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1.
Int J Eat Disord ; 49(3): 260-75, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26711005

ABSTRACT

OBJECTIVE: This article summarizes the literature on obstetric and gynecologic complications associated with eating disorders. METHOD: We performed a comprehensive search of the current literature on obstetric and gynecologic complications associated with eating disorders using PubMed. More recent randomized-controlled trials and larger data sets received priority. We also chose those that we felt would be the most relevant to providers. RESULTS: Common obstetric and gynecologic complications for women with eating disorders include infertility, unplanned pregnancy, miscarriage, poor nutrition during pregnancy, having a baby with small head circumference, postpartum depression and anxiety, sexual dysfunction and complications in the treatment for gynecologic cancers. There are also unique associations by eating disorder diagnosis, such as earlier cessation of breastfeeding in anorexia nervosa; increased polycystic ovarian syndrome in bulimia nervosa; and complications of obesity as a result of binge eating disorder. DISCUSSION: We focus on possible biological and psychosocial factors underpinning risk for poor obstetric and gynecological outcomes in eating disorders. Understanding these factors may improve both our understanding of the reproductive needs of women with eating disorders and their medical outcomes. We also highlight the importance of building multidisciplinary teams to provide comprehensive care to women with eating disorders during the reproductive years.


Subject(s)
Anorexia Nervosa/complications , Bulimia Nervosa/complications , Pregnancy Complications/diagnosis , Female , Humans , Pregnancy
2.
Rev Sci Instrum ; 94(5)2023 May 01.
Article in English | MEDLINE | ID: mdl-37184347

ABSTRACT

We report on progress implementing and testing cryogenically cooled platforms for Magnetized Liner Inertial Fusion (MagLIF) experiments. Two cryogenically cooled experimental platforms were developed: an integrated platform fielded on the Z pulsed power generator that combines magnetization, laser preheat, and pulsed-power-driven fuel compression and a laser-only platform in a separate chamber that enables measurements of the laser preheat energy using shadowgraphy measurements. The laser-only experiments suggest that ∼89% ± 10% of the incident energy is coupled to the fuel in cooled targets across the energy range tested, significantly higher than previous warm experiments that achieved at most 67% coupling and in line with simulation predictions. The laser preheat configuration was applied to a cryogenically cooled integrated experiment that used a novel cryostat configuration that cooled the MagLIF liner from both ends. The integrated experiment, z3576, coupled 2.32 ± 0.25 kJ preheat energy to the fuel, the highest to-date, demonstrated excellent temperature control and nominal current delivery, and produced one of the highest pressure stagnations as determined by a Bayesian analysis of the data.

3.
Minerva Urol Nefrol ; 64(2): 149-52, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22617309

ABSTRACT

We present a the case of 58-year old man who was admitted to hospital with typical clinical features (bloody nasal discharge, arthralgia, acute kidney injury with a nephritic syndrome) consisting with Wegeners granulomatosis (WG). CT-scan showed pulmonary nodules and antineutrophil cytoplasmatic antibodies (ANCA) were elevated. A kidney biopsy showed a crescentic glomerulonephritis, but not pauci-immune-immune with a histopathological staining of a mesangioproliferative IgA-glomerulonephritis. The patient was put on prednisolone and i.v. cyclophosphamid (CYCLOPS-protocol (1). The anti-proteinase-3 antibody titer decreased and the CT-scan showed decreased activity of Wegener's granulomatosis (BVAS 26 dropped to 2) and the patient`s serum creatinine level was stable. The exact nosological relation of mesangial IgA-nephropathy to WG is still unclear. This case underlines that knowledge of renal histology is essential in the management of patients with renal disease, especially in patients with hematuria and/or proeinuria with positive ANCA.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic/blood , Glomerulonephritis, IGA/diagnosis , Glomerulonephritis, IGA/immunology , Granulomatosis with Polyangiitis/diagnosis , Granulomatosis with Polyangiitis/immunology , Immunoglobulin A/blood , Immunologic Factors/blood , Biomarkers/blood , Cyclophosphamide/therapeutic use , Drug Therapy, Combination , Follow-Up Studies , Glomerulonephritis, IGA/blood , Glomerulonephritis, IGA/drug therapy , Glucocorticoids/therapeutic use , Granulomatosis with Polyangiitis/blood , Granulomatosis with Polyangiitis/drug therapy , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Prednisolone/therapeutic use , Tomography, X-Ray Computed , Treatment Outcome
4.
Internist (Berl) ; 52(10): 1238-42, 2011 Oct.
Article in German | MEDLINE | ID: mdl-21161146

