Huntington Hospital

When two clonal lines of mouse fibroblasts, each containing a drug-resistant marker, are grown together for 4 days, hybrid cells can be detected by selective conditions. These hybrid cells are presumed to be the result of mating. By the same method evidence can be obtained which suggests that mating may be followed by segregation.

BACKGROUND: The extent of serious complications in people who have acquired chronic hepatitis C infection after a blood transfusion is unclear. METHODS: We studied 131 patients with chronic post-transfusion hepatitis C who were referred to our center between February 1980 and June 1994. Eighty-two other patients were excluded because they had multiple transfusions, hemophilia, intravenous drug use, human immunodeficiency virus infection, hepatitis B infection, hemochromatosis, or alcoholic liver disease. Liver biopsies were performed in 101 patients; biopsies were not performed in the other 30 patients, all with signs of cirrhosis, because the results of coagulation tests were abnormal. RESULTS: The mean age of the patients was 57 years (range, 21 to 81) at the time of our initial evaluation. The mean age at the time of the blood transfusion was 35 years (range, 1 to 76). The mean duration of follow-up after presentation to us was 3.9 years (range, 1 to 15). Eighty-eight of the patients (67.2 percent) initially had fatigue, and 89 (67.9 percent) had hepatomegaly. Twenty-seven patients (20.6 percent) initially had chronic hepatitis, 30 (22.9 percent) had chronic active hepatitis, 67 (51.1 percent) had cirrhosis, and 7 (5.3 percent) had hepatocellular carcinoma. Hepatocellular carcinoma developed in an additional seven patients an average of 36 months (range, 7 to 121) after the initial visit. During follow-up, 20 patients (15.3 percent) died: 8 from complications of cirrhosis (1 after a liver transplantation); 11 from hepatocellular carcinoma; and 1, with chronic active hepatitis, from pneumonia. CONCLUSIONS: In a group of patients seen at a referral center, chronic post-transfusion hepatitis C was a progressive disease and, in some patients, led to death from either liver failure or hepatocellular carcinoma.

The cell-free rat liver system in which Cl*-amino acids are incorporated irreversibly into cY-peptide linkage in protein has been used in our laboratories for a number of years as a measure of protein synthesis. The essential components of this system are the microsomal ribonucleoprotein particles, certain enzymes derived from the soluble protein fraction, adenosine triphosphate, guanosine dior triphosphate, and a nucleoside triphosphate-generating system (l-3). The ribonucleoprotein particles of the microsomes appear to be the actual site of peptide condensation. The soluble enzymes and ATP’ have been found to effect the initial carboxyl activation of the amino acids (4). The role of GTP is not yet understood, although the present paper sheds light on its probable locus of action. Much evidence has accumulated in the past 8 years, beginning with the studies of Caspersson (5) and Brachet (6), implicating a role for cellular RNA in protein synthesis. The intermediate stages between amino acid activation and final incorporation into protein in the rat liver in vitro system offered us unexplored regions in which to seek more direct evidence for a chemical association of RNA and amino acids. A preliminary report of such an association has recently been presented by us (7). There it was shown that the RNA of a particular fraction of the cytoplasm hitherto uncharacterized became labeled with Cl*-amino acids in t,he presence of ATP and the amino acid-activating enzymes, and that this labeled RNA subsequently was able to transfer the amino acid to microsomal protein

