tbuckley/cabot-search huggingface dataset:
In vivo response of hepatocytes to growth factors requires an initial priming stimulus
Authors: Eric M. Webber, Paul J. Godowski, Nelson Fausto
Journal: Hepatology (1994)

Although growth factor effects have been studied in cultured hepatocytes, little information exists as to whether these factors can trigger hepatocyte replication in vivo . In this study we infused epidermal growth factor, transforming growth factor-α and hepatocyte growth factor directly into the portal vein of rats for 24 hr to see whether they could induce DNA synthesis in normal livers or in livers subjected to one-third hepatectomy. Infusion of transforming growth factor-α or epidermal growth factor at doses up to 80 μg/24 hr had little effect on hepatic DNA synthesis in normal liver, whereas the monomeric and heterodimeric forms of hepatocyte growth factor generally produced increases of less than threefold in hepatic DNA synthesis. In contrast, after one-third hepatectomy infusion of epidermal growth factor, transforming growth factor-α or hepatocyte growth factor produced dose-dependent increases in hepatic DNA synthesis. At a dose of 40 μg/24 hr, epidermal growth factor increased DNA synthesis threefold, whereas transforming growth factor-α or hepatocyte growth factor increased DNA synthesis to greater than six times that in rats that had undergone hepatectomy alone. Furthermore, infusion of these growth factors, with or without one third-hepatectomy, induced the expression of transforming growth factor-α mRNA in the liver. The pattern of protooncogene expression induced by one-third hepatectomy was studied to determine the effect of this procedure in sensitizing the liver to the growth factors. Compared with the well-characterized two-thirds hepatectomy system, there was a similar but smaller increase in c- myc expression but no induction of c- jun expression. The results suggest that a small functional deficit in the liver that by itself causes little DNA synthesis “primes” hepatocytes for replication and that the loss of liver mass and growth factor infusions complement each other by providing essential stimuli needed for DNA synthesis. (Hepatology 1994;14:489-497).
Protective Effect of Propylthiouracil Independent of Its Hypothyroid Effect on Atherogenesis in Cholesterol-Fed Rabbits
Authors: Wei-Jan Chen, Kwang-Huei Lin, Ying-Ju Lai, Su-Hui Yang, Jong-Hwei S. Pang
Journal: Circulation (2004)

Propylthiouracil (PTU) is used to treat hyperthyroid patients by its hypothyroid effect. PTU also is found to have potent antioxidant and immunosuppressive effects. These findings suggest that PTU may play a role in the prevention of atherosclerosis.This study evaluates the effect of PTU on atherosclerotic change in rabbits fed a high-cholesterol diet. The pronounced atherosclerotic lesions in the aortas of rabbits fed a 2% cholesterol diet for 12 weeks were significantly attenuated by the concurrent addition of 0.1% PTU to the drinking water. However, exogenous supplementation of thyroid hormone in hypothyroid PTU-treated rabbits did not abrogate the protective effect of PTU on atherogenesis. Immunohistochemical analysis showed that PTU administration apparently reduced the intimal smooth muscle cell/macrophage ratio in the atherosclerotic plaques of rabbits fed a 2% cholesterol diet. In vitro, the addition of PTU to the medium of cultured rat vascular smooth muscle cells led to a dose-dependent inhibition of cell proliferation and migration. Furthermore, this study confirmed that PTU dose-dependently increased expression of PTEN, a tumor suppressor gene known to be involved in the coordinate inhibition of VSMC proliferation and migration.This study demonstrated that PTU inhibited the development of atherosclerosis through a thyroid-independent mechanism that may be explained, at least in part, by the ability of PTU to inhibit vascular smooth muscle cell proliferation and migration. Furthermore, PTEN induction, via disruption of the phosphatidylinsitol 3-kinase-mediated pathway, plays a crucial role in mediating the inhibitory action on vascular smooth muscle cell proliferation and migration.
Quality of life after gastrectomy for cancer evaluated via the EORTC QLQ-C30 and QLQ-STO22 questionnaires: surgical considerations from the analysis of 103 patients
Authors: Stefano Rausei, Alberto Mangano, Federica Galli, Francesca Rovera, Luigi Boni, Gianlorenzo Dionigi, Renzo Dionigi
Journal: International Journal of Surgery (2013)
Abstract P013: N-6 And N-3 Fatty Acid Cholesteryl Esters In Relation To Fatal Chd In A Dutch Adult Population: A Nested Case-control Study
Authors: Janette de Goede, WM Monique Verschuren, Jolanda MA Boer, Lisa DM Verberne, Daan Kromhout, Johanna M Geleijnse
Journal: Circulation (2012)

