tbuckley/cabot-search huggingface dataset:
267Direct contact between human cardiac fibroblasts and human induced pluripotent stem cell-derived cardiomyocytes counteracts changes in calcium cycling induced by soluble mediators
Authors: C Kane, P Dias, N Helen, T Trantidou, P Camelliti, J Gorelik, C M Terracciano
Journal: Cardiovascular Research (2014)

Cardiac fibroblasts influence cardiomyocyte structure and function through direct physical interaction and/or by the secretion of soluble factors. A role for cardiac fibroblasts in cardiomyopathies has been proposed but clear mechanisms are still lacking. This in vitro study set out to characterise the influence of cardiac fibroblasts from patients with dilated cardiomyopathy on cardiomyocyte Ca2+ cycling, a fundamental mechanism of cardiac function universally altered in cardiac disease. Human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) were cultured with human DCM ventricular fibroblasts at a ratio of 2:1 (120,000 fibroblasts to 60,000 iPS-CMs) for 24 hours in three groups: iPS-CMs with fibroblast conditioned medium, co-cultured in transwells to allow bi-directional paracrine communication but prevent physical contact, and iPS-CMs in direct contact with fibroblasts. iPS-CMs alone were used as a baseline. iPS-CMs were field-stimulated at 1Hz and calcium transients were recorded optically. TGF-β, a cytokine previously shown to be important in fibroblast-myocyte interaction, was measured in culture supernate using an ELISA assay. Versus iPS-CMs alone, Ca2+ transient amplitude was reduced in the conditioned medium group but increased in co-culture (p<0.001, F/F0= 4.02±0.07, 3.01±0.03, 4.50±0.07, n= 264, 344 and 306 cells respectively). Time to peak was increased in conditioned medium vs. baseline (p<0.001, 296±5 ms vs. 255.6±3 ms) while reduced in co-culture and further reduced in direct contact (226±3 ms and 195±2 ms respectively, p<0.001). Conditioned medium and co-culture had no effect on time to 80% decay, but direct contact was significantly reduced (p<0.001 vs. baseline, 408±3 ms and 322±2 ms respectively). TGF- β concentration was higher in co-culture supernatant than conditioned medium (210.2 pg/ml vs. 183.7 pg/ml) and reduced in direct contact (137.7 pg/ml). Ventricular fibroblasts from cardiomyopathy patients influence iPS-CM calcium handling properties and the context of this interaction is important in determining the end effects. Effects of soluble mediators are prevented/reversed by culturing fibroblasts in direct contact with cardiac myocytes. Changes in concentration of TGF-β in culture supernates suggest interaction between these cell populations modulates their paracrine activity. Whether this interaction is mediated through physical intercellular connections, mechanical stretch or other paracrine factors is unclear. Further work is needed to identify possible mechanisms and explore the consequences of this interaction in vivo.
Therapy not effective against all cancers in patients with HIV
Authors: X. Bosch
Journal: BMJ (2000)

A collaborative study on the incidence of cancer in adults infected with HIV has shown clear reductions in the incidence of Kaposi's sarcoma and non-Hodgkin's lymphoma since the introduction and widespread use of highly active antiretroviral therapy.

No significant decline has been seen, however, in the incidence of 22 other cancer types or sites, including those of cervical cancer, anal cancer, and Hodgkin's disease.

The results “are reassuring for HIV-infected subjects and do not, at this stage, support the view that cancer incidence rates might increase as HIV-infected people survive longer,” said investigators of the International Collaboration on HIV and Cancer ( Journal of the National …
Mesodermal mesenchymal cells give rise to myofibroblasts, but not epithelial cells, in mouse liver injury
Authors: Ingrid Lua, David James, Jiaohong Wang, Kasper S. Wang, Kinji Asahina
Journal: Hepatology (2014)

