tbuckley/cabot-search huggingface dataset:
l-Ascorbic acid 2-phosphate promotes elongation of hair shafts via the secretion of insulin-like growth factor-1 from dermal papilla cells through phosphatidylinositol 3-kinase
Authors: M.H. Kwack, S.H. Shin, S.R. Kim, S.U. Im, I.S. Han, M.K. Kim, J.C. Kim, Y.K. Sung
Journal: British Journal of Dermatology (2009)

l-Ascorbic acid 2-phosphate (Asc 2-P), a derivative of l-ascorbic acid, promotes elongation of hair shafts in cultured human hair follicles and induces hair growth in mice.To investigate whether the promotion of hair growth by Asc 2-P is mediated by insulin-like growth factor-1 (IGF-1) and, if so, to investigate the mechanism of the Asc 2-P-induced IGF-1 expression.Dermal papilla (DP) cells were cultured and IGF-1 level was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay after Asc 2-P treatment in the absence or presence of LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. Also, hair shaft elongation in cultured human scalp hair follicles and proliferation of cocultured keratinocytes were examined after Asc 2-P treatment in the absence or presence of neutralizing antibody against IGF-1. In addition, keratinocyte proliferation in cultured hair follicles after Asc 2-P treatment in the absence or presence of LY294002 was examined by Ki-67 immunostaining.IGF-1 mRNA in DP cells was upregulated and IGF-1 protein in the conditioned medium of DP cells was significantly increased after treatment with Asc 2-P. Immunohistochemical staining showed that IGF-1 staining is increased in the DP of cultured human hair follicles by Asc 2-P. The neutralizing antibody against IGF-1 significantly suppressed the Asc 2-P-mediated elongation of hair shafts in hair follicle organ culture and significantly attenuated Asc 2-P-induced growth of cocultured keratinocytes. LY294002 significantly attenuated Asc 2-P-inducible IGF-1 expression and proliferation of follicular keratinocytes in cultured hair follicles.These data show that Asc 2-P-inducible IGF-1 from DP cells promotes proliferation of follicular keratinocytes and stimulates hair follicle growth in vitro via PI3K.
The Enhanced Myocardial Contractility of Thyrotoxicosis
Authors: WILLIAM GROSSMAN
Journal: Annals of Internal Medicine (1971)

The role of beta adrenergic influences in maintaining the enhanced myocardial contractility of thyrotoxicosis was studied in 10 hyperthyroid patients, using sotalol, a beta adrenergic blocking agent free of intrinsic myocardial depressant properties. The isovolumic contraction period, corrected ejection time, and the ratio of the pre-ejection period to the left ventricular ejection time were used as indexes of myocardial contractility and showed no significant change after beta receptor blockade with sotalol. Heart rate decreased (109 ± 6 beats/min to 83 ± 5 beats/min or -24%; P < 0.01), pulse pressure decreased (89 ± 14 mm Hg to 73 ± 10 mm Hg or -17%; P < 0.02), and circulation time (hand to tongue) increased (14.5 ± 1.5 sec to 17.3 ± 1.8 sec or +9%; P < 0.05) after beta blockade. No significant changes occurred in oxygen consumption, skin temperature, respiratory rate, or serum thyroxine. Although the tachycardia, shortened circulation time, and widened pulse pressure of thyrotoxicosis are apparently mediated by beta adrenergic influences, the heightened ventricular function associated with thyrotoxicosis seems to be independent of beta adrenergic influences and probably represents a primary effect of thyroxine on the heart.
Hormone Replacement Therapy and Increased Plasma Concentration of C-Reactive Protein
Authors: Paul M. Ridker, Charles H. Hennekens, Nader Rifai, Julie E. Buring, JoAnn E. Manson
Journal: Circulation (1999)

Background —It has been hypothesized that postmenopausal hormone replacement therapy (HRT) may increase levels of C-reactive protein (CRP), a marker of inflammation associated with increased risk of future cardiovascular events. However, data evaluating this hypothesis are sparse and limited to older women. Methods and Results —CRP levels were evaluated in a cross-sectional survey of 493 healthy postmenopausal women; mean age was 51 years. Overall, median CRP levels were 2 times higher among women taking HRT than among women not taking HRT (0.27 versus 0.14 mg/dL; P =0.001). This difference was present in all subgroups evaluated, including those with no history of hypertension, hyperlipidemia, obesity, diabetes, or cigarette consumption or a family history of premature coronary artery disease (all P &lt; 0.01). Compared with nonusers of HRT, median CRP levels were higher among women using estrogen alone ( P =0.003) and women using estrogen plus progesterone ( P =0.03); however, there was no significant difference in CRP levels between users of different HRT preparations. In multivariate analysis, the relationship between HRT use and CRP remained significant after control for body mass index, age, diabetes, hypertension, hyperlipidemia, alcohol use, and cigarette consumption ( P =0.001). Conclusions —In this cross-sectional survey, CRP levels were increased among apparently healthy postmenopausal women taking HRT. The potential impact of HRT on inflammatory parameters should be investigated in ongoing clinical trials.
Drug Abuse in Anesthesia Training Programs
Authors: C. F. Ward
Journal: JAMA (1983)