BACKGROUND: Vancomycin hydrochloride treatment failure for infections caused by susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains with high minimum inhibitory concentration (MIC) has prompted recent guidelines to recommend a higher vancomycin target trough of 15 to 20 microg/mL. METHODS: A prospective cohort study of adult patients infected with MRSA was performed to determine the distribution of vancomycin MIC and treatment outcomes with vancomycin doses targeting an unbound trough of at least 4 times the MIC. The microbiology laboratory computer records were used to identify all patients from whom MRSA was isolated from August 1, 2004, through June 30, 2005. Primary outcome measures were clinical response, mortality, and nephrotoxicity. Patients were placed into subgroups based on target trough attainment and high vs low vancomycin MIC (>/=2 vs <2 microg/mL) for efficacy and high vs low trough (>/=15 vs <15 microg/mL) for nephrotoxicity analyses. RESULTS: Of the 95 patients in the study, 51 (54%) were infected with high-MIC strains and had pneumonia (77%) and/or bacteremia. An initial response rate of 74% was achieved if the target trough was attained irrespective of MIC. However, despite achieving the target trough, the high-MIC group had lower end-of-treatment responses (24/39 [62%] vs 34/40 [85%]; P = .02) and higher infection-related mortality (11/51 [24%] vs 4/44 [10%]; P=.16) compared with the low-MIC group. High MIC (P = .03) and Acute Physiology and Chronic Health Evaluation II score (P = .009) were independent predictors of poor response in multivariate analysis. Nephrotoxicity occurred only in the high-trough group (11/63 [12%]), significantly predicted by concomitant therapy with other nephrotoxic agents. CONCLUSIONS: High prevalence of clinical MRSA strains with elevated vancomycin MIC (2 microg/mL) requires aggressive empirical vancomycin dosing to achieve a trough greater than 15 microg/mL. Combination or alternative therapy should be considered for invasive infections caused by these strains.

Breast cancer is the most common form of cancer in American women across most ethnic groups. Although the psychosocial impact of breast cancer is being studied, there is little information on women from diverse ethnic and socioeconomic backgrounds. We conducted a qualitative study with breast cancer survivors (BCS) of various ethnicities. A total of 102 BCS participated in focus group interviews (24 African Americans, 34 Asians, 26 Latinas and 18 Caucasians); 20 health professionals participated in key informant interviews. Important ethnic differences in type of treatment were noted, Asians and Latinas were more likely to receive mastectomies and African American BCS were least likely to receive adjuvant therapies, including radiation and chemotherapy. These BCS enjoyed a fairly good overall health-related quality of life (HRQOL) with some persistent concerns. The prevailing concerns among all women included overall health, moderate physical concerns, cancer recurrence or metastases, psychosocial concerns related to worry about children and burdening the family, and body image and sexual health concerns. Additional challenges included: lack of knowledge about breast cancer; medical care issues such as insurance, cost and amount of time spent with physician; cultural sensitivity of providers, language barriers, cultural factors related to beliefs about illness, gender role and family obligations (e.g. self-sacrifice). These BCS, particularly the women of color, voiced that their spiritual beliefs and practices are central to their coping. This study accomplishes two goals; it adds to the sparse literature concerning the psychosocial sequelae of breast cancer among women of color, and it increases our knowledge of specific cultural influences (e.g. dietary practices, coping) and socio-ecological factors on HRQOL. More importantly, the study addressed areas that have not been studied before, specifically, an in-depth study on BCS QOL comparing multiple ethnic groups in the US. The results of this investigation will provide preliminary information to survivors and health-care providers about the impact of culture and socio-ecological contexts on survivorship. Among women of all major ethnic groups, breast cancer is the most common form of cancer and the second leading cause of cancer death (American Cancer Society (ACS), 2002). In 2002, over 203,000 women in the United States will be diagnosed with breast cancer (ACS, 2002). Ethnic disparities exist for cancer stage, diagnosis, survival, morbidity and mortality. In general, ethnic minority women are diagnosed with more advanced disease and experience greater morbidity and mortality (Haynes & Smedley, 1999; Miller et al., 1996; Ries et al., 2000; Shinagawa, 2000). In general, increases in survival rates have prompted greater interest in the quality of life (QOL) of breast cancer survivors (BCS) over the past two decades. Additionally, the QOL of cancer survivors from diverse ethnic, cultural and socioeconomic backgrounds is an emerging priority area for studies on survivorship research and clinical care (Haynes and Smedley, 1999; National Cancer Institute (NCI), 2002; President's Cancer Panel, 2000).

