tbuckley/cabot-search huggingface dataset:
Preventive and therapeutic effects in rats of hepatocyte growth factor infusion on liver fibrosis/cirrhosis
Authors: Y Matsuda
Journal: Hepatology (1997)

Liver fibrosis/cirrhosis is characterized by hyper-accumulation of fibrous tissue components and is commonly observed in later or terminal states of chronic hepatic diseases. In ongoing work, we found that the administration of human recombinant hepatocyte growth factor (hrHGF) suppressed the onset of liver fibrosis/cirrhosis in several distinct models and accelerated the recovery from liver fibrosis/cirrhosis in rats. Repeated administration of porcine serum for 10 weeks to rats induced liver fibrosis without any accompanying hepatocellular injuries; in addition, the intravenous (i.v.) administration of hepatocyte growth factor (HGF) to these rats suppressed increases in fibrous components and hydroxyproline contents in the liver, thus preventing the onset of liver fibrosis. Repeated administration of dimethylnitrosamine (DMN) for four weeks induced liver cirrhosis, as characterized by the hyper-accumulation of fibrous components, infiltration of mononuclear leukocytes, and hepatic dysfunction. When HGF was injected daily for four weeks along with DMN-treatment, the onset of DMN-induced hepatic fibrosis/cirrhosis was suppressed; the numbers of infiltrating mononuclear cells, fibrous tissue components, and hydroxyproline content in the liver were decreased. When HGF was injected for two weeks following four weeks of DMN-treatment, HGF accelerated the recovery from liver cirrhosis and prevented death due to hepatic dysfunction. Likewise, HGF-injection suppressed the onset of liver fibrosis, when liver fibrosis had been induced by long-term treatment with carbon tetrachloride (CCl4). Thus, the administration of HGF holds great promise for treating subjects with liver fibrosis/cirrhosis as a result of chronic hepatic injury.
The Twiddler Syndrome
Authors: W A L Tonino, J B Winter
Journal: New England Journal of Medicine (2006)

A 55-year-old woman received a diagnosis of the sick sinus syndrome. A dual-chamber pacemaker was implanted with one lead in the right atrium and the other lead in the right ventricle (Panel A). The leads were inserted without complication through the left cephalic vein and secured with sutures. One week after implantation, the pacemaker functioned well. Two weeks later, the patient visited the emergency room with a report of stimulation of the diaphragm. A radiograph of the chest demonstrated displacement of both leads, with winding of the leads around the pacemaker box (Panel B, arrow). The patient reported having twisted . . .
Gut-derived commensal bacterial products inhibit liver dendritic cell maturation by stimulating hepatic interleukin-6/signal transducer and activator of transcription 3 activity
Authors: John G. Lunz, Susan M. Specht, Noriko Murase, Kumiko Isse, Anthony J. Demetris
Journal: Hepatology (2007)

Intraorgan dendritic cells (DCs) monitor the environment and help translate triggers of innate immunity into adaptive immune responses. Liver-based DCs are continually exposed, via gut-derived portal venous blood, to potential antigens and bacterial products that can trigger innate immunity. However, somehow the liver avoids a state of perpetual inflammation and protects central immune organs from overstimulation. In this study, we tested the hypothesis that hepatic interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) activity increases the activation/maturation threshold of hepatic DCs toward innate immune signals. The results show that the liver nuclear STAT3 activity is significantly higher than that of other organs and is IL-6–dependent. Hepatic DCs in normal IL-6 wild-type (IL-6+/+) mice are phenotypically and functionally less mature than DCs from IL-6–deficient (IL-6−/−) or STAT3-inhibited IL-6+/+ mice, as determined by surface marker expression, proinflammatory cytokine secretion, and allogeneic T-cell stimulation. IL-6+/+ liver DCs produce IL-6 in response to exposure to lipopolysaccharide (LPS) and cytidine phosphate guanosine oligonucleotides (CpG) but are resistant to maturation compared with IL-6−/− liver DCs. Conversely, exogenous IL-6 inhibits LPS-induced IL-6−/− liver DC maturation. IL-6/STAT3 signaling influences the liver DC expression of toll-like receptor 9 and IL-1 receptor associated kinase-M. The depletion of gut commensal bacteria in IL-6+/+ mice with oral antibiotics decreased portal blood endotoxin levels, lowered the expression of IL-6 and phospho-STAT3, and significantly increased liver DC maturation. Conclusion: Gut-derived bacterial products, by stimulating hepatic IL-6/STAT3 signaling, inhibit hepatic DC activation/maturation and thereby elevate the threshold needed for translating triggers of innate immunity into adaptive immune responses. Manipulating gut bacteria may therefore be an effective strategy for altering intrahepatic immune responses. (Hepatology 2007.)
The Fetal Alcohol Syndrome-Reply
Authors: James W. Hanson
Journal: JAMA (1976)