Experience at our institution with drug dependence among anesthesia residents, coupled with a lack of published data, prompted us to survey US anesthesia training programs. Two hundred eighty-nine programs were surveyed, 247 (85.5%) responded, and 184 (74%) of these programs had at least one suspected incident of drug dependence to report. Three hundred thirty-four confirmed persons were reported, including a substantial number of instructors. Meperidine and fentanyl were the most frequently mentioned drugs. Behavior changes were frequently noted by staff personnel, and in general such changes led directly to detection. After confirmation of abuse, the majority of impaired anesthetists were referred for psychiatric care, with few in need of actual detoxification. Detailed follow-up was available for about 40% of the total; 71 persons were offered a return to their original place of employment, while 30 persons died of drug overdose. Chemical impairment may be more common than usually thought in anesthesia, perhaps in part because of drug availability. (<i>JAMA</i>1983;250:922-925)
Photosensitizer-Conjugated Human Serum Albumin Nanoparticles for Effective Photodynamic Therapy
Authors: Hayoung Jeong, MyungSook Huh, So Jin Lee, Heebeom Koo, Ick Chan Kwon, Seo Young Jeong, Kwangmeyung Kim
Journal: Theranostics (2011)

Photodynamic therapy (PDT) is an emerging theranostic modality for various cancers and diseases. The focus of this study was the development of tumor-targeting albumin nanoparticles containing photosensitizers for efficient PDT. To produce tumor-targeting albumin nanoparticles, the hydrophobic photosensitizer, chlorin e6 (Ce6), was chemically conjugated to human serum albumin (HSA). The conjugates formed self-assembled nanoparticle structures with an average diameter of 88 nm under aqueous conditions. As expected, the Ce6-conjugated HSA nanoparticles (Ce6-HSA-NPs) were nontoxic in their native state, but upon illumination with the appropriate wavelength of light, they produced singlet oxygen and damaged target tumor cells in a cell culture system. Importantly, when the nanoparticles were injected through the tail vein into tumor-bearing HT-29 mice, Ce6-HSA-NPs compared with free Ce6 revealed enhanced tumor-specific biodistribution and successful therapeutic results following laser irradiation. These results suggest that highly tumor-specific albumin nanoparticles have the potential to serve not only as efficient therapeutic agents, but also as photodynamic imaging (PDI) reagents in cancer treatment.
Current Concepts in Cobalamin Deficiency
Authors: Ralph Carmel
Journal: Annual Review of Medicine (2000)

The application of sensitive metabolic tests, such as the deoxyuridine suppression test and measurement of homocysteine and methylmalonic acid, to cobalamin status has identified the entity of mild, preclinical cobalamin deficiency. This state, common in the elderly, responds to cobalamin therapy. Preclinical deficiency may exist within the nervous system as well, although this requires further study. Nevertheless, it is well to remember that not all low cobalamin levels and not all abnormal metabolite results reflect cobalamin deficiency. Interpretation of metabolic results still requires caution, as do proposals to raise the cut-off point for low cobalamin levels to capture some normal levels that are associated with metabolic abnormality. The recognition of mild, preclinical deficiency has opened up many important issues. These include identifying its causes, what should be done about it, and what the clinical impact of the hyperhomocysteinemia itself is. Although malabsorptive disorders, especially food-cobalamin malabsorption, underlie about half of all cases of preclinical deficiency, no cause can be found in the remainder of these cases; poor dietary intake appears to be uncommon. In addition, unusual states of neurologically symptomatic cobalamin deficiency are being recognized, such as nitrous oxide exposure in patients with unrecognized deficiency and severe deficiency in children of mildly deficient mothers. All of these have broadened and complicated the picture of cobalamin deficiency while providing greater opportunities for prevention.
Phase II Trial of Primary Chemotherapy Followed by Reduced-Dose Radiation for CNS Germ Cell Tumors
Authors: Jan C. Buckner, Prema P. Peethambaram, William A. Smithson, Robert V. Groover, Paula J. Schomberg, David W. Kimmel, Corey Raffel, Judith R. O'Fallon, Joseph Neglia, Edward G. Shaw
Journal: Journal of Clinical Oncology (1999)