PURPOSE: Mammography, the standard method of breast cancer screening, misses many cancers, especially in dense-breasted women. We compared the performance and diagnostic yield of mammography alone versus an automated whole breast ultrasound (AWBU) plus mammography in women with dense breasts and/or at elevated risk of breast cancer. METHODS: AWBU screening was tested in 4,419 women having routine mammography ( TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00649337). Cancers occurring during the study and subsequent 1-year follow-up were evaluated. Sensitivity, specificity and positive predictive value (PPV) of biopsy recommendation for mammography alone, AWBU and mammography with AWBU were calculated. RESULTS: Breast cancer detection doubled from 23 to 46 in 6,425 studies using AWBU with mammography, resulting in an increase in diagnostic yield from 3.6 per 1,000 with mammography alone to 7.2 per 1,000 by adding AWBU. PPV for biopsy based on mammography findings was 39.0% and for AWBU 38.4%. The number of detected invasive cancers 10 mm or less in size tripled from 7 to 21 when AWBU findings were added to mammography. CONCLUSION: AWBU resulted in significant cancer detection improvement compared with mammography alone. Additional detection and the smaller size of invasive cancers may justify this technology's expense for women with dense breasts and/or at high risk for breast cancer.

Large-scale electric energy storage is fundamental to the use of renewable energy. Recently, research and development efforts on room-temperature sodium-ion batteries (NIBs) have been revitalized, as NIBs are considered promising, low-cost alternatives to the current Li-ion battery technology for large-scale applications. Herein, we introduce a novel layered oxide cathode material, Na0.78Ni0.23Mn0.69O2. This new compound provides a high reversible capacity of 138 mAh g–1 and an average potential of 3.25 V vs Na+/Na with a single smooth voltage profile. Its remarkable rate and cycling performances are attributed to the elimination of the P2–O2 phase transition upon cycling to 4.5 V. The first charge process yields an abnormally excess capacity, which has yet to be observed in other P2 layered oxides. Metal K-edge XANES results show that the major charge compensation at the metal site during Na-ion deintercalation is achieved via the oxidation of nickel (Ni2+) ions, whereas, to a large extent, manganese (Mn) ions remain in their Mn4+ state. Interestingly, electron energy loss spectroscopy (EELS) and soft X-ray absorption spectroscopy (sXAS) results reveal differences in electronic structures in the bulk and at the surface of electrochemically cycled particles. At the surface, transition metal ions (TM ions) are in a lower valence state than in the bulk, and the O K-edge prepeak disappears. On the basis of previous reports on related Li-excess LIB cathodes, it is proposed that part of the charge compensation mechanism during the first cycle takes place at the lattice oxygen site, resulting in a surface to bulk transition metal gradient. We believe that by optimizing and controlling oxygen activity, Na layered oxide materials with higher capacities can be designed.

Journal Article Regional Morphology and Pathology of The Prostate Get access John E. McNeal, M.D. John E. McNeal, M.D. Department of Pathology, Herrick Memorial. Hospital, Berkeley, California 94704 Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 49, Issue 3, 1 March 1968, Pages 347–357, https://doi.org/10.1093/ajcp/49.3.347 Published: 01 March 1968 Article history Received: 14 March 1967 Published: 01 March 1968

Author(s): Saver, Jeffrey L; Starkman, Sidney; Eckstein, Marc; Stratton, Samuel J; Pratt, Franklin D; Hamilton, Scott; Conwit, Robin; Liebeskind, David S; Sung, Gene; Kramer, Ian; Moreau, Gary; Goldweber, Robert; Sanossian, Nerses

Abstract Peripheral lymphocytes from 25 patients with chronic lymphocytic leukemia (CLL) and three with chronic lymphosarcoma-cell leukemia, and lymph-node cells from three of four with lymphocytic lymphoma bore on their cell surface IgM, which was readily demonstrated with fluorescein-conjugated antiserums. The lymphosarcoma cell differed from the cell of CLL in possessing much more surface immunoglobulin. Light-chain analysis of the surface IgM showed that cells bore either kappa or lambda determinants, but not both, indicating the clonal nature of these neoplasms. The serum of four leukemic patients was also found to contain small amounts of IgM M-components. Since the B lymphocyte (bone-marrow-derived) of laboratory animals bears large amounts of surface immunoglobulin and the T lymphocyte (thymus processed) does not, the findings favor the B-cell origin of these leukemic cells. A less likely possibility is that the CLL lymphocyte is a derepressed T cell.