Aim: Dietary polyunsaturated fatty acids (PUFA) are inversely related to coronary heart disease (CHD) in epidemiological studies. We examined the associations of plasma n-6 and n-3 PUFA in cholesteryl esters with fatal CHD in a nested case-control study. Methods We used data from two population-based cohort studies in Dutch adults aged 20-65 years. Blood sampling and data collection took place from 1987–1997 and subjects were followed for 8–19 years. We identified 279 incident cases of fatal CHD (235 fatal myocardial infarctions and 44 cardiac arrests) and randomly selected 279 controls, matched on age, gender, and enrollment date. Odds ratios (OR) with 95% confidence intervals (95%CI) were calculated per standard deviation (SD) increase of fatty acids in cholesteryl esters using multivariable conditional logistic regression models. Results After adjustment for confounders, the OR (95% CI) for fatal CHD per SD increase in plasma linoleic acid was 0.89 (0.74-1.06). Additional adjustment for plasma total cholesterol and systolic blood pressure attenuated this association (OR: 0.95; 95% CI: 0.78–1.15). Plasma arachidonic acid was not associated with fatal CHD (OR per SD: 1.11; 95% CI: 0.92-1.35). The ORs (95% CI) for fatal CHD for an SD increase in n-3 PUFA were 0.92 (0.74-1.15) for plasma alpha-linolenic acid and 1.06 (0.88-1.27) for plasma EPA-DHA. Conclusion In this Dutch adult population, arachidonic acid and n-3 PUFA in cholesteryl esters were not related to fatal CHD. Our data support findings from previous prospective studies showing a lower proportion of linoleic acid in plasma cholesteryl esters in CHD cases.
Histamine-2 Receptor Antagonists Do Not Alter Serum Ethanol Levels in Fed, Nonalcoholic Men
Authors: Jean-Pierre Raufman
Journal: Annals of Internal Medicine (1993)

Objective: To determine whether the four histamine-2 receptor antagonists currently available for the treatment of acid-peptic disorders in the United States alter serum ethanol levels after moderate alcohol consumption. Design: Prospective, randomized crossover design comparing the effects of histamine-2 receptor antagonists and no treatment on serum ethanol levels. Each participant served as his own control. Participants: Twenty-five healthy nonalcoholic men (21 to 35 years old); two participants were withdrawn before starting the study. Setting: University medical center. Intervention: Cimetidine (400 mg twice daily), famotidine (20 mg twice daily), nizatidine (150 mg twice daily), ranitidine (150 mg twice daily), and no treatment for 7 days. After the last dose of medication, participants ate a standard meal; 1 hour later they drank ethanol (0.3 g/kg body weight in 500 mL of orange juice) over 8 minutes. Measurements: Simultaneous measurements of breath and serum (headspace gas chromatography) ethanol were made before and 10, 20, 30, 45, 60, 90, 120, 150, and 180 minutes after ingestion of ethanol. Results: Peak ethanol levels did not differ (mmol/L; mean ± SE) after cimetidine (3.0 ± 0.3), famotidine (2.9 ± 0.3), nizatidine (2.9 ± 0.3), ranitidine (3.1 ± 0.4), and no treatment (2.9 ± 0.4). Similarly, there was no difference in the area under the curve (mmol/L x h; mean ± SE) after cimetidine (4.3 ± 0.5), famotidine (3.8 ± 0.4), nizatidine (4.2 ± 0.5), ranitidine (3.9 ± 0.4), and no treatment (4.0 ± 0.5). Conclusions: In healthy nonalcoholic men, the histamine-2 receptor antagonists currently available in the United States do not alter serum ethanol levels following moderate alcohol consumption after an evening meal.
ARE TRANQUILIZER COMBINATIONS MORE EFFECTIVE THAN A SINGLE TRANQUILIZER?
Authors: D. R. TALBOT
Journal: American Journal of Psychiatry (1964)