We certainly agree with the conclusion of Drs Mankad and Choksi that alcohol is a powerful teratogen in animals. It is equally potent in man. Although the summary of findings in infants with the fetal alcohol syndrome that we presented in our article was uncontrolled, previous studies were not. One case-control study of the effects of maternal heavy alcohol consumption on the outcome of pregnancy has been previously reported<sup>1</sup>; another is in progress to assess possible additive effects of concurrent smoking and the use or abuse of other drugs. As pointed out by Drs Mankad and Choksi, it is difficult to conduct an ideally controlled study of these latter relationships. However, we would emphasize that no overall pattern such as we have described in these infants has ever been attributed to the effects of smoking or to the use of illicit drugs, despite a number of investigations.
Clinical Evaluation of a Rosette Inhibition Test in Renal Allotransplantation
Authors: A. Munro, M. Bewick, L. Manuel, J. S. Cameron, F. G. Ellis, M. Boulton-Jones, C. S. Ogg
Journal: BMJ (1971)

The formation of spontaneous rosettes by peripheral blood or spleen mononuclear cells when incubated with sheep red blood cells has proved a useful way of assessing the potency of immunosuppressive drugs and antilymphocyte sera in vitro. A test employing the inhibition by antilymphocyte globulin (A.L.G.) of spontaneous rosette formation around peripheral blood mononuclear cells is described. This has been used to assess the degree of immunosuppression in patients with renal allografts and uraemic patients on regular haemodialysis.Twenty-three patients with renal allografts had 21 clinically diagnosed episodes of rejection. In none of these rejection episodes was the minimal inhibitory concentration (M.I.C.) of A.L.G. (that necessary to reduce the spontaneous rosette formation of peripheral cells by 75%) less than 1/50,000. Nineteen patients had no rejection episodes during 57 patient/months of continuous observation while the M.I.C. was at a greater dilution than 1/50,000. The test has therefore been of great value in suggesting when an individual is capable of rejecting his graft, and allows the dose of immunosuppressive drugs to be adjusted to a minimum in a controlled fashion. It has been of use in diagnosing rejection in the anuric patient, when the distinction between rejection, urinary tract obstruction, and infection is particularly difficult.Fifteen patients maintained on regular haemodialysis for more than a year had, as judged by this technique, less reactive lymphocytes than normal healthy controls. The degree of immunosuppression was not as great as in the patients on full immunosuppressive regimens.
Inactivation of the <i>CDKN2A</i> Tumor-Suppressor Gene by Deletion or Methylation Is Common at Diagnosis in Follicular Lymphoma and Associated with Poor Clinical Outcome
Authors: Abdulmohsen Alhejaily, Andrew G. Day, Harriet E. Feilotter, Tara Baetz, David P. LeBrun
Journal: Clinical Cancer Research (2014)

Follicular lymphoma, the most common indolent lymphoma, is clinically heterogeneous. CDKN2A encodes the tumor suppressors p16(INK4a) and p14(ARF) and frequently suffers deleterious alterations in cancer. We investigated the hypothesis that deletion or hypermethylation of CDKN2A might identify follicular lymphoma cases with distinct clinical or pathologic features potentially amenable to tailored clinical management.Deletion of CDKN2A was detected in pretreatment biopsy specimens using a single nucleotide polymorphism-based approach or endpoint PCR, and methylation of CpG elements in CDKN2A was quantified by methylation-specific PCR. Correlations between CDKN2A status and pathologic or clinical characteristics, including overall survival (OS), were investigated in 106 cases using standard statistical methods.Deletion of CDKN2A was detected in 9 of 111 samples (8%) and methylation was detectable in 22 of 113 (19%). CDKN2A was either deleted or methylated in 29 of 106 cases (27%) and this status was associated with inferior OS especially among patients treated with rituximab (P = 0.004). CDKN2A deletion or methylation was associated with more advanced age (P = 0.012) and normal hemoglobin (P = 0.05) but not with sex, FLIPI score, ECOG stage, LDH, performance status, number of involved nodal sites, B symptoms, histologic grade, the presence of a component of diffuse large B-cell lymphoma, proliferation index, or other pathologic factors.Our results show that deletion or methylation of CDKN2A is relatively common in pretreatment follicular lymphoma biopsy specimens and defines a group of cases associated with reduced survival in the rituximab era presumably on the basis of more aggressive disease biology.
Simple Method for Insertion of Small Feeding Tube
Authors: Harry S. Goldsmith
Journal: New England Journal of Medicine (1961)

