tbuckley/cabot-search huggingface dataset:
Increased interleukin-1 and interleukin-6 serum concentrations in severe primary pulmonary hypertension.
Authors: M Humbert, G Monti, F Brenot, O Sitbon, A Portier, L Grangeot-Keros, P Duroux, P Galanaud, G Simonneau, D Emilie
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Primary pulmonary hypertension (PPH) is characterized by the proliferation of smooth-muscle cells, fibroblasts, and endothelial cells in the walls of small pulmonary arteries. In order to evaluate a role for proinflammatory cytokines in this process, we studied the concentration of interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF alpha) in the serum of 29 patients with severe PPH referred to our center for lung transplantation. Results were compared with those obtained in 15 normal controls and nine patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD-PH). TNF alpha serum levels were within the normal range in each group. This contrasted with increased IL-1 beta serum levels in severe PPH (118 +/- 36 pg/ml, mean +/- SEM) as compared with controls (3 +/- 1 pg/ml, p < 0.001) or COPD-PH patients (3 +/- 1 pg/ml, p < 0.001). IL-6 serum concentrations were also higher in severe PPH (66 +/- 20 pg/ml) than in controls (14 +/- 6 pg/ml, p < 0.01). This study demonstrates increased serum levels of IL-1 beta and IL-6 in severe PPH, and suggests a role for proinflammatory cytokines in PPH.
Type B<i>Haemophilus influenzae</i>Infections in Adults
Authors: Louis Weinstein
Journal: New England Journal of Medicine (1970)

The paper by Norden, Callerame and Baum in this issue of the Journal calls attention to a facet of Haemophilus influenzae infections that has aroused only sporadic interest in the past. Although this kind of disease has been known to occur in adults for many years, the few cases in this age group have stimulated the description of single ones and the association of its pathogenesis with either a local or a generalized defect in host defense mechanisms. Thus, many reports have emphasized the relation of susceptibility to this type of infection to deficient or defective immunoglobulins, antibiotic-therapy (superinfection), spinal . . .
Why do some ex-armed forces personnel end up in prison?
Authors: Deirdre MacManus, Simon Wessely
Journal: BMJ (2011)

New report emphasises the role of alcohol, social exclusion, and financial problems

On 23 June the well respected Howard League for Penal Reform published their report on ex-serving armed forces personnel in prison.1 The league’s remit was to find out why so many of these people become involved in the criminal justice system, to explore the problems facing them on transition back into civilian life, and to look at the reasons underlying their offending behaviour. It is hoped that the report can provide information on how these individuals’ needs can best be met both in prison and in the community. 

Concerns about how service personnel will reintegrate into society after war are nothing new. After the second world war, returning veterans were often seen less as heroes and more as potential social problems with violence and offending high on the list of concerns.2 Since 2001, more than 160 000 UK regular and reserve forces have been deployed in Iraq, Afghanistan, or both counties. There have been many accounts in the media of the challenges these individuals face in their transition back to civilian life, including problems related to housing, mental health, employment, relationship breakdown, and substance misuse,3 but also aggression, violent offending, and incarceration.4

Research examining the effects of war on psychological functioning has focused mainly on clinical outcomes, such …
Genomic Profiles Specific to Patient Ethnicity in Lung Adenocarcinoma
Authors: Philippe Broët, Cyril Dalmasso, Eng Huat Tan, Marco Alifano, Shenli Zhang, Jeanie Wu, Ming Hui Lee, Jean-François Régnard, Darren Lim, Heng Nung Koong, Thirugnanam Agasthian, Lance D. Miller, Elaine Lim, Sophie Camilleri-Broët, Patrick Tan
Journal: Clinical Cancer Research (2011)