This study sought to assess the common practice of combination tranquilizer therapy in chronic psychotics. Conducted under double-blind conditions, it compared the efficacy and side effects from 3 regimens over a course of 8 months: 1. Chlorpromazine plus trifluoperazine; 2 Chlorpromazine plus trifluoperazine placebo; and 3. Trifluoperazine plus chlorpromazine placebo. It showed that with the two drugs combined efficacy was greater than with these drugs used individually. It showed, too, that with the drugs in combination side effects were about half what they were with trifluoperazine and not much more than they were with chlorpromazine (18% and 12% respectively). Therefore, from this study, it appears that the combination of chlorpromazine and trifluoperazine offers advantages in patients who do not respond to treatment with a single tranquilizer or who develop limiting side effects on high doses of a single tranquilizer.
Selective intracellular delivery of proteasome inhibitors through pH-sensitive polymeric micelles directed to efficient antitumor therapy
Authors: S. Quader, H. Cabral, Y. Mochida, T. Ishii, X. Liu, K. Toh, H. Kinoh, Y. Miura, N. Nishiyama, K. Kataoka
Journal: Journal of Controlled Release (2014)

The ubiquitin–proteasome system is central in the regulation of cellular proteins controlling cell cycle progression and apoptosis, drawing much interest for developing effective targeted cancer therapies. Herein, we developed a novel pH-responsive polymeric-micelle-based carrier system to effectively deliver the proteasome inhibitor MG132 into cancer cells. MG132 is covalently bound to the block copolymer composed of polyethylene glycol (PEG) and polyaspartate through an acid-labile hydrazone bond. This bond is stable at physiological condition, but hydrolytically degradable in acidic compartments in the cell, such as late-endosomes and lysosomes, and thus, it was used for controlled release of MG132 after EPR-mediated preferential accumulation of the micelles into the tumor. MG132-loaded micelles have monodispersed size distribution with an average diameter of 45 nm, and critical micelle concentration is well below 10− 7 M. In vitro studies against several cancer cell lines confirmed that MG132-loaded micelles retained the cytotoxic effect, and this activity was indeed due to the inhibition of proteasome by released MG132 from the micelles. Real-time in vitro confocal-microscopy experiments clearly indicated that MG132-conjugated micelles disintegrated only inside the target cells. By intravital confocal micro-videography, we also confirmed the prolonged circulation of MG132 loaded micelles in the bloodstream, which lead to tumor specific accumulation of micelles, as confirmed by in vivo imaging 24 h after injection. These micelles showed significantly lower in vivo toxicity than free MG132, while achieving remarkable antitumor effect against a subcutaneous HeLa-luc tumor model. Our findings create a paradigm for future development of polymeric-micelle-based carrier system for other peptide aldehyde type proteasome inhibitors to make them effective cohort of the existing cancer therapeutic regiments.
Blood Disorders in Childhood
Authors: M. C. G. Israels
Journal: BMJ (1963)

This is a large volume that starts off with an introductory chapter on " the formation of red blood cells, their life span and destruction; synthesis and katabolism of haemo- globin; and the metabolism of erythrocytes."This is a lot of ground to cover in 36 pages.Much of it is far from clear, and much of it unrelated to paediatric problems.There follows a set of detailed tables showing normal blood values in the neonatal period, prematurity, infancy, and childhood.This section is written by Stransky, who works in the Philippines and draws much of his informa- tion from studies of local children.It is doubtful how far these values are generally applicable, since he states that the majority of Philippine mothers have malnutrition.He also gives figures from workers in other parts of the world, and, while the variability is impressive, it would be helpful if we knew what the author thought about them.For- tunately he reprints towards the end of the chapter a table based on a study of children in Birmingham, England, which-gives a clear idea of the variation of blood values with growth.
Stephen E Malawista
Authors: L. Newman
Journal: BMJ (2013)

Rheumatologist whose work led to the discovery and treatment of Lyme disease

Stephen Malawista is remembered for identifying Lyme disease with his fellow researcher, Alan Steere. Lyme, Old Lyme, and East Haddam, in the eastern part of Connecticut, were at the centre of the first cluster of cases. The condition was initially known as “Lyme arthritis,” but Malawista later termed it “Lyme disease” because of its variable presentation. Both terms drew the ire of people in the area who worried that the value of their property would decline. 