FREQUENTLY seen on medical and surgical wards are patients who have increased nutritional demands for tissue production and for the maintenance of life. Some examples of these situations are patients who have had severe debilitation before and after operation, long standing wasting diseases, coma and bulbar poliomyelitis with paralysis of the swallowing apparatus. Intravenous feedings with these conditions after a prolonged period become ineffectual in terms of nutritional intake and in the mechanical difficulties that eventually arise.It has been generally accepted that feeding through an indwelling nasogastric tube is satisfactory when the situation so demands. Various-sized Levin tubes are . . .
Direct and Natural Killer Cell-Mediated Antitumor Effects of Low-Dose Bortezomib in Hepatocellular Carcinoma
Authors: Sorin Armeanu, Matthias Krusch, Katrin M. Baltz, Thomas S. Weiss, Irina Smirnow, Alexander Steinle, Ulrich M. Lauer, Michael Bitzer, Helmut R. Salih
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Hepatocellular carcinoma (HCC) displays particular resistance to conventional cytostatic agents. Alternative treatment strategies focus on novel substances exhibiting antineoplastic and/or immunomodulatory activity enhancing for example natural killer (NK) cell antitumor reactivity. However, tumor-associated ligands engaging activating NK cell receptors are largely unknown. Exceptions are NKG2D ligands (NKG2DL) of the MHC class I-related chain and UL16-binding protein families, which potently stimulate NK cell responses. We studied the consequences of proteasome inhibition with regard to direct and NK cell–mediated effects against HCC. Experimental Design: Primary human hepatocytes (PHH) from different donors, hepatoma cell lines, and NK cells were exposed to Bortezomib. Growth and viability of the different cells, and immunomodulatory effects including alterations of NKG2DL expression on hepatoma cells, specific induction of NK cell cytotoxicity and IFN-γ production were investigated. Results: Bortezomib treatment inhibited hepatoma cell growth with IC50 values between 2.4 and 7.7 nmol/L. These low doses increased MICA/B mRNA levels, resulting in an increase of total and cell surface protein expression in hepatoma cells, thus stimulating cytotoxicity and IFN-γ production of cocultured NK cells. Importantly, although NK cell IFN-γ production was concentration-dependently reduced, low-dose Bortezomib neither induced NKG2DL expression or cell death in PHH nor altered NK cell cytotoxicity. Conclusions: Low-dose Bortezomib mediates a specific dual antitumor effect in HCC by inhibiting tumor cell proliferation and priming hepatoma cells for NK cell antitumor reactivity. Our data suggest that patients with HCC may benefit from Bortezomib treatment combined with immunotherapeutic approaches such as adoptive NK cell transfer taking advantage of enhanced NKG2D-mediated antitumor immunity.
Peripheral resistance after cardiac output reduction in the barodenervated cat.
Authors: P Borgdorff
Journal: Circulation Research (1983)

Studies on the nervous or humoral control of total peripheral resistance are often complicated by concomitant changes in cardiac output. We studied the influence of cardiac output on peripheral resistance in the absence of modulating reflexes. In barodenervated and vagotomized cats, cardiac output was varied by graded inferior caval vein occlusion or by arterial bleeding. Total peripheral resistance was obtained with an analogue device which continuously divided the pressure difference between aorta and caval vein by cardiac output (electromagnetic flowmeter). Cardiac output reduction caused a decrease of peripheral resistance, followed within 2 minutes by a slow increase. Resistance stabilized at preocclusion levels within 5.8 (range 4-9) minutes. The relative changes in resistance and cardiac output were linearly related, when cardiac output was reduced by less than 40%. With larger reductions, the relation became nonlinear, and with a drop of more than 65%, no further change was noticed. These changes in resistance could not be explained by variations in blood viscosity as measured by Hct. They were nonnervous in nature: when all reflexes were abolished by ganglionic blockade, a similar pattern was found. Humoral mechanisms like the vasopressin or the renin-angiotensin system, known to be activated by hypotension, probably played no role, since arterial osmolality remained stable and captopril did not influence the resistance response. The involvement of metabolic autoregulation could not be excluded, but was unlikely because O2 consumption and serum lactate did not change.
Epinephrine for Treatment of Anaphylactic Shock
Authors: Eric M. Barach, Richard M. Nowak, Tennyson G. Lee, Michael C. Tomlanovich
Journal: JAMA (1984)