PURPOSE: A prospective phase II study was initiated to assess the response rate, survival, and late effects of treatment in patients with newly diagnosed CNS germ cell tumors (GCT), using etoposide plus cisplatin followed by radiation therapy prescribed by extent of disease, histology, and response to chemotherapy. PATIENTS AND METHODS: Seventeen patients aged 8 to 24 years with histologically proven CNS GCT received etoposide (100 mg/m 2 /d) plus cisplatin (20 mg/m 2 /d) daily for 5 days every 3 weeks for four cycles, followed by radiation therapy. Nine patients had germinomas; eight had mixed GCT. Four patients (three with germinomas and one with mixed GCT) presented with leptomeningeal dissemination. RESULTS: Radiographically, 14 of 17 patients were assessable for response; 11 patients experienced complete regression, and three had major partial regression before radiation. Six of seven assessable patients with elevated CSF levels of alpha-fetoprotein or beta–human chorionic gonadotropin had normalization with chemotherapy alone; all normalized with combined chemotherapy and radiation therapy. All 17 patients are alive without evidence of disease (median follow-up, 51 months). One patient developed a relapse in the spinal leptomeninges and was rendered free of disease with spinal radiation more than 5 years ago. One patient developed carotid stenosis requiring surgery. Thus far, only minimal long-term deterioration in neurocognitive function has been detected as a consequence of protocol treatment. CONCLUSION: Conventional-dose intravenous chemotherapy with etoposide and cisplatin can effect tumor regression in a high proportion of patients with CNS GCT, including those with leptomeningeal metastases. Acute and long-term toxicities are acceptable. Progression-free survival and overall survival are excellent.
IGFBP-rP1, a potential molecule associated with colon cancer differentiation
Authors: Wenjing Ruan, Shuzhen Zhu, Haibing Wang, Fangying Xu, Hong Deng, Yu Ma, Maode Lai
Journal: Molecular Cancer (2010)

Abstract Background In our previous studies, we have demonstrated that insulin-like growth factor binding protein-related protein1 (IGFBP-rP1) played its potential tumor suppressor role in colon cancer cells through apoptosis and senescence induction. In this study, we will further uncover the role of IGFBP-rP1 in colon cancer differentiation and a possible mechanism by revealing responsible genes. Results In normal colon epithelium, immunohistochemistry staining detected a gradient IGFBP-rP1 expression along the axis of the crypt. IGFBP-rP1 strongly expressed in the differentiated cells at the surface of the colon epithelium, while weakly expressed at the crypt base. In colon cancer tissues, the expression of IGFBP-rP1 correlated positively with the differentiation status. IGFBP-rP1 strongly expressed in low grade colorectal carcinoma and weakly expressed in high grade colorectal carcinoma. In vitro, transfection of PcDNA3.1(IGFBP-rP1) into RKO, SW620 and CW2 cells induced a more pronounced anterior-posterior polarity morphology, accompanied by upregulation with alkaline phosphatase (AKP) activity. Upregulation of carcino-embryonic antigen (CEA) was also observed in SW620 and CW2 transfectants. The addition of IGFBP-rP1 protein into the medium could mimic most but not all effects of IGFBP-rP1 cDNA transfection. Seventy-eight reproducibly differentially expressed genes were detected in PcDNA3.1(IGFBP-rP1)-RKO transfectants, using Affymetrix 133 plus 2.0 expression chip platform. Directed Acyclic Graph (DAG) of the enriched GO categories demonstrated that differential expression of the enzyme regulator activity genes together with cytoskeleton and actin binding genes were significant. IGFBP-rP1 could upreguate Transgelin (TAGLN), downregulate SRY (sex determining region Y)-box 9(campomelic dysplasia, autosomal sex-reversal) (SOX9), insulin receptor substrate 1(IRS1), cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) (CDKN2B), amphiregulin(schwannoma-derived growth factor) (AREG) and immediate early response 5-like(IER5L) in RKO, SW620 and CW2 colon cancer cells, verified by Real time Reverse Transcription Polymerase Chain Reaction (rtRT-PCR). During sodium butyrate-induced Caco2 cell differentiation, IGFBP-rP1 was upregulated and the expression showed significant correlation with the AKP activity. The downregulation of IRS1 and SOX9 were also induced by sodium butyrate. Conclusion IGFBP-rP1 was a potential key molecule associated with colon cancer differentiation. Downregulation of IRS1 and SOX9 may the possible key downstream genes involved in the process.
Tuberculosis and HIV infection
Authors: T. Jacob John, Amitinder Kaur, P. George Babu, PaulA. Reeve, N. Bevilacqua, G. Marasca, A. Moscati, M. Fantoni, F. Ricci, L. Ortona, JosephL. Malone, ScottF. Paparello, JohnD. Malone, HalE. Hill, JamesW. Myers, Peter Weiss, MilesB. Markus
Journal: The Lancet (1993)
Nitric oxide production and perivascular nitration in brain after carbon monoxide poisoning in the rat.
Authors: H Ischiropoulos, M F Beers, S T Ohnishi, D Fisher, S E Garner, S R Thom
Journal: Journal of Clinical Investigation (1996)