Through meticulous epidemiological and laboratory research, Malawista and Steere learnt that the disease stemmed from a pathogen transmitted by ticks. It was a shift in thinking: it had been thought that Lyme disease was caused by a virus. In 1977 they published the landmark paper that identified Lyme disease as a …
A Controlled Experimental Study of the Therapist-Administrator Split
Authors: JAMES C. BECK, LEE B. MACHT, DANIEL J. LEVINSON, MILTON STRAUSS
Journal: American Journal of Psychiatry (1967)

The effect of separating therapy and administrative responsibilities was evaluated in a controlled experimental study of 24 patients. The authors found that schizophrenics treated by two physicians (a t/a split) remained in the hospital an average of three times as long as schizophrenics treated by one physician, who served as both therapist and administrator. Although the t/a split arrangement appeared to have learning value for the residents who participated, and although there may be specific clinical indications for its use in some cases, the authors conclude that it has no routine place in the treatment of schizophrenic patients.
Effective control of dengue vectors with curtains and water container covers treated with insecticide in Mexico and Venezuela: cluster randomised trials
Authors: Axel Kroeger, Audrey Lenhart, Manuel Ochoa, Elci Villegas, Michael Levy, Neal Alexander, P J McCall
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objectives</b> To measure the impact on the dengue vector population (<i>Aedes aegypti</i>) and disease transmission of window curtains and water container covers treated with insecticide. <b>Design</b> Cluster randomised controlled trial based on entomological surveys and, for Trujillo only, serological survey. In addition, each site had a non-randomised external control. <b>Setting</b> 18 urban sectors in Veracruz (Mexico) and 18 in Trujillo (Venezuela). <b>Participants</b> 4743 inhabitants (1095 houses) in Veracruz and 5306 inhabitants (1122 houses) in Trujillo. <b>Intervention</b> Sectors were paired according to entomological indices, and one sector in each pair was randomly allocated to receive treatment. In Veracruz, the intervention comprised curtains treated with lambdacyhalothrin and water treatment with pyriproxyfen chips (an insect growth regulator). In Trujillo, the intervention comprised curtains treated with longlasting deltamethrin (PermaNet) plus water jar covers of the same material. Follow-up surveys were conducted at intervals, with the final survey after 12 months in Veracruz and nine months in Trujillo. <b>Main outcome measures</b> Reduction in entomological indices, specifically the Breteau and house indices. <b>Results</b> In both study sites, indices at the end of the trial were significantly lower than those at baseline, though with no significant differences between control and intervention arms. The mean Breteau index dropped from 60% (intervention clusters) and 113% (control) to 7% (intervention) and 12% (control) in Veracruz and from 38% to 11% (intervention) and from 34% to 17% (control) in Trujillo. The pupae per person and container indices showed similar patterns. In contrast, in nearby communities not in the trial the entomological indices followed the rainfall pattern. The intervention reduced mosquito populations in neighbouring control clusters (spill-over effect); and houses closer to treated houses were less likely to have infestations than those further away. This created a community effect whereby mosquito numbers were reduced throughout the study site. The observed effects were probably associated with the use of materials treated with insecticide at both sites because in Veracruz, people did not accept and use the pyriproxyfen chips. <b>Conclusion</b> Window curtains and domestic water container covers treated with insecticide can reduce densities of dengue vectors to low levels and potentially affect dengue transmission.
FURTHER EXPERIENCES WITH HALOGENATED SALICYLANILIDES.
Authors: D. S. WILKINSON
Journal: British Journal of Dermatology (1962)

Journal Article FURTHER EXPERIENCES WITH HALOGENATED SALICYLANILIDES. Get access D. S. WILKINSON D. S. WILKINSON Royal Buckinghamshire Hospital, Aylesbury, Bucks Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 74, Issue 8-9, 1 August 1962, Pages 295–301, https://doi.org/10.1111/j.1365-2133.1962.tb13514.x Published: 01 August 1962
More on Attachment Behavior: T'was the Night Before Changeover
Authors: J. Trig Brown
Journal: JAMA (1986)