Hepatic stellate cells (HSCs) and portal fibroblasts (PFs) are believed to be the major source of myofibroblasts that participate in fibrogenesis by way of synthesis of proinflammatory cytokines and extracellular matrices. Previous lineage tracing studies using MesP1Cre and Rosa26lacZflox mice demonstrated that MesP1+ mesoderm gives rise to mesothelial cells (MCs), which differentiate into HSCs and PFs during liver development. In contrast, several in vivo and in vitro studies reported that HSCs can differentiate into other cell types, including hepatocytes, cholangiocytes, and progenitor cell types known as oval cells, thereby acting as stem cells in the liver. To test whether HSCs give rise to epithelial cells in adult liver, we determined the hepatic lineages of HSCs and PFs using MesP1Cre and Rosa26mTmGflox mice. Genetic cell lineage tracing revealed that the MesP1+ mesoderm gives rise to MCs, HSCs, and PFs, but not to hepatocytes or cholangiocytes, in the adult liver. Upon carbon tetrachloride injection or bile duct ligation surgery-mediated liver injury, mesodermal mesenchymal cells, including HSCs and PFs, differentiate into myofibroblasts but not into hepatocytes or cholangiocytes. Furthermore, differentiation of the mesodermal mesenchymal cells into oval cells was not observed. These results indicate that HSCs are not sufficiently multipotent to produce hepatocytes, cholangiocytes, or oval cells by way of mesenchymal-epithelial transition in vivo. Conclusion: Cell lineage tracing demonstrated that mesodermal mesenchymal cells including HSCs are the major source of myofibroblasts but do not differentiate into epithelial cell types such as hepatocytes, cholangiocytes, and oval cells. (Hepatology 2014;60:311–322)
Decreased Levothyroxine Requirement in Women with Hypothyroidism during Androgen Therapy for Breast Cancer
Authors: Baha M. Arafah
Journal: Annals of Internal Medicine (1994)

Objective: To determine the effects of androgen administration on measures of thyroid function and thyroid hormone replacement doses in women with breast cancer. Design: Consecutive patients with metastatic, hormone-dependent breast cancer who were eligible for androgen treatment. Interventions: Androgen therapy (fluoxymesterone, 10 mg orally twice daily) was continued for as long as it was effective in controlling tumor growth. Patients: 7 patients with no known thyroid disease and 4 others receiving long-term treatment for hypothyroidism. Measurements: Serum levels of total and free thyroxine (T4), thyroid-stimulating hormone (TSH), and T4-binding globulin were determined before and every 4 weeks after androgen therapy was initiated. Results: Within 4 weeks of androgen administration to the seven patients without thyroid disease, serum levels of total T4 and T4-binding globulin decreased (P < 0.001), whereas the calculated free thyroxine index and measured free hormone levels remained unchanged. Six to 12 weeks after androgen therapy was discontinued, all seven patients remained clinically euthyroid, and serum levels returned to baseline values. In contrast, clinical hyperthyroidism developed shortly after androgen was administered to four patients who received long-term thyroid hormone replacement therapy. Within 4 weeks of treatment, the serum free T4 level increased in each of the four patients, whereas the TSH level decreased. Thyroid hormone doses had to be reduced by 25% to 50% to maintain euthyroidism. Conclusions: The study documents the reversible effects of androgens on thyroid hormone levels and indicates the need to reduce thyroid replacement doses in women during androgen therapy. Monitoring thyroid hormone levels in patients receiving replacement therapy and perhaps in those with autonomous thyroid function is necessary after androgen therapy.
More on vitamin C deficiency in mice and humans
Authors: Liang Shen
Journal: Hepatology (2011)

I read with great interest the article by Park etal.,1 who found that a vitamin C deficiency ameliorated liver fibrosis via the up-regulated expression of peroxisome proliferator-activated receptor gamma in senescence marker protein 30 (SMP30) knockout mice. The results are interesting and shed light on the possible mechanisms underlying the attenuated liver fibrosis of SMP30 knockout mice. Here I propose that if these results in SMP30 knockout mice are to be extended to humans, we will need more comprehensive studies based on the new and significant finding that humans employ a unique strategy for adapting to vitamin C deficiency. As we know, humans and some other mammals such as guinea pigs and fruit bats have an inborn metabolic error, that is, an inability to synthesize vitamin C from glucose due to a defective form of the gene for the L-gulonolactone oxidase enzyme required in the last step of vitamin C synthesis.2 Montel-Hagen etal.3 recently demonstrated that human erythrocytes from the vitamin C auxotrophs can dramatically enhance their vitamin C–transporting ability by switching the preference of glucose transporter 1 (Glut1) from glucose to the oxidized form of ascorbic acid [L-dehydroascorbic acid (DHA)]. The membrane protein stomatin has been shown to regulate the substrate preference switch. More interestingly, erythrocyte Glut1 and its associated DHA uptake are specific to species unable to produce vitamin C from glucose. Mice can synthesize vitamin C, and further experimentation has indicated that their mature erythrocytes do not harbor Glut1 or transport DHA. Therefore, in comparison with mice, humans possess a compensatory mechanism to adapt to a vitamin C deficiency, and this may lead us to reevaluate the human vitamin C deficiency status and potentially result in more complicated reflections on vitamin C deficiency in human liver tissues. I do not mean to question the rationality and significance of the findings of Park etal.,1 but Isubmit that this unique compensatory mechanism should be considered in future studies on the relationships between vitamin C deficiency and liver fibrosis in humans. Liang Shen Ph.D.*, * Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Shandong University of Technology, Zibo, People's Republic of China.
Cross-infection by Pseudomonas aeruginosa as a hazard of intensive surgery.
Authors: J E Tinne, A M Gordon, W H Bain, W A Mackey
Journal: BMJ (1967)