ABSTRACT

Hypokalemia is a common finding. The clinical presentation can be paralyses and cardiac arrhythmias. We present a normotensive young woman with salt appetite, cramps and palpitations. In our case report the patient shows a positive family history for hypopotassemia, a metabolic alkalosis with hypotension, and hypocalciuria with an increased urinary potassium loss. The levels of renin and aldosterone were elevated. After a negative testing for metabolites of diuretics, we obtained a positive result of the suspected SLC12A3 genetic test. This mutation leads to a failure of the thiazide-sensitive sodium-2-chloride-cotransporter, the so called Gitelman syndrome, which presents similar to a chronic thiazide therapy. The Gitelman syndrome is a rare disease with renal potassium loss and hypotension. Especially in young patients around the age of twenty or in patients with chronic intractable hypopotassemia a Gitelman syndrome should be considered.


Subject(s)
Arrhythmias, Cardiac/etiology , Gitelman Syndrome/diagnosis , Gitelman Syndrome/genetics , Hypokalemia/diagnosis , Hypokalemia/genetics , Muscle Cramp/etiology , Receptors, Drug/genetics , Sodium Chloride, Dietary/administration & dosage , Symporters/genetics , Diagnosis, Differential , Diseases in Twins/diagnosis , Diseases in Twins/genetics , Female , Humans , Solute Carrier Family 12, Member 3 , Twins, Monozygotic , Young Adult
5.
Methods Find Exp Clin Pharmacol ; 32(2): 129-32, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20401350

ABSTRACT

GanedenBC(30), a probiotic, has been shown to significantly increase T-cell production of TNF-alpha after ex vivo exposure to a strain of adenovirus (AdenoVI) or influenza A (H3N2 Texas strain [FluTex]). The current controlled study was designed to further evaluate the effect of GanedenBC(30) on immunological marker levels following viral exposure. Ten healthy subjects' baseline immunological marker levels were analyzed. Subjects consumed 1 capsule/day of GanedenBC(30) for 28 days and returned for post-treatment immunological marker evaluation. Subjects' baseline measurements served as their own control. All subjects completed the study with no adverse events; however, one subject was excluded from the final analysis based on a reasonable consideration as an outlier. CD3+CD69+ cells, IL-6, IL-8, interferon-gamma (IFN-gamma) and TNF-alpha levels were increased after exposure to AdenoVI and FluTex. IL-1beta levels also increased after exposure to AdenoVI but were decreased after ex vivo exposure to FluTex. CD3+CD69+ cells increased significantly (P = 0.023) after exposure to both viral strains. Differences in IL-8 levels after FluTex exposure achieved statistical significance (P = 0.039) as did IFN-gamma levels after AdenoVI exposure (P = 0.039). A regimen of one capsule per day containing 500 million CFU of GanedenBC30 may be a safe and effective option for enhancing the immunological response to common viral respiratory tract infections.


Subject(s)
Adenovirus Infections, Human/immunology , Influenza, Human/immunology , Probiotics/pharmacology , Adenoviridae/immunology , Adolescent , Adult , Biomarkers/metabolism , Female , Humans , Influenza A Virus, H3N2 Subtype/immunology , Interferon-gamma/immunology , Interleukin-8/immunology , Male , Probiotics/adverse effects , Respiratory Tract Infections/immunology , Respiratory Tract Infections/virology , Young Adult
6.
Med Klin Intensivmed Notfmed ; 115(4): 275-280, 2020 May.
Article in German | MEDLINE | ID: mdl-30725274

ABSTRACT

Acid-base disorders and in particular metabolic acidosis are very common in critically ill patients and contribute significantly to morbidity and mortality. We shed light on the most common causes, the pathophysiology and treatments. Particular attention will be paid to the common practice of substituting sodium bicarbonate in the light of recent study results.