Twenty cases of an unusual tumor of the lung are described. This tumor usually presents with multiple small, slowly growing pulmonary nodules. Many cases are detected incidentally. Eighty percent are women, and 50% are less than 40 years of age. Survival with tumor can be quite long. However, one half the patients have died, usually of progressive pulmonary insufficiency. This is a peculiar sclerosing tumor of endothelial cell origin.

A method for the analysis of nucleic acids in microgram amounts of tissue has been devised. Results obtained by this method in rat liver, kidney, and spleen have been compared with results obtained on the same tissues by other methods of analysis for tissue nucleic acid. This method is not designed to replace the more conventional methods of analysis when milligram quantities of tissue are available, although it has been used successfully for that purpose.

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the treatment of anemia and iron deficiency in adult patients with heart disease. METHODS: This guideline is based on published literature in the English language on anemia and iron deficiency from 1947 to July 2012 that was identified using MEDLINE and the Cochrane Library. Literature was reassessed in April 2013, and additional studies were included. Outcomes evaluated for this guideline included mortality; hospitalization; exercise tolerance; quality of life; and cardiovascular events (defined as myocardial infarction, congestive heart failure exacerbation, arrhythmia, or cardiac death) and harms, including hypertension, venous thromboembolic events, and ischemic cerebrovascular events. The target audience for this guideline includes all clinicians, and the target patient population is anemic or iron-deficient adult patients with heart disease. This guideline grades the evidence and recommendations using the ACP's clinical practice guidelines grading system. RECOMMENDATION 1: ACP recommends using a restrictive red blood cell transfusion strategy (trigger hemoglobin threshold of 7 to 8 g/dL compared with higher hemoglobin levels) in hospitalized patients with coronary heart disease. (Grade: weak recommendation; low-quality evidence) RECOMMENDATION 2: ACP recommends against the use of erythropoiesis-stimulating agents in patients with mild to moderate anemia and congestive heart failure or coronary heart disease. (Grade: strong recommendation; moderate-quality evidence).