SYSTEMIC anaphylactic shock is a medical emergency caused by the release of chemical substances in response to an antigenic stimulus in a previously sensitized person. This stimulus may be food, drugs, blood products, insect venom, or exposure to pollens. Epinephrine has been considered the drug of choice in this emergency. A patient was initially seen in systemic anaphylactic shock secondary to a bee sting and was treated with intravenous (IV) epinephrine. Although the dose used was within the acceptable range advocated by many authors, there were serious early and delayed consequences associated with its use. This led to a review of the literature concerning the use of IV epinephrine in treating systemic anaphylactic shock. The potential problems inherent in uncritically accepting the current recommendations for therapy with IV epinephrine are discussed.  Report of a Case  A 34-year-old previously healthy man was admitted to the emergency department with complaints of rapid
Vagal system impairment in HIV-positive patients with chronic hepatitis C: has hepatic glutathione deficiency a pathogenetic role?
Authors: Giuseppe Barbaro, Gabriella Di lorenzo, Maurizio Soldini, Giorgio Bellomo, Giancarlo Belloni, Benvenuto Grisorio, Giovanni Rizzo, Francesca Cadario, Giorgio Barbarini
Journal: Journal of Hepatology (1998)
p48 Overexpression enhances interferon-mediated expression and activity of double-stranded RNA-dependent protein kinase in human hepatoma cells
Authors: Yoko Tamada, Kazuhiko Nakao, Yuji Nagayama, Keisuke Nakata, Tatsuki Ichikawa, Yosei Kawamata, Hiroki Ishikawa, Keisuke Hamasaki, Katsumi Eguchi, Nobuko Ishii
Journal: Journal of Hepatology (2002)
Seroprevalence of HIV and Risk Behaviors Among Young Homosexual and Bisexual Men
Authors: G F Lemp, A M Hirozawa, D Givertz, G N Nieri, L Anderson, M L Lindegren, R S Janssen, M Katz
Journal: JAMA (1994)

To estimate the prevalence of human immunodeficiency virus (HIV) infection and risk behaviors among young homosexual and bisexual men sampled from public venues in San Francisco and Berkeley, Calif.A survey of 425 young homosexual and bisexual men sampled from 26 locations during 1992 and 1993. Participants were interviewed and blood specimens were drawn and tested for HIV, level of CD4+ T lymphocytes, and markers of hepatitis B and syphilis.Public venues in San Francisco and Berkeley, including street corners and sidewalks, dance clubs, bars, and parks.Homosexual and bisexual men aged 17 to 22 years.Prevalence of HIV infection and risk behaviors.The HIV seroprevalence was 9.4% (95% confidence interval, 6.8% to 12.6%). The prevalence of markers for hepatitis B was 19.8% (95% confidence interval, 16.1% to 23.9%), and that for syphilis was 1.0% (95% confidence interval, 0.3% to 2.4%). The HIV seroprevalence was significantly higher among African Americans (21.2%) than among other racial/ethnic groups (P = .002). Approximately one third (32.7%) of the participants reported unprotected anal intercourse, and 11.8% reported injecting drug use in the previous 6 months. At the time of interview, 70.0% of the HIV-infected men did not know that they were HIV seropositive, and only 22.5% were receiving medical care for HIV infection.The prevalence of HIV infection is high among this young population of homosexual and bisexual men, particularly among young African-American men. The high rates of HIV-related risk behaviors suggest a considerable risk for HIV transmission in this population. Prevention programs and health services need to be tailored to address the needs of a new generation of homosexual and bisexual men.
Abstract 91: Powerful inhibition of human renal cell carcinomas with antagonists of growth hormone-releasing hormone (GHRH): a preclinical study.
Authors: Ferenc G. Rick, Andrew Abi-Chaker, Luca Szalontay, Norman L. Block, Gabor Halmos, Mehrdad Nadji, Andrew V. Schally
Journal: Cancer Research (2013)