Nitric oxide is a short-lived free radical and physiological mediator which has the potential to cause cytotoxicity. Studies were conducted to investigate whether nitric oxide, and the potent oxidant peroxynitrite, were generated in brain during experimental carbon monoxide (CO) poisoning in the rat. Nitric oxide production was documented by electron paramagnetic resonance spectroscopy, and found to be increased by ninefold immediately after CO poisoning. Evidence that peroxynitrite was generated was sought by looking for nitrotyrosine in the brains of CO-poisoned rats. Nitrotyrosine was found deposited in vascular walls, and also diffusely throughout the parenchyma in inummocytochemical studies. The affinity and specificity of an anti-nitrotyrosine antibody was investigated and a solid phase immunoradiochemical assay was developed to quantity nitrotyrosine in brain homogenates. A 10-fold increase in nitrotyrosine was found in the brains of CO-poisoned rats. Platelets were involved with production of nitrotyrosine in the early phase of exposure to CO. However, nitrotyrosine formation and leukocyte sequestration were not decreased in thrombocytopenic rats poisoned with CO according to the standard model. When rats were pre-treated with the nitric oxide synthase inhibitor, L-nitroarginine methyl ester, formation of both nitric oxide and nitrotyrosine in response to CO poisoning were abolished, as well as leukocyte sequestration in the microvasculature, endothelial xanthine dehydrogenase conversion to xanthine oxidase, and brain lipid peroxidation. We conclude that perivascular reactions mediated by peroxynitrite are important in the cascade of events which lead to brain oxidative stress in CO poisoning.
Where the patient is
Authors: Douglas Kamerow
Journal: BMJ (2007)

The BMJ' s stated mission is to help doctors make better decisions, and sometimes that comes through understanding what patients feel. Our sporadic series called “A patient's journey” offers a voice to patients to help us understand what we can never really know—what it feels like to have a specific disease.

Ray Jobling has had psoriasis for more than 50 years, …
Hyperinsulinemic Hypoglycemia After Gastric Bypass Surgery Is Not Accompanied by Islet Hyperplasia or Increased β-Cell Turnover
Authors: Juris J. Meier, Alexandra E. Butler, Ryan Galasso, Peter C. Butler
Journal: Diabetes Care (2006)

The purpose of this study was to establish whether hypoglycemia after gastric bypass surgery (GBS) for morbid obesity is due to increased fractional beta-cell area or inappropriately increased insulin secretion.We examined pancreata obtained at partial pancreatectomy from 6 patients with post-GBS hypoglycemia and compared these with 31 pancreata from obese subjects and 16 pancreata from lean control subjects obtained at autopsy. We addressed the following questions. In patients with post-GBS hypoglycemia, is beta-cell area increased and is beta-cell formation increased or beta-cell apoptosis decreased?We report that in patients with post-GBS hypoglycemia, beta-cell area was not increased compared with that in obese or even lean control subjects. Consistent with this finding, there was no evidence of increased beta-cell formation (islet neogenesis and beta-cell replication) or decreased beta-cell loss in patients with post-GBS hypoglycemia. In control subjects, mean beta-cell nuclear diameter correlated with BMI (r(2) = 0.79, P < 0.001). In patients with post-GBS hypoglycemia, beta-cell nuclear diameter was increased (P < 0.001) compared with that for BMI in matched control subjects but was appropriate for BMI before surgery.We conclude that post-GBS hypoglycemia is not due to increases in beta-cell mass or formation. Rather, postprandial hypoglycemia after GBS is due to a combination of gastric dumping and inappropriately increased insulin secretion, either as a failure to adaptively decrease insulin secretion after GBS or as an acquired phenomenon.
Utility of Homeostasis Model Assessment of β-Cell Function in Predicting Diabetes in 12,924 Healthy Koreans
Authors: Sun H. Kim, Ki-Chul Sung, Gerald M. Reaven
Journal: Diabetes Care (2010)