East-Asian (EA) patients with non-small-cell lung cancer (NSCLC) are associated with a high proportion of nonsmoking women, epidermal growth factor receptor (EGFR)-activating somatic mutations, and clinical responses to tyrosine kinase inhibitors. We sought to identify novel molecular differences between NSCLCs from EA and Western European (WE) patients.A total of 226 lung adenocarcinoma samples from EA (n = 90) and WE (n = 136) patients were analyzed for copy number aberrations (CNA) by using a common high-resolution SNP (single nucleotide polymorphism) microarray platform. Univariate and multivariate analyses were carried out to identify CNAs specifically related to smoking history, EGFR mutation status, and ethnicity.The overall genomic profiles of adenocarcinomas from EA and WE patients were highly similar. Univariate analyses revealed several CNAs significantly associated with ethnicity, EGFR mutation, and smoking, but not to gender, and KRAS or p53 mutations. A multivariate model identified four ethnic-specific recurrent CNAs-significantly higher rates of copy number gain were observed on 16p13.13 and 16p13.11 in EA tumors, whereas higher rates of genomic loss on 19p13.3 and 19p13.11 were observed in tumors from WE patients. We identified several potential driver genes in these regions, showing a positive correlation between cis-localized copy number changes and transcriptomic changes.16p copy number gains (EA) and 19p losses (WE) are ethnic-specific chromosomal aberrations in lung adenocarcinoma. Patient ethnicity should be considered when evaluating future NSCLC therapies targeting genes located on these areas.
Prenatal Growth, BMI, and Risk of Type 2 Diabetes by Early Midlife
Authors: Elina Hyppönen, Chris Power, George Davey Smith
Journal: Diabetes Care (2003)

OBJECTIVE—Small size at birth has been associated with increased risk of type 2 diabetes. Our aim was to evaluate how risk of diabetes associated with low birth weight is affected by accumulation of body mass from childhood to adulthood. RESEARCH DESIGN AND METHODS—Subjects from the 1958 British birth cohort (born 3–9 March 1958) have been followed regularly since birth. In the survey at 41 years of age, 88 participants reported type 2 diabetes (n = 10,683). RESULTS—Participants in whom diabetes developed weighed less at birth and had higher BMIs than the others. Birth weight (adjusted for gestational age and sex) was inversely related to risk of diabetes (odds ratio for 1-SD change 0.76, 95% CI 0.56–0.99). All diabetic participants in the lowest third of birth weight were in the highest third of weight gain by 23 years of age. An increased risk of diabetes was found for those in the lowest third of BMI at 7 years of age (2.84, 1.2–6.9), but diabetic participants in this group had excessive weight gain to 23 years of age. All but one diabetic participant in the highest third of childhood BMI remained in the highest third until 23 years of age. Risk of diabetes by BMI at 23 years of age was 22.9-fold (95% CI 12–42) for obese participants and 3.8-fold (2.1–6.9) for overweight participants compared with those of normal weight. CONCLUSIONS—There was no increase in risk of diabetes for small size at birth without excessive postnatal weight gain. Adult obesity was the most important risk factor for type 2 diabetes developing by early midlife.
Immunizing Patients With Metastatic Melanoma Using Recombinant Adenoviruses Encoding MART-1 or gp100 Melanoma Antigens
Authors: S. A. Rosenberg, Y. Zhai, J. C. Yang, D. J. Schwartzentruber, P. Hwu, F. M. Marincola, S. L. Topalian, N. P. Restifo, C. A. Seipp, J. H. Einhorn, D. E. White, B. Roberts
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: The characterization of the genes encoding melanoma-associated antigens MART-1 or gp100, recognized by T cells, has opened new possibilitiesfor the development of immunization strategies for patients with metastatic melanoma. With the use of recombinant adenoviruses expressing either MART-1 or gp100 to immunize patients with metastatic melanoma, we evaluated the safety, immunologic, and potential therapeutic aspects of these immunizations. Methods: In phase I studies, 54 patients received escalating doses (between 10 7 and 10 11 plaque-forming units) of recombinant adenovirus encoding either MART-1 or gp100 melanoma antigen administered either alone or followed by the administration of interleukin 2 (IL-2). The immunologic impact of these immunizations on the development of cellular and antibody reactivity was assayed. Results: Recombinant adenoviruses expressing MART-1 or gp100 were safely administered. One of 16 patients with metastatic melanoma receiving the recombinant adenovirus MART-1 alone experienced a complete response. Other patients achieved objective responses, but they had received IL-2 along with an adenovirus, and their responses could be attributed to the cytokine. Immunologic assays showed noconsistent immunization to the MART-1 or gp100 transgenes expressed by the recombinant adenoviruses. High levels of neutralizing anti-body were found in the pretreatment sera of the patients. Conclusions: High doses of recombinant adenoviruses could be safely administered to cancer patients. High levels of neutralizing anti-body present in patients' sera prior to treatment may have impaired the ability of these viruses to immunize patients against melanoma antigens.
Pelvic Evisceration with Primary Bowel and Ureteric Anastomoses
Authors: G. E. Moloney
Journal: BMJ (1953)

Treatment of myxoedema in the last stages is ineffec- tive; therefore it is essential to diagnose and treat it early.Our thanks are due to Dr. A. J. Hardy, who performed the necropsy on Case 2 and allowed us to be present and gave facilities for histological examinations; to Dr. A.
Pesticide ban imposed after reports of congenital abnormalities
Authors: S. Kumar
Journal: BMJ (2002)

The Kerala High Court in southern India has reinstated a ban on the highly hazardous pesticide endosulfan, already banned in many countries, after growing concern at the risk of farmers and villagers being poisoned.