IMPORTANCE: Children born prematurely who develop retinopathy of prematurity (ROP) often develop myopia, and those who require laser treatment may develop very high myopia, which has considerable clinical consequences. OBJECTIVE: To report refractive outcomes in preterm infants who developed ROP in zone I or zone II posterior as stage 3+ ROP or aggressive posterior ROP (APROP). DESIGN, SETTING, AND PARTICIPANTS: All infants received intravitreal bevacizumab or laser therapy in a prospective, stratified, randomized, controlled, masked, multicenter clinical trial, Bevacizumab Eliminates the Angiogenic Threat for ROP (BEAT-ROP). Children who received intravitreal bevacizumab or laser in the BEAT-ROP clinical trial, with treatment randomized by infant, underwent cycloplegic retinoscopic refraction at a mean age of 2½ years. Fifteen centers with both pediatric and vitreoretinal ophthalmologists participating in level 3 neonatal intensive care units in academic centers with institutional review board approval were included in the trial. Of the originally enrolled 150 infants (300 eyes) in the BEAT-ROP clinical trial, 13 infants (26 eyes) died (6 received intravitreal bevacizumab; 7 received laser) and 19 eyes had intraocular surgery (6 infants bilaterally). Thus, 45 eyes (19 infants bilaterally) were excluded, leaving 131 infants (255 eyes, including 21 eyes that received a successful second treatment for recurrence). INTERVENTIONS: Follow-up of the BEAT-ROP cohort. MAIN OUTCOMES AND MEASURES: Spherical equivalent refractive outcomes and their distribution by ROP zone and treatment. RESULTS: Refractions were available for 109 of 131 eligible infants (83.2%) and 211 of 255 eyes (82.7%). Mean (SD) spherical equivalent refractions were as follows: zone I, -1.51 (3.42) diopters (D) in 52 eyes that received intravitreal bevacizumab and -8.44 (7.57) D in 35 eyes that received laser treatment (P < .001); and zone II posterior, -0.58 (2.53) D in 58 eyes that received intravitreal bevacizumab and -5.83 (5.87) D in 66 eyes that received laser treatment (P < .001). Very high myopia (≥-8.00 D) occurred in zone I in 2 of 52 (3.8%) eyes that received intravitreal bevacizumab and in 18 of 35 (51.4%) eyes that received laser treatment (P < .001). Very high myopia occurred in zone II posterior in 1 of 58 (1.7%) eyes that received intravitreal bevacizumab and in 24 of 66 (36.4%) eyes that received laser treatment (P < .001). CONCLUSIONS AND RELEVANCE: More very high myopia was found in eyes that received laser treatment than in eyes that received intravitreal bevacizumab. This difference is possibly related to anterior segment development that is present with intravitreal bevacizumab but minimal or absent following laser treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00622726.

The quasiharmonic Debye approximation has been implemented within the aflow and Materials Project frameworks for high-throughput computational materials science (Automatic Gibbs Library, agl), in order to calculate thermal properties such as the Debye temperature and the thermal conductivity of materials. We demonstrate that the agl method, which is significantly cheaper computationally compared to the fully ab initio approach, can reliably predict the ordinal ranking of the thermal conductivity for several different classes of semiconductor materials. In particular, a high Pearson (i.e., linear) correlation is obtained between the experimental and agl computed values of the lattice thermal conductivity for a set of 75 compounds including materials with cubic, hexagonal, rhombohedral, and tetragonal symmetry.

The likelihood of a sustained response to a course of interferon in patients with chronic hepatitis C correlates with several clinical and viral factors, including age, viral genotype and initial levels of hepatitis C virus (HCV) RNA in serum. The role of race and ethnicity has not been assessed. We evaluated the association of race with response to interferon in a large randomized, controlled trial using either consensus interferon (9 microg) or interferon alfa-2b (3 million units) given three times weekly for 24 weeks. African-American patients participating in the study were similar to white patients in mean age (43 vs. 42 years) and baseline levels of HCV RNA (3.6 vs. 3.0 million copies/mL) but had lower rates of cirrhosis (5% vs. 12%) and more frequently had viral genotype 1 (88% vs. 66%: P =.004). Most strikingly, the rates of end-of-treatment and sustained virological responses were lower among the 40 African-American patients (5% and 2%) than among the 380 white patients (33% and 12%) (P =.04 and.07). Rates of response among Hispanic and Asian-American patients were not statistically different than non-Hispanic white patients. Median viral levels decreased by week 24 of therapy by 2.5 logs in white patients (from 3.0 to 0.012 million copies/mL) but by only 0.5 logs among African- American patients (from 3.6 to 1.8 million copies/mL). Thus, there are marked racial differences in virological responses to interferon in hepatitis C that must be considered in assessing trials of interferon therapy and in counseling patients regarding treatment. The differences in response rates are as yet unexplained.

Carotid-to-jugular cross circulation between partially hepatectomized and normal rats, via polyethylene cannulas, stimulated incorporation of (14)C-thymidine into hepatic DNA in the normal partners when it was maintained for 19 hours at a flow rate of about 2 milliliters per minute. Cross circulation for 7 hours or less was ineffective.