Although cross-infection has always presented serious problems, there has within recent years been an increased awareness of the growing prevalence of Gram-negative organisms, especially Pseudomonas aeruginosa, as causes of serious morbidity in the hospital environment (Finland et al., 1959; Williams et al., 1960; Barber, 1961).A variety of factors appear to have contributed to this changing pattern of hospital-acquired bacterial infections, but the extensive use of broad-spectrum antibiotics, corticosteroids, and cytotoxic and immunosuppressive drugs, and the increased susceptibility of individuals subiected to advanced and intensive surgery or medical techniques, have been of major significance.In this context, infections by Ps. aeruginosa, an organism of low pathogenicity to healthy individuals, are likely to be particularly serious and associated with a high mortality.This opportunist has an inherently high resistance to most currently available antibiotics, and many antiseptics are less active against Ps.aeruginosa than against other vegetative bacteria.Recently a series of Ps. aeruginosa infections of the respira- tory tract occurred in a cardiovascular surgical unit involving seven patients, three of whom died.The three fatal cases had been subjected to open-heart surgery followed by intensive care, including tracheostomies and prolonged postoperative mechan- ical ventilation.They had also received corticosteroids, while all the cases had had prophylactic broad-spectrum antibiotic cover.This paper describes the clinical and bacteriological features of the outbreak together with the epidemiological investigations and control measures which were undertaken.
Sympathetic reflex control of skeletal muscle blood flow in patients with congestive heart failure: evidence for beta-adrenergic circulatory control.
Authors: E Kassis, T N Jacobsen, F Mogensen, O Amtorp
Journal: Circulation (1986)

Mechanisms controlling forearm muscle vascular resistance (FMVR) during postural changes were investigated in seven patients with severe congestive heart failure (CHF) and in seven control subjects with unimpaired left ventricular function. Relative brachioradial muscle blood flow was determined by the local 133Xe-washout technique. Unloading of baroreceptors with use of 45 degree upright tilt was comparably obtained in the patients with CHF and control subjects. Control subjects had substantially increased FMVR and heart rate to maintain arterial pressure whereas patients with CHF had decreased FMVR by 51 +/- 11% (mean +/- SEM, p less than .02) and had no increase in heart rate despite a fall in arterial pressure during upright tilt. The autoregulatory and local vasoconstrictor reflex responsiveness during postural changes in forearm vascular pressures were intact in both groups. Further investigations were carried out in the patients with CHF. The left axillary nerve plexus was blocked by local anesthesia in the seven patients. No alterations in forearm vascular pressures were observed. This blockade preserved the local regulation of FMVR but reversed the vasodilator response to upright tilt as FMVR increased by 30 +/- 7% (p less than .02). Blockade of central neural impulses to this limb combined with brachial arterial infusions of phentolamine completely abolished the humoral vasoconstriction in the tilted position. Infusions of propranolol to the contralateral brachial artery that did not affect baseline values of heart rate, arterial pressure, or the local reflex regulation of FMVR reversed the abnormal vasodilator response to upright tilt as FMVR increased by 42 +/- 12% (p less than .02). Despite augmented baseline values, forearm venous but not arterial plasma levels of epinephrine increased in the tilted position, as did arterial rather than venous plasma concentrations of norepinephrine in these patients. The results suggest a beta-adrenergic reflex mechanism elicited by spinal or supraspinal neural impulses and probably modulating a cotransmitter release in the patients with CHF.
Salt Wasting — Consequence of Functional Adaptation?
Authors: Jerome P. Kassirer, F. John Gennari
Journal: New England Journal of Medicine (1977)