The news comes as an unpublished report, seen by the BMJ , shows the impact on villagers in the area.

At the behest of India's National Human Rights Commission, the Indian Council of Medical Research last year asked the National Institute of Occupational Health to investigate the pesticide's effects. The institute's report, finalised in March 2002, still remains confidential.

The report shows that water samples collected by …
Technetium-99m DMSA Abnormal Uptake by Metastatic Lesion of a Renal Cell Carcinoma
Authors: SHIGERU KOSUDA, YOSHISADA HIRONO, HARUHIKO YOSHINAGA, KENJI SAITO, KOHEI TAMURA, ATSUSHI KUBO, SHOZO HASHIMOTO
Journal: Clinical Nuclear Medicine (1986)

A case of renal cell carcinoma, clear cell type, with bone metastasis that took up Tc-99m DMSA in the presence of normal renal function is presented. The primary renal tumor, however, did not definitely show Tc-99m DMSA accumulation. The reason is probably that Tc-99m DMSA uptake by tumor cells is much less prominent than uptake by normal tubular cells. Our finding suggests that Tc-99m DMSA may have an affinity for some types of adenocarcinomas. The details of the tumor affinity mechanism of this agent still must be studied.
Inhibition of Tumor Growth and Metastasis by a Combination of Escherichia coli–mediated Cytolytic Therapy and Radiotherapy
Authors: Sheng-Nan Jiang, Thuy X Phan, Taek-Keun Nam, Vu H Nguyen, Hyung-Seok Kim, Hee-Seung Bom, Hyon E Choy, Yeongjin Hong, Jung-Joon Min
Journal: Molecular Therapy (2010)

We have reported that Escherichia coli K-12 colonizes hypoxic and necrotic tumor regions after intravenous injection into tumor-bearing mice. In this study, we established a novel strategy for cancer therapy using engineered bacteria to enhance the therapeutic effects of radiation. E. coli strain K-12 was engineered to produce cytolysin A (ClyA), and its effects on tumor growth in primary and metastatic tumor models were evaluated. A single treatment with E. coli–expressing ClyA significantly decreased tumor growth rates initially (9 days after treatment); however, the tumors tended to grow thereafter. With only radiotherapy (RT; 21 Gy), the tumor growth rates were retarded, but not the tumor sizes. A combination of therapy with E. coli–expressing ClyA and radiation [a total of 5 × 107 colony-forming units (CFU) and 21 Gy] resulted in significant tumor shrinkage and even complete disappearance of tumors in mice with tumors derived from murine CT26 colon cancer. Furthermore, treatment with E. coli–expressing ClyA markedly suppressed metastatic tumor growth and prolonged the survival time in mice. The results described here indicate that therapy with engineered E. coli could significantly improve the results of RT, and could exert a striking inhibitory effect on the development of lung metastasis. We have reported that Escherichia coli K-12 colonizes hypoxic and necrotic tumor regions after intravenous injection into tumor-bearing mice. In this study, we established a novel strategy for cancer therapy using engineered bacteria to enhance the therapeutic effects of radiation. E. coli strain K-12 was engineered to produce cytolysin A (ClyA), and its effects on tumor growth in primary and metastatic tumor models were evaluated. A single treatment with E. coli–expressing ClyA significantly decreased tumor growth rates initially (9 days after treatment); however, the tumors tended to grow thereafter. With only radiotherapy (RT; 21 Gy), the tumor growth rates were retarded, but not the tumor sizes. A combination of therapy with E. coli–expressing ClyA and radiation [a total of 5 × 107 colony-forming units (CFU) and 21 Gy] resulted in significant tumor shrinkage and even complete disappearance of tumors in mice with tumors derived from murine CT26 colon cancer. Furthermore, treatment with E. coli–expressing ClyA markedly suppressed metastatic tumor growth and prolonged the survival time in mice. The results described here indicate that therapy with engineered E. coli could significantly improve the results of RT, and could exert a striking inhibitory effect on the development of lung metastasis.
The anatomy of an arrhythmia
Authors: Robert F. Gilmour
Journal: Journal of Clinical Investigation (2004)