Abstract BACKGROUND: Advances in targeted medical thereapy has demonstrated improved clinical outcomes for patients with metastatic renal cell carcinoma (RCC), however, a complete response is rare and current therapy has various adverse effects that are unfortunately not as rare. Early antagonists of growth hormone-releasing hormone (GHRH) were shown to inhibit experimental RCC cell line, Caki-1, in vitro and in vivo. GHRH itself acts as an autocrine/paracrine growth factor in human cancers, including RCC. Herein, we investigate the effects of novel and highly potent new antagonists of GHRH on the growth of three RCC cell lines with different primary tumor sites. METHODS: The expression of GHRH receptor in all three cell lines was evaluated by ligand competition studies. The in vitro influence of GHRH antagonists designated MIA-602, MIA-604, MIA-606 and MIA-690 on cell viability was assessed by MTS assay in ACHN, A498, and 786-0 human RCC cells. GHRH antagonists were given at a dose of 5μg daily in these three nude-mice xenograft models in vivo. Cell cycle parameters were analyzed by laser flow cytometry. RESULTS: Ligand competition studies revealed specific, high affinity binding sites for GHRH receptor in all three RCC cell lines. GHRH antagonists inhibited the proliferation of all three RCC cells in a dose dependent manner. GHRH antagonists caused significant inhibition of tumor growth of ACHN, A498, and 786-0 RCCs ranging from 53-75% after 35 days of treatment (p&amp;lt;0.001). Treatment of ACHN and A498 cells with 10μM MIA-602 and MIA-690 (5 and 10μM) led to a significant increase in number of cells with subG1 DNA content, suggesting apoptosis. CONCLUSIONS: The effectiveness of the new and novel GHRH antagonists in inhibiting growth of experimental RCC models in vitro and in vivo was demonstrated. The inhibitory effect of GHRH antagonists is mainly due to direct suppressive effects exerted through GHRH receptors. Further biochemical and histological evaluation is warranted to explore the mechanisms of action of GHRH antagonists in RCC. Citation Format: Ferenc G. Rick, Andrew Abi-Chaker, Luca Szalontay, Norman L. Block, Gabor Halmos, Mehrdad Nadji, Andrew V. Schally. Powerful inhibition of human renal cell carcinomas with antagonists of growth hormone-releasing hormone (GHRH): a preclinical study. [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 91. doi:10.1158/1538-7445.AM2013-91
<sup>11</sup>C-Labeled Methionine and Evaluation of Malignant Pleural Mesothelioma
Authors: Giovanni L. Ceresoli, Arturo Chiti, Armando Santoro
Journal: New England Journal of Medicine (2007)

To the Editor: Assessing responses to treatment on the basis of computed tomographic (CT) measurements in patients with malignant pleural mesothelioma is challenging because of the pattern of growt...
Sadistic cruelty and unempathic evil: Psychobiological and evolutionary considerations
Authors: Dan J. Stein
Journal: Behavioral and Brain Sciences (2006)

Understanding the origins of evil behaviour is one of our most important intellectual tasks. A distinction can perhaps be drawn between overt sadistic cruelty and the lack of empathy to suffering that is a hallmark of evil. There is increasing data available on the prevalence, proximal psychobiological underpinnings, and distal evolutionary basis for these contrasting phenomena.
The senile epidermis: environmental influences on skin ageing and cutaneous carcinogenesis
Authors: G. S. ROGERS, B. A. GILCHREST
Journal: British Journal of Dermatology (1990)

There is a wealth of new knowledge regarding mechanisms of carcinogenesis and their interaction with senescence and environmental insults, particularly on the effects of UV irradiation on the skin. Innovations and advances in tissue culture techniques now permit in vitro studies of keratinocytes and other benign and malignant skin‐derived cells. The ageing processes and cutaneous neoplasia, therefore, can now be studied at the cellular level. New insights regarding the interrelationship of ageing, environment and cutaneous neoplasia are close at hand. Depletion in the number of Langerhans cells and suppression of their function in ageing and UV‐exposed skin may allow tumour cells to overcome the host's defence system. The potential increase in UV irradiation due to depletion of the ozone layer may increase the incidence of skin tumours. Carcinogenesis involves three distinct steps: initiation, promotion, and malignant conversion. The mechanism has been studied in mice, where it is suggested the c‐ras oncogene may play an important role.
Towards a Unified Filing System
Authors: T. Healey
Journal: BMJ (1970)

MDICALJU 277 tional conditions certainly reduced the number of patients graded as "improved by recommendations made," but the extent to which this is so cannot be assessed and, as we are making a conservative estimate of the value of our activities, we have left this factor out of our calculations.Of all the patients originally examined 17",', required regular follow-up by health visitors or at day hospital or outpatient departments, and this also indicates a clear level of unmet need.