Subject(s)
Acidosis/diagnosis , Acidosis/therapy , Bicarbonates , Acid-Base Equilibrium , Critical Illness , Humans
7.
Science ; 183(4128): 959-62, 1974 Mar 08.
Article in English | MEDLINE | ID: mdl-17756756

ABSTRACT

Extensive dating of the fossil corals associated with the Waimanalo shoreline on Oahu has shown that 120,000 years ago the ocean was approximately 7.6 meters above its present level. Corals grown during that time constitute a major portion of the subaerial reef-derived material on the island, with exposures ranging from about 10 meters to near sea level. This evidence corroborates the notion that 120,000 years before the present was the last time during which the sea stood significantly higher than it does today. The reported benches at 3.7, 1.5, and 0.6 meters, if not of Recent origin, could be features created by brief halts of the sea during rapid regression shortly after the Waimanalo high stand.

8.
Nephron Clin Pract ; 113(2): c88-95, 2009.
Article in English | MEDLINE | ID: mdl-19602904

ABSTRACT

BACKGROUND: Increased local levels of fibrogenic growth hormones contribute substantially to the process of encapsulating peritoneal sclerosis (EPS) in animal models. METHODS: We analyzed probes from patients with normal kidney function (n = 10), with normal kidney function and inflammation (n = 10), on PD without (n = 10) and with EPS (n = 9). We investigated the degree of fibrosis and the number of vessels and vasculopathy. Additionally, we investigated the expression of NFkappaB, TGFbeta1, TGFbeta1 receptor, TGFbeta2, TGFbeta2 receptor, FGF-BP, CTGF and VEGF by immunohistochemistry. RESULTS: In EPS, we found an exclusive upregulation of VEGF (normal 0, appendicitis 1.0 +/- 1.2, PD 1.7 +/- 1.8 and EPS 5.7 +/- 4.4; p < 0.0001), whereas in PD, CTGF was significantly increased (normal 6.0 +/- 2.8, appendicitis 7.3 +/- 2.5, PD 10.0 +/- 1.8 and EPS 7.3 +/- 2.1; p = 0.0059). The results for the TGFbeta system and NFkappaB were not uniform, in EPS no increases were demonstrable. Vasculopathy was significantly more pronounced in EPS (normal 0.4 +/- 0.5, appendicitis 0.2 +/- 0.3, PD 1.0 +/- 0.7 and EPS 1.6 +/- 1.2; p < 0.0001) than in PD or inflammation (normal 30 +/- 16, appendicitis 82 +/- 48, PD 1,936 +/- 952 and EPS 2,613 +/- 1,209; p < 0.0001), whereas the density of vessels were decreased (normal 125 +/- 114, appendicitis 817 +/- 347, PD 81 +/- 57 and EPS 36 +/- 33; p < 0.0001). CONCLUSIONS: The process of EPS was associated with increased VEGF in the peritoneum. The reduced density of vessels compared with marked fibrosis could point to hypoxia as an inducer.


Subject(s)
Appendicitis/complications , Appendicitis/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Peritoneal Fibrosis/complications , Peritoneal Fibrosis/metabolism , Adult , Aged , Female , Humans , Male
9.
Clin Nephrol ; 69(2): 127-9, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18218306