<h3>To the Editor.—</h3> One model of the physician-patient relationship, attachment theory, is nicely described in Dr Berlin's recent article.<sup>1</sup>He applies this model to explain clinical phenomena observed when the bond between the physician and the patient is disrupted. We encourage him to put his theory to the test. Recently, we and others,<sup>2-4</sup>also prompted by clinical observations, have tried to measure the effect of dissolving the physician-patient relationship in ambulatory medicine clinics. No measurable effect was seen. This does not necessarily mean that dissolving the relationship has no effect; it is possible that the wrong patient behaviors were measured. It may mean, however, that the majority of patients tolerate the termination and transfer of care well. Dr Berlin's experience may be biased because he is called in to consult about those patients who tolerate the termination poorly. It would be a major addition to the understanding of
Relaxation to transmural nerve stimulation and exogenously added norepinephrine in porcine cerebral vessels. A study utilizing cerebrovascular intrinsic tone.
Authors: R J Winquist, R C Webb, D F Bohr
Journal: Circulation Research (1982)

The large arteries at the base of the brain in the pig were studied in vitro for their responsiveness to neurogenic and humoral stimuli. Helical strips of these cerebral vessels tonically contracted consistently following application of resting force. The development and maintenance of this tone were not influenced by prior treatment of strips with tetrodotoxin (5 x 10(-7) M), 6-hydroxydopamine (300 micrograms/ml) guanethidine (5 x 10(-6) M), or antagonists of known vasoactive autacoids (i.e., phentolamine, propranolol, atropine). Once tone reached an equilibrated plateau, transmural nerve stimulation and exogenously applied norepinephrine evoked a relaxation. The relative potency of beta-adrenergic agonists in producing a relaxation was isoproterenol greater than norepinephrine greater than epinephrine much greater than terbutaline. The response to norepinephrine, but not that to transmural nerve stimulation, was abolished by beta-adrenoceptor antagonists. The neurogenic response, but not the relaxation to exogenous catecholamines, was blocked by tetrodotoxin and 6-hydroxydopamine and diminished by guanethidine. Vasoactive intestinal polypeptide and adenosine were also potent relaxant agents. These responses, but not the response to transmural nerve stimulation were blocked by alpha-chymotrypsin (1.5 U/ml) and aminophylline (3 x 10(-5) M), respectively. These results suggest that porcine cerebral vessels develop myogenic tone which allows one to examine neural and/or humoral dilator responses without prior spasmogen addition. The vascular beta-receptors appear to be of the beta 1-subtype which is consistent with that found in other species. The nature of the dilator neurotransmitter is unknown, but the functional integrity of the adrenergic nerve terminals appears important for the neurogenic relaxation.
Chronic anovulation may increase postmenopausal breast cancer risk
Authors: Elizabeth Rasche González
Journal: JAMA (1983)

The suspicion that chronic anovulation with unopposed estrogen production increases a woman's risk of developing breast cancer has now been confirmed—<i>in part</i>—by a large-scale, retrospective epidemiologic study. Such a patient is not at increased risk for<i>pre</i>menopausal carcinoma of the breast, but is at significantly increased risk for postmenopausal carcinoma. For that reason, proposes Carolyn B. Coulam, MD, of the Mayo Clinic, Rochester, Minn, young women with chronic anovulation syndrome should be treated early and older women with a history of premenopausal anovulation should be apprised of their statistically increased risk of developing breast cancer. Coulam, a consultant at the Mayo Clinic and director of its Reproductive Endocrinology and Infertility Clinic, reported her findings at the recent clinical congress of the American College of Surgeons (ACS) in Chicago. In the study, she and colleague John F. Annegers, PhD, currently affiliated with the University of Texas Medical School
METHODS AND EFFECTS OF INCREASING THE URINARY CONSTITUENTS IN THE BODY
Authors: F. W. Hartman
Journal: The Journal of Experimental Medicine (1933)

1. Five methods for the production of slow continued reabsorbtion of urine in the experimental animal are presented. 2. The effects of this prolonged reabsorption of urinary constituents on the blood chemistry and tissues are shown with special reference to the kidney. 3. Large and rapid increase of urinary constituents in the body is definitely destructive to the kidney. 4. The degenerative changes found in the experimental animal in the protected pole of the kidney showing nephritis produced by x-ray and in man in the unscarred portions of the kidney showing chronic nephritis account for the progressive nature and final renal insufficiency of these conditions and are best ascribed to the high levels of excretory products in the body.