It has always seemed remarkable that most patients with severe impairment of kidney function maintain normal sodium balance even though the amount of sodium filtered by their kidneys is reduced to a tiny fraction of normal. It is true that patients with renal disease usually lose abnormal amounts of sodium in their urine when salt intake is severely restricted and retain sodium when salt loaded; yet in most such patients sodium excretion keeps pace with intake despite fairly wide dietary fluctuations. To maintain salt balance when intake is normal and glomerular filtration rate is markedly reduced, patients with renal failure . . .
1003-88 Impact of angioplasty with distal protection device on myocardial reperfusion
Authors: Mamoru Nanasato, Haruo Hirayama, Takashi Muramatsu, Kazumasa Unno, Masayuki Shimano, Kunihiro Matsushita, Hiroto Takezawa, Mitsuhiro Yokota, Toyoaki Murohara
Journal: Journal of the American College of Cardiology (2004)
DNA Methylation Analysis in Nonalcoholic Fatty Liver Disease Suggests Distinct Disease-Specific and Remodeling Signatures after Bariatric Surgery
Authors: Markus Ahrens, Ole Ammerpohl, Witigo von Schönfels, Julia Kolarova, Susanne Bens, Timo Itzel, Andreas Teufel, Alexander Herrmann, Mario Brosch, Holger Hinrichsen, Wiebke Erhart, Jan Egberts, Bence Sipos, Stefan Schreiber, Robert Häsler, Felix Stickel, Thomas Becker, Michael Krawczak, Christoph Röcken, Reiner Siebert, Clemens Schafmayer, Jochen Hampe
Journal: Cell Metabolism (2013)
"Streaming" in Portal Vein
Authors: ANIL G. DESAI, CHAN H. PARK, JOHN F. SCHILLING
Journal: Clinical Nuclear Medicine (1985)

Fifty-five consecutive patients with colorectal carcinoma and hepatic metastases on the Tc-99m sulfur colloid liver/spleen scan (TSC) were evaluated to see if the pattern of spread of colorectal metastases was affected by the venous drainage of the primary site. The results suggest that significant streaming probably exists in the portal vein and the spread of metastases to the liver is affected by it. This information has a potential clinical implication in terms of diagnostic workup and chemotherapeutic infusions. It also supports the speculation that a streaming effect exists in humans.
The divergent domains of the NEFA and nucleobindin proteins are derived from an EF-hand ancestor
Authors: A. Karabinos, D. Bhattacharya, C. Morys-Wortmann, K. Kroll, G. Hirschfeld, H. D. Kratzin, S. Barnikol-Watanabe, N. Hilschmann
Journal: Molecular Biology and Evolution (1996)

The human protein NEFA (DNA binding, EF-hand, Acidic region) has previously been isolated from a KM3 cell line and immunolocalized on the plasma membrane, in the cytoplasma, and in the culture medium. Sequence analysis of a cDNA clone encoding NEFA identified a hydrophilic domain, two EF-hands, and a leucine zipper at the C-terminus. These characters are shared with nucleobindin (Nuc). In this paper we have further characterized NEFA and probed its evolutionary origins. Circular dichroism (CD) spectra of recombinant NEFA indicated a helical content of 51% and showed that the EF-hands are capable of binding Ca2+. Experiments with recombinant NEFA and synthesized peptides revealed that the leucine zipper cannot form a homodimer. The leucine zipper may allow heterodimer formation of NEFA and an unknown protein. Phylogenetic analyses suggest that this protein is derived from a four-domain EF-hand ancestor with subsequent duplications and fusions. The leucine zipper and putative DNA-binding domains of NEFA have evolved secondarily from existing EF-hand sequences. These analyses provide insights into how complex proteins may originate and trace the precursor of NEFA to the common ancestor of eukaryotes.
Hypoxia induces severe right ventricular dilatation and infarction in heme oxygenase-1 null mice
Authors: Shaw-Fang Yet, Mark A. Perrella, Matthew D. Layne, Chung-Ming Hsieh, Koji Maemura, Lester Kobzik, Philippe Wiesel, Helen Christou, Stella Kourembanas, Mu-En Lee
Journal: Journal of Clinical Investigation (1999)