Computer simulations are potentially effective approaches to unraveling the causes of lethal heart rhythm disorders. In this issue of the JCI, Xie et al. have embedded a well-characterized dynamic mechanism for arrhythmia development in an anatomically realistic computer model of the heart. Their demonstration that this simple mechanism governs the behavior of the complex model may provide a new target for strategies to prevent sudden death.
Mechanical strain activates BNP gene transcription through a p38/NF-κB–dependent mechanism
Authors: Faquan Liang, David G. Gardner
Journal: Journal of Clinical Investigation (1999)

Application of mechanical strain to neonatal rat ventricular myocytes in culture evokes changes in gene expression reminiscent of those that occur with hypertrophy in vivo, such as stimulation of brain natriuretic peptide (BNP) gene expression. Here, we show that a major component of strain-dependent BNP promoter activation results from stimulation of p38 mitogen-activated protein kinase (MAPK) in the cardiac myocyte. Strain increased p38 activity in a time-dependent fashion. The p38 inhibitor SB203580 led to a reduction of approximately 60% in strain-activated human BNP (hBNP) promoter activity. Cotransfection of wild-type p38 increased both basal and strain-dependent promoter activity, while cotransfection with MKK6AL, a dominant-negative inhibitor of p38 MAPK kinase, resulted in partial inhibition of either p38- or strain-activated hBNP promoter activity. p38 MAPK increased hBNP promoter activity through activation of the transcription factor NF-κB. Activation of the hBNP promoter by either p38 or strain was mediated by DNA elements present in the 5′ flanking sequence of the gene. Mechanical strain promoted assembly of NF-κB components on these DNA elements in vitro. Thus, induction of the hBNP promoter by mechanical strain depends, at least in part, on stimulation of p38 and subsequent activation of NF-κB. This activation may play an important role in signaling the increased BNP gene expression that accompanies hemodynamic overload and cardiac hypertrophy in vivo.
Treatment of Depression
Authors: Mortimer Ostow
Journal: JAMA (1983)

<h3>To the Editor.—</h3> In an editorial entitled "Depressives, Doctors, and Antidepressants" in the Oct 15 issue, Dr E. H. Uhlenhuth hopes that basic and clinical research will "provide us with antidepressants that are more promptly effective, easier to use, safer, and more acceptable to patients." We already have two antidepressive agents that, although far from perfect, do meet those criteria. I refer to dextroamphetamine and methylphenidate hydrochloride. Administered by one of those who have taken the trouble to learn their properties, these substances will control the symptoms of depression in many patients promptly, safely, and without unpleasant adverse effects. It is true that some patients do not respond and others experience toxic reactions. However, these disadvantages are countered with all of the antidepressive drugs that are available, and they are no more frequently associated with the stimulant drugs than with the others. At the very least, the stimulants can be
SPECIAL INFLUENCES OF THE HIGH ALTITUDES ON THE NOSE AND THROAT.
Authors: S. EDWIN SOLLY
Journal: JAMA (1903)

The subject has, unfortunately, to be considered largely from the standpoint of hypothesis and theory, as at present the facts do not admit of absolute proof. Personally, as a physician without numerous hospital cases to study or a physiologic laboratory to experiment in, I find it impossible to prove the truth of the theories I may entertain in this matter. Though my opportunities for observing these phenomena have been comparatively few at any one time, they have extended over some twenty-eight years of practice in Colorado, and, therefore, have the value of single spies, though they can not have the weight of battalions. In rhinologic practice in Colorado one is struck with the fact that patients arriving from sea level often complain of nasal symptoms of which they had not been conscious at home. The reasons for this undoubted fact appear to me as follows: In the first
Activation of Human B Lymphocytes after Immunization with Pneumococcal Polysaccharides
Authors: John K. Kehrl, Anthony S. Faucl
Journal: Journal of Clinical Investigation (1983)