ABSTRACT

Like any other implanted foreign body, the different parts of pacemakers (pulse generator pocket, epicardial or transvenous leads) can become infected. Staphylococcus aureus and coagulase-negative staphylococci are the causative organisms in most of the cases (65 â 75%), propionibacterium is described to be involved in only 1% of cases. This report describes a case of nephritic sediment in a young female patient with a pacemaker implantation 9 years ago because of a third degree atrioventricular block, in which a battery exchange was necessary 2.5 years ago. This young patient was referred from a nephrologist for renal biopsy because of a nephritic sediment and diffuse complaints including low-grade fever with a suspected underlying autoimmune disease. The laboratory examinations were all negative with the exception of a diminished C3 complement level. Blood cultures were positive for propionibacterium, but the microbiologists were considering it as a contamination. 11 more blood cultures collected thereafter were all positive and a transesophageal ultrasound revealed a small vegetation at 1 of the transvenous electrodes of the pacemaker. Because of a penicillin allergy she was treated with clindamycin, and the blood cultures were negative after a few days. After a full course (7 weeks) of antibiotic treatment the C3 complement level normalized and a series of 10 blood cultures remained negative 10 â 15 days after discontinuation of antibiotic therapy. Discussing all the differential diagnoses of a nephritic sediment combined with hypocomplementemia, positive blood cultures and a vegetation on a pacemaker electrode in the transesophageal ultrasound, the diagnosis of an immune complex glomerulonephritis due to a propionibacterium pacemaker infection needs no confirmation by renal biopsy.


Subject(s)
Gram-Positive Bacterial Infections/microbiology , Nephritis/complications , Pacemaker, Artificial/adverse effects , Propionibacterium/isolation & purification , Prosthesis-Related Infections/microbiology , Adult , Anti-Bacterial Agents/therapeutic use , Atrioventricular Block/therapy , Female , Follow-Up Studies , Gram-Positive Bacterial Infections/complications , Gram-Positive Bacterial Infections/drug therapy , Humans , Nephritis/drug therapy , Prosthesis-Related Infections/complications , Prosthesis-Related Infections/drug therapy
10.
Math Biosci Eng ; 16(1): 265-291, 2018 12 13.
Article in English | MEDLINE | ID: mdl-30674120

ABSTRACT

We propose to endow evolutionary gamemodels with changes of the phenotypes adjustment during the transient generations performed by the parameters in the payoff matrix which determine the fitness resulting from different interactions between players. These changes represent an alteration of access to external resources which, in turn, may reflect anticancer treatment. In the case of spatial games, these functions are represented by an additional lattice where another and parallel game based on cellular automata is performed. The main assumption of the spatial games is that each cell on the lattice is represented by a player following only one strategy. We propose to consider cells on the spatial lattice as heterogeneous (instead of homogeneous), so that each particular player may contain mixed phenotypes. Spatial games of the type, proposed by us, are called multidimensional spatial evolutionary games (MSEG). It may happen that within the population, all of the players have diverse phenotypes (which probably better describes biological phenomena). The additional lattice representing the evolution of resources increases only the dimension of the lattice in the MSEG.


Subject(s)
Game Theory , Neoplasms/physiopathology , Biological Evolution , Humans , Intercellular Signaling Peptides and Proteins , Models, Genetic , Neoplasms/genetics , Neovascularization, Pathologic , Phenotype
11.
Drugs Today (Barc) ; 54(9): 561-575, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30303496

ABSTRACT

Cancer patients often exhibit preexisting renal impairment and are simultaneously at risk for developing further kidney injury due to direct or indirect complications of oncological therapies. The nature of kidney injury is highly dependent on the therapy regimen used, and the spectrum of possible kidney stressors has widened as a result of the development of new therapeutic modalities such as molecular therapy or immunotherapy. Indirect renal complications are often due to volume depletion or other therapy-related side effects. Direct toxicity from "classic" chemotherapy treatments such as cisplatin usually leads to acute tubular necrosis, whereas treatment with protein kinase inhibitors is more likely to cause disorders such as thrombotic microangiopathy. Immunotherapy often affects kidneys through the development of acute interstitial nephritis. Because of the high risk of nephrological complications in oncological patients, close monitoring of renal function and the early involvement of a nephrologist are strongly recommended.