Heme oxygenase (HO) catalyzes the oxidation of heme to generate carbon monoxide (CO) and bilirubin. CO increases cellular levels of cGMP, which regulates vascular tone and smooth muscle development. Bilirubin is a potent antioxidant. Hypoxia increases expression of the inducible HO isoform (HO-1) but not the constitutive isoform (HO-2). To determine whether HO-1 affects cellular adaptation to chronic hypoxia in vivo, we generated HO-1 null (HO-1–/–) mice and subjected them to hypoxia (10% oxygen) for five to seven weeks. Hypoxia caused similar increases in right ventricular systolic pressure in wild-type and HO-1–/– mice. Although ventricular weight increased in wild-type mice, the increase was greater in HO-1–/– mice. Similarly, the right ventricles were more dilated in HO-1–/– mice. After seven weeks of hypoxia, only HO-1–/– mice developed right ventricular infarcts with organized mural thrombi. No left ventricular infarcts were observed. Lipid peroxidation and oxidative damage occurred in right ventricular cardiomyocytes in HO-1–/–, but not wild-type, mice. We also detected apoptotic cardiomyocytes surrounding areas of infarcted myocardium by terminal deoxynucleotide transferase–mediated dUTP nick end-labeling (TUNEL) assays. Our data suggest that in the absence of HO-1, cardiomyocytes have a maladaptive response to hypoxia and subsequent pulmonary hypertension.
Primary Immunodeficiency Diseases in Adults
Authors: Scott H. Sicherer
Journal: JAMA (1998)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract LB-327: Inhibition of lymphatic metastasis in neuroblastoma by a novel neutralizing antibody to vascular endothelial growth factor-D.
Authors: Kenji Kashima, Miho Watanabe, Yasuko Satoh, Junichi Hata, Nobuya Ishii, Yuko Aoki
Journal: Cancer Research (2013)

Abstract Lymphatic spread is an important clinical determinant in the prognosis of many human cancers. The lymphangiogenic factor called vascular endothelial growth factor-D (VEGF-D) is implicated in the promotion of lymphatic metastasis through the development of lymphatic vessels in some human cancers. In this study, we developed an anti-VEGF-D monoclonal antibody, cVE199, and investigated its in vitro properties, in vivo effects against tumors, and possible target indications to evaluate its potential as a therapeutic antibody. The cVE199 molecule was revealed to have a specific binding reactivity against human VEGF-D, as well as a specific inhibitory activity against the binding of human VEGF-D to VEGFR-3. In addition, cVE199 was found to inhibit the biological activity of VEGF-D against lymphatic cells in vitro. Because we determined that a neuroblastoma cell line, SK-N-DZ, abundantly expressed VEGF-D, an in vivo efficacy study was performed using a xenograft model of SK-N-DZ. We found that cVE199 significantly decreased lymphatic metastasis of SK-N-DZ as well as lymphangiogenesis in primary lesions. Finally, we investigated VEGF-D expression in human neuroblastoma, finding that the molecule was expressed in 11 of 29 human neuroblastoma specimens (37.9%). In conclusion, we found that a novel anti-VEGF-D monoclonal antibody, cVE199, with specific reactivity against human VEGF-D prevents lymphatic metastasis of neuroblastoma through the inhibition of lymphangiogenesis in an animal model. In addition, our results show that VEGF-D is expressed in some cases of human neuroblastomas, which suggests that cVE199 is a potential anti-metastasis therapeutic antibody in neuroblastoma treatment. Citation Format: Kenji Kashima, Miho Watanabe, Yasuko Satoh, Junichi Hata, Nobuya Ishii, Yuko Aoki. Inhibition of lymphatic metastasis in neuroblastoma by a novel neutralizing antibody to vascular endothelial growth factor-D. [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 LB-327. doi:10.1158/1538-7445.AM2013-LB-327
Not all patients with displaced proximal humerus fractures are suitable for sling treatment
Authors: Kanthan Theivendran, Sami Hassan, Amol Tambe, Tim Cresswell, David I Clark
Journal: BMJ (2015)

We commend the PROFHER Randomised Clinical Trial collaborators and the patients involved in the landmark study reported by Wise in news.1 It is rare to complete such a large randomised trial of surgery, let alone surgery on patients with trauma.

However, we would like to draw attention …