It is well known that hepatitis C virus (HCV) infection may progress to cirrhosis and is linked to the development of hepatocellular carcinoma (HCC). Previous studies have shown that compensated HCV-cirrhosis is related to a certain morbidity and mortality in European patients, but little is known in regard to the clinical outcomes of a similar group of patients in the United States. This study investigated this category of patients in terms of the incidence of decompensation, development of HCC, mortality, and the predictive risk factors for morbidity and mortality. The potential effects of interferon (IFN) therapy on outcomes of the disease also were assessed. A total of 112 patients with compensated HCV-cirrhosis and a documented history of either intravenous drug abuse (IVDA) or transfusion were consecutively enrolled. The mean follow-up interval was 4.5 (2-7.7) years. The cumulative probabilities for decompensation and development of HCC were 22.2% and 10.1% in 5 years, with an estimated yearly incidence of 4.4% and 2.0%, respectively. The cumulative survival probability was 82.8% from entry and 51.1% from decompensation in 5 years, with estimated yearly events of mortality and liver transplantation of 3.4% and 9. 8%, respectively. It was found that age at entry and initial exposure, initial levels of albumin, platelet count, and prothrombin time (PT) were predictive risk factors for developing decompensation, whereas age at entry and initial exposure, history of transfusion, lower initial levels of albumin, platelet count, and viral load were predictive risk factors for events of mortality and liver transplantation. The incidence of decompensation was significantly lower in patients treated with IFN, but age may have played a contributory role. In contrast, neither HCC development nor mortality was significantly altered by IFN therapy. In conclusion, our study indicated that patients with compensated HCV-cirrhosis in the United States progressed slowly and experienced eventual morbidity and mortality. Once decompensation develops, the disease will be more progressive and result in even higher mortality. Further studies will be required to determine the efficacy of IFN on clinical outcomes in this group of patients.

An accurate assay of diadenosine 5',5'''- P1,P4-tetraphosphate [A(5') pppp(5')A], which was shown to be formed in vitro in the backreaction of the amino acid activation step, has been developed in various cell lines in culture and in normal mouse liver or hepatoma in vivo. Use of radioactive labeling of acid-soluble nucleotides to high specific activity followed by chromatographic separation techniques yielded levels of Ap4A varying from 5 to 0.05 muM (from 30 pmol/mg of protein to 0.15 pmol), depending on the doubling time of the cell line or the proliferative state of the cells. The levels of Ap4A incells is inversely related to their doubling time, varying from 0.1 X 10(-4) of the cellular ATP levels in slowly growing cells to 20 X 10(-4) of the ATP levels of cells with rapid doubling times. The steady-state levels of ATP of different cell lines, although showing some fluctuations, are not related to the doubling time of the cells. Arrest of cellular proliferation by serum deprivation or amino acid starvation, which does not alter the cellular ATP levels more than 2-fold, does nevertheless cause a decrease of 30 to 50-fold in the Ap4A levels. Inhibition of protein synthesis by pactamycin or puromycin, or inhibition of DNA synthesis by hydroxyurea, leads to a more dramatic decrease of 50 to 100-fold in intracellular Ap4A levels. The metabolic lability of Ap4A is also demonstrated by its rapid depletion after decreases in the ATP/ADP ratio. The possibility of Ap4A being a metabolic "signal nucleotide" that is formed at the onset of protein synthesis and is active in positive growth regulation (positive pleiotypic activation) is discussed.

Dielectrics are an important class of materials that are ubiquitous in modern electronic applications. Even though their properties are important for the performance of devices, the number of compounds with known dielectric constant is on the order of a few hundred. Here, we use Density Functional Perturbation Theory as a way to screen for the dielectric constant and refractive index of materials in a fast and computationally efficient way. Our results constitute the largest dielectric tensors database to date, containing 1,056 compounds. Details regarding the computational methodology and technical validation are presented along with the format of our publicly available data. In addition, we integrate our dataset with the Materials Project allowing users easy access to material properties. Finally, we explain how our dataset and calculation methodology can be used in the search for novel dielectric compounds.