicates disturbed intracellular Ca2- handling involving altered function of the SR.
Mercury Exposure in Young Adulthood and Incidence of Diabetes Later in Life
Authors: Ka He, Pengcheng Xun, Kiang Liu, Steve Morris, Jared Reis, Eliseo Guallar
Journal: Diabetes Care (2013)

Laboratory studies suggest that exposure to methylmercury at a level similar to those found in fish may induce pancreatic islet β-cell dysfunction. Few, if any, human studies have examined the association between mercury exposure and diabetes incidence. We examined whether toenail mercury levels are associated with incidence of diabetes in a large prospective cohort. RESEACH DESIGN AND METHODS: A prospective cohort of 3,875 American young adults, aged 20-32 years, free of diabetes in 1987 (baseline), were enrolled and followed six times until 2005. Baseline toenail mercury levels were measured with instrumental neutron-activation analysis. Incident diabetes was identified by plasma glucose levels, oral glucose tolerance tests, hemoglobin A1C levels, and/or antidiabetes medications.A total of 288 incident cases of diabetes occurred over 18 years of follow-up. In multivariate analyses adjusted for age, sex, ethnicity, study center, education, smoking status, alcohol consumption, physical activity, family history of diabetes, intakes of long-chain n-3 fatty acids and magnesium, and toenail selenium, toenail mercury levels were positively associated with the incidence of diabetes. The hazard ratio (95% CI) of incident diabetes compared the highest to the lowest quintiles of mercury exposure was 1.65 (1.07-2.56; P for trend = 0.02). Higher mercury exposure at baseline was also significantly associated with decreased homeostasis model assessment of β-cell function index (P for trend < 0.01).Our results are consistent with findings from laboratory studies and provide longitudinal human data suggesting that people with high mercury exposure in young adulthood may have elevated risk of diabetes later in life.
Calcification in The Aortic Arch of a Young Man
Authors: Jack E. Meyer
Journal: JAMA (1970)

Dr. Karl T. Benedict: The patient is a 24-year-old man who was admitted to the hospital for evaluation of abnormalities observed on a routine roentgenographic examination of the chest (Fig 1). Medical history included injuries to the skull and extremities in an automobile accident seven years prior to admission. The patient recovered uneventfully from these injuries. The remainder of the history, results of physical examination, and findings of routine laboratory studies were normal. <h3>Discussion</h3> Dr. Laurence L. Robbins: Dr. Hanelin, would you discuss this case? Dr. Joseph Hanelin: The significant finding is abnormal calcification in the slightly dilated aortic arch. The remainder of the chest appears normal, although I am somewhat concerned with the descending aorta; it seems slightly dilated. Dr. Robbins: Do you see any rib notching? Dr. Hanelin: There is no rib notching, and the heart size is normal. Was there a murmur? Dr. Benedict: There was no
Possible role of P-450 metabolite of arachidonic acid in vasodilator mechanism of angiotensin II type 2 receptor in the isolated microperfused rabbit afferent arteriole.
Authors: S Arima, Y Endo, H Yaoita, K Omata, S Ogawa, K Tsunoda, M Abe, K Takeuchi, K Abe, S Ito
Journal: Journal of Clinical Investigation (1997)

Although angiotensin II type 2 (AT2) receptor has recently been cloned, its functional role is not well understood. We tested the hypothesis that selective activation of AT2 receptor causes vasodilation in the preglomerular afferent arteriole (Af-Art), a vascular segment that accounts for most of the preglomerular resistance. We microperfused rabbit Af-Arts at 60 mmHg in vitro, and examined the effect of angiotensin II (Ang II; 10(-11)-10(-8) M) on the luminal diameter in the presence or absence of the Ang II type 1 receptor antagonist CV11974 (CV; 10(-8) M). Ang II was added to both the bath and lumen of preconstricted Af-Arts. Ang II further constricted Af-Arts without CV (by 74+/-7% over the preconstricted level at 10(-8) M; P < 0.01, n = 7). In contrast, in the presence of CV, Ang II caused dose-dependent dilation; Ang II at 10(-8) M increased the diameter by 29+/-2% (n = 7, P < 0.01). This dilation was completely abolished by pretreatment with an AT2 receptor antagonist PD123319 (10(-7) M, n = 6), suggesting that activation of AT2 receptor causes vasodilation in Af-Arts. The dilation was unaffected by inhibiting either nitric oxide synthase (n = 7) or cyclooxygenase (n = 7), however, it was abolished by either disrupting the endothelium (n = 10) or inhibiting the cytochrome P-450 pathway, particularly the synthesis of epoxyeicosatrienoic acids (EETs, n = 7). These results suggest that in the Af-Art activation of the AT2 receptor may cause endothelium-dependent vasodilation via a cytochrome P-450 pathway, possibly by EETs.
Idiopathic hypercalciuria and hyperparathyroidism.
Authors: D R Davies, C E Dent, L Watson
Journal: BMJ (1971)

nisms isolated from the pregnant patients when compared with women with acute "cystitis," both groups coming from the same geographical area.6It cannot, therefore, be valid to make the comparison in your editorial as support for geographical variation in sulphonamide resistance.-Weare, etc.,
On Borrowed Time: Observations on Children with Implanted Cardiac Pacemakers and Their Families
Authors: RICHARD GALDSTON, WALTER J. GAMBLE
Journal: American Journal of Psychiatry (1969)

A seven-year study of 16 children and two adults with implanted pacemakers showed that the patients and their parents were singularly free from evidence of regression in psychic functioning. Their accommodation to the stress of heart block and artificial pacing was achieved through a triad of psychological processes: identification with a medical attitude, intellectualization, and denial of affect.
Cranial Nerve Syndromes Relation to Exogenous And Endogenous Substances
Authors: Michael Scott
Journal: JAMA (1968)

<h3>To the Editor:—</h3> The apparent sensitivity of some cranial nerves to ingested or injected substances is a unique vulnerability, not generally appreciated. A careful study might reveal the cause of some cranial nerve syndromes of unknown etiology such as tic douloureux, Bell's palsy, facial hemispasm, certain types of deafness, tinnitus, vertigo, glossopharyngeal neuralgia, and spasmodic torticollis. The first (olfactory) nerve is susceptible to nasal or viral infections which can cause transitory and occasionally permanent loss of smell. The second nerve (optic) is sensitive to methanol, optochin, cortisone and cortisone-like substances, tobacco (nicotine), quinine, ethylene glycol (Prestone), aspidium, and other substances. The third, fourth, and sixth cranial nerves (oculomotor, trochlear, and abducens) are often involved in diabetes and syphilis. They are occasionally affected following spinal anesthesia. The trigeminal nerve (fifth) is involved in tic douloureux, a syndrome of unknown etiology. This nerve is affected by stilbamidine, diphenylhydantoin sodium, trichloroethylene, and carbamazepine
Latent Hypoparathyroidism in Children With Conotruncal Cardiac Defects
Authors: Bettina F. Cuneo, Craig B. Langman, Michel N. Ilbawi, V. Ramakrishnan, Anthony Cutilletta, Deborah A. Driscoll
Journal: Circulation (1996)

Background DiGeorge anomaly is characterized by hypoplasia or atresia of the thymus and parathyroid glands resulting in T cell–mediated immune deficiency, hypocalcemic hypoparathyroidism, and conotruncal cardiac defects. It usually is associated with deletions of chromosomal region 22q11. We hypothesized that the stimulated (secretory reserve) but not the constitutive secretion of parathyroid hormone would be reduced in normocalcemic children with conotruncal cardiac defects but no overt immune deficiency and would be related to the presence of a deletion in the DiGeorge chromosomal region of 22q11. Methods and Results Blood-ionized calcium and serum-intact parathyroid hormone were measured at baseline and seven more times during hypocalcemia induced during cardiopulmonary bypass in 22 patients and 10 control subjects with an atrial septal defect. Chromosomal deletions were detected by fluorescent in situ hybridization and DNA dosage analysis. There were no differences in basal calcium and parathyroid hormone levels between patients and control subjects. All had increased parathyroid hormone in response to hypocalcemia; despite lower calcium levels, parathyroid hormone levels were lower in patients. The parathyroid hormone secretory reserve in 14 of 22 patients was reduced compared with control subjects; 4 of the 14 had deletions. Conclusions A significant number of children with conotruncal cardiac defects have normocalcemia and a normal constitutive level of parathyroid hormone but deficient parathyroid hormone secretory reserve; about 30% also have 22q11 deletions. Such children may be at risk for the later development of hypocalcemic hypoparathyroidism.
Ethics and SARS: lessons from Toronto
Authors: P. A Singer
Journal: BMJ (2003)

The SARS epidemic showed how easy it is for infectious diseases to spread round the world. Ethical as well as clinical issues need to be resolved to improve the response to the next epidemic 

The outbreak of severe acute respiratory syndrome (SARS) in the Toronto area earlier this year forced medical and government workers to make hard choices, often with limited information and short deadlines. Healthcare providers were on the firing line, and were the people most affected by the disease.1 Decision makers had to balance individual freedoms against the common good, fear for personal safety against the duty to treat sick people, and economic losses against the need to contain the spread of a deadly disease. Such decisions have to be guided by both scientific knowledge and ethical considerations. The SARS outbreak showed that Canadian society was not fully prepared to deal with the ethical issues.

We formed a working group to identify the key ethical issues and values most important for an analysis of ethical dimensions of the SARS epidemic. The final list of issues and values was agreed by a consensus process and found to have face validity and credibility. We then developed a framework for looking at the ethical implications of the SARS outbreak, identifying 10 key ethical values relevant to SARS (box), and five major ethical issues faced by decision makers.

We examined the underlying ethical values for the five major issues and drew lessons from how each was tackled. The following case studies illustrate the issues and are an amalgam of our experiences.

A medical clerk is asked by public health officials to remain at home in quarantine for 10 days because of possible exposure to SARS. She wants to comply but fears this could cost both her job and her apartment. 

Five …
Vasectomy and increased risk of prostate cancer
Authors: R. L. Levine
Journal: JAMA (1993)

To the Editor.  —Giovannucci et al 1 failed to consider the most important variable associated with diagnosing prostate cancer in the United States, that is, a patient-urologist encounter. In another study linking vasectomy to prostate cancer, Rosenberg et al 2 failed to address the same issue. Although participants in both studies provided detailed information on various lifestyle variables, information on contact with urologists was lacking. Giovannucci et al addressed detection bias by confirming that the frequency of rectal examination was similarly high in men with and without vasectomy. Rosenberg et al questioned whether vasectomized men were more health conscious and more likely to undergo surveillance than nonvasectomized men but dismissed the possibility since the risk of prostate cancer was still increased 15 years after vasectomy, when they felt it would be unlikely that men were still undergoing regular rectal examination related to vasectomy.  Men electing vasectomy may have in common