We appreciate the thoughtful comments by Boyko (1). The premise of our study (2) was to understand whether homeostasis model assessment (HOMA) of β-cell function (HOMA-β) had utility in predicting diabetes development above and beyond glucose concentration in a large sample of individuals. We concluded that it did not. Even in narrowly defined glucose categories (normal fasting glucose [NFG], <5.6 mmol/l; impaired fasting glucose [IFG]-100, 5.6–6.0 mmol/l; and IFG-110, 6.1–6.9 mmol/l), baseline glucose concentrations …
Using Tandem Mass Spectrometry in Targeted Mode to Identify Activators of Class IA PI3K in Cancer
Authors: Xuemei Yang, Alexa B. Turke, Jie Qi, Youngchul Song, Brent N. Rexer, Todd W. Miller, Pasi A. Jänne, Carlos L. Arteaga, Lewis C. Cantley, Jeffrey A. Engelman, John M. Asara
Journal: Cancer Research (2011)

Phosphatiditylinositide-3-kinase (PI3K) is activated in some cancers by direct mutation, but it is activated more commonly in cancer by mutation of upstream acting receptor tyrosine kinases (TK). At present, there is no systematic method to determine which TK signaling cascades activate PI3K in certain cancers, despite the likely utility of such information to help guide selection of tyrosine kinase inhibitor (TKI) drug strategies for personalized therapy. Here, we present a quantitative liquid chromatography tandem mass spectrometry approach that identifies upstream activators of PI3K both in vitro and in vivo. Using non-small cell lung carcinoma to illustrate this approach, we show a correct identification of the mechanism of PI3K activation in several models, thereby identifying the most appropriate TKI to downregulate PI3K signaling. This approach also determined the molecular mechanisms and adaptors required for PI3K activation following inhibition of the mTOR kinase TORC1. We further validated the approach in breast cancer cells with mutational activation of PIK3CA, where tandem mass spectrometry detected and quantitatively measured the abundance of a helical domain mutant (E545K) of PIK3CA connected to PI3K activation. Overall, our findings establish a mass spectrometric approach to identify functional interactions that govern PI3K regulation in cancer cells. Using this technique to define the pathways that activate PI3K signaling in a given tumor could help inform clinical decision making by helping guide personalized therapeutic strategies for different patients.
The airway vasculature: recent advances and clinical implications
Authors: P Paredi, P J Barnes
Journal: Thorax (2009)

It is increasingly recognised that the airway circulation plays an important role in airway diseases, either through a change in blood flow or through microvascular leakage. Most of the information available regarding the anatomy and physiology of bronchial blood flow and its regulation has necessarily derived from animal studies. However, there have recently been important advances in understanding airway blood flow in airway disease in humans through the development of non-invasive methods and in the quantification of microvascular leakage using plasma markers. These studies have shown that bronchial blood flow is increased in patients with asthma but not in those with chronic obstructive pulmonary disease, confirming previous pathology investigations. Changes in bronchial blood flow may in part reflect the generation of new vascular vessels, a process known as “angiogenesis” which is caused by airway inflammation. Angiogenesis and the resulting plasma leak affect airway physiology, drug clearance and its bioavailability. This review discusses the anatomy, physiology and regulation of bronchial blood flow in the normal and diseased lung, In addition, it analyses the effect of current medical treatment and discusses the potential use of new anti-angiogenesis medications. The development of non-invasive assessment of bronchial blood flow and the study of angiogenesis have provided a tool to investigate airway physiology in vivo; these advances will contribute to a better understanding of inflammatory airway diseases as well as the implication of these findings to management.
Adenocarcinoma in Barrett's oesophagus: an overrated risk.
Authors: A H Van der Veen, J Dees, J D Blankensteijn, M Van Blankenstein
Journal: Gut (1989)

Barrett's oesophagus is a risk factor for the development of oesophageal cancer and for this reason annual endoscopic surveillance has been proposed. In this retrospective study of all patients with Barrett's oesophagus diagnosed in a 12 year period carcinoma had developed in only four patients. The incidence of oesophageal cancer in this series was one in 170 patient years, which means a 30-fold increase compared with the general population. The survival of patients with Barrett's oesophagus was not different, however, from an age and sex matched control population. It is concluded that systematic endoscopic surveillance of patients with Barrett's oesophagus is not indicated.