Subject(s)
Antineoplastic Agents/adverse effects , Immunotherapy/adverse effects , Kidney Diseases/chemically induced , Protein Kinase Inhibitors/adverse effects , Humans , Molecular Targeted Therapy/adverse effects
12.
Rev Sci Instrum ; 89(10): 10F102, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30399823

ABSTRACT

X-ray diffraction measurements to characterize phase transitions of dynamically compressed high-Z matter at Mbar pressures require both sufficient photon energy and fluence to create data with high fidelity in a single shot. Large-scale laser systems can be used to generate x-ray sources above 10 keV utilizing line radiation of mid-Z elements. However, the laser-to-x-ray energy conversion efficiency at these energies is low, and thermal x-rays or hot electrons result in unwanted background. We employ polycapillary x-ray lenses in powder x-ray diffraction measurements using solid target x-ray emission from either the Z-Beamlet long-pulse or the Z-Petawatt (ZPW) short-pulse laser systems at Sandia National Laboratories. Polycapillary lenses allow for a 100-fold fluence increase compared to a conventional pinhole aperture while simultaneously reducing the background significantly. This enables diffraction measurements up to 16 keV at the few-photon signal level as well as diffraction experiments with ZPW at full intensity.

13.
Nat Commun ; 9(1): 280, 2018 01 18.
Article in English | MEDLINE | ID: mdl-29348402

ABSTRACT

High-intensity lasers interacting with solid foils produce copious numbers of relativistic electrons, which in turn create strong sheath electric fields around the target. The proton beams accelerated in such fields have remarkable properties, enabling ultrafast radiography of plasma phenomena or isochoric heating of dense materials. In view of longer-term multidisciplinary purposes (e.g., spallation neutron sources or cancer therapy), the current challenge is to achieve proton energies well in excess of 100 MeV, which is commonly thought to be possible by raising the on-target laser intensity. Here we present experimental and numerical results demonstrating that magnetostatic fields self-generated on the target surface may pose a fundamental limit to sheath-driven ion acceleration for high enough laser intensities. Those fields can be strong enough (~105 T at laser intensities ~1021 W cm-2) to magnetize the sheath electrons and deflect protons off the accelerating region, hence degrading the maximum energy the latter can acquire.

14.
J Clin Invest ; 77(2): 396-404, 1986 Feb.
Article in English | MEDLINE | ID: mdl-2418062

ABSTRACT

Stratification of human epidermal cells into multilayered sheets composed of basal and suprabasal layers (resembling the stratum germinativum and stratum spinosum of the epidermis) was studied in a dermal component-free culture system. Although no stratum corneum developed in vitro, this culture system provided a method to study early events in human keratinocyte differentiation. Multiparameter flow cytometric analysis of acridine orange-stained epidermal cells from these cultures revealed three distinct subpopulations differing in cell size, RNA content, and cell cycle kinetics. The first subpopulation was composed of small basal keratinocytes with low RNA content and a long generation time. The second subpopulation consisted of larger keratinocytes, having higher RNA content and a significantly shorter generation time. Finally, the third subpopulation contained the largest cells, which did not divide, and represent the more terminally differentiated keratinocytes. This in vitro approach provides discriminating cytochemical parameters by which the maturity of the epidermal cell sheets can be assessed prior to grafting onto human burn patients.


Subject(s)
Epidermal Cells , Keratins/metabolism , Burns/therapy , Cell Adhesion , Cell Cycle , Cell Differentiation , Cell Division , Cells, Cultured , DNA/metabolism , Epidermis/metabolism , Epithelium/transplantation , Humans , Kinetics , RNA/metabolism
16.
Drugs Today (Barc) ; 53(6): 349-356, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28799580

ABSTRACT

Acute kidney injury (AKI) is a common syndrome with increased mortality, a heavy burden of illness and high cost. The Kidney Disease Improving Global Outcomes (KDIGO) criteria for staging of AKI have been validated in large patient cohorts and classify AKI into three stages. In order to achieve prevention or early therapy, the focus of scientific interest is early detection and risk prediction of AKI. The combination of the two cell cycle arrest markers [TIMP-2]·[IGFBP7] in the urine shows good results in the risk prediction of AKI in different clinical settings (intensive care medicine, sepsis, cardiac surgery, emergency department). Clinical use is currently being tested in different randomized intervention studies.


Subject(s)
Acute Kidney Injury/urine , Insulin-Like Growth Factor Binding Proteins/urine , Tissue Inhibitor of Metalloproteinase-2/urine , Acute Kidney Injury/blood , Biomarkers