The in vivo and in vitro immune response after in vivo immunization with pneumococcal polysaccharides (PPS) has been analyzed in man. Substantial differences were noted in this system when compared with human responses to soluble protein antigens. Within 6 d after immunization, specific PPS antigen-binding cells (ABC), specific plaque-forming cells (PFC), and cells capable of spontaneously synthesizing in vitro large amounts of specific anti-PPS immunoglobulin (Ig) G. IgA, and lesser amounts of specific IgM appeared in the peripheral blood. The ABC, PFC, and the total amount of specific spontaneous antibody production followed nearly identical kinetics after immunization. Low doses of irradiation markedly inhibited spontaneous anti-PPS antibody production by lymphocytes obtained 7 or 8 d after immunization, suggesting a requirement for in vitro proliferation for full expression of antibody-secreting capability of these cells that are activated in vivo and are capable of spontaneous antibody production in vitro. Spontaneous secretion by B lymphocytes in vitro was independent of T cells, unmodified by the addition of T cell factors, and readily suppressible by pokeweed mitogen (PWM).
Neointimal thickening after balloon denudation is enhanced by aldosterone and inhibited by spironolactone, and aldosterone antagonist
Authors: E. Van Belle, C. Bauters, N. Wernert, M. Hamon, E. P McFadden, A. Racadot, B. Dupuis, J.-M. Lablanche, M. E Bertrand
Journal: Cardiovascular Research (1995)

Objective: The aim was to examine the effects of aldosterone and of an aldosterone antagonist, spironolactone, on neointimal thickening in a rabbit model of balloon injury. Methods: Eighteen rabbits underwent aortic and iliac balloon injury and were randomised to subcutaneous infusion of aldosterone (70 μg·kg−1·d-t-1) or vehicle solution for 28 d. Eighteen other rabbits were randomised to receive daily subcutaneous injections of spironolactone (50 mg·kg−1·d−1) or of vehicle for 7 d before injury and for 28 d after the procedure. All animals were then killed just after measurement of plasma renin activity and of arterial pressure. Vessels were fixed and five cross sections were analysed per rabbit (three aortic; two from iliac artery). Mean values of neointimal area and of the neointimal area/medial area ratio were calculated. Results: Aldosterone treatment was associated with a decrease in renin activity and a non-significant increase in mean arterial pressure. Aldosterone significantly augmented the neointimal thickening in the iliac artery [0.42(SEM 0.07) v 0.24(0.03) mm2, P < 0.05]but not in the aorta [0.63(0.08) v 0.59(0.12) mm2, NS]. Spironolactone significantly inhibited intimal thickening, both in the iliac artery [0.09(0.02) v 0.29(0,01) mm2, P < 0.001]and in the aorta [0.31(0.03) v 0.59(0.06) mm2, P < 0.001]. Spironolactone administration was associated with an increase in renin activity and a decrease in mean arterial blood pressure. Conclusions: Aldosterone administration enhances neointimal thickening after injury and spironolactone, an aldosterone antagonist, is a potent inhibitor of neointimal thickening in the same model. This suggests a role for aldosterone in the pathophysiology of neointimal proliferation after balloon injury and for aldosterone antagonists in its prevention.
Regularities in motion: Apparent, real and internalized
Authors: Robert Schwartz
Journal: Behavioral and Brain Sciences (2001)

By and large the commentators express reservations similar to my own concerning Shepard's position. Some focus on the issue of ecological validity, others are skeptical of Shepard's evolutionary thesis. The assumptions and reasons for their criticisms, however, are not always ones I fully accept. In addition, several commentators, although rejecting Shepard's particular claims, support his overall approach. They offer models for motion perception and for phenomena in other domains that they feel are amenable to treatment along Shepard's lines. I examine the pros and cons of the commentators' analyses of Shepard. I also briefly evaluate aspects of their alternative proposals.
Detection of endometrial cancer in postmenopausal women:Authors' reply
Authors: T H Bourne, S Campbell, W P Collins
Journal: BMJ (1990)

general gynaecological practice is usually 5-10%.Finally, women attending a menopause clinic as controls may not represent a reasonable sample of the normal population and this may have biased the results for comparison, as these women are known to experience symptoms that are a conse- quence of vasomotor instability.With these facts in mind I believe that it is inappropriate to consider such variables as detection rates, predictive values, and odds ratios.I await with interest, however, the results of the definitive, well controlled study to evaluate the role of transvaginal ultrasonography and colour flow imaging in the detection of endometrial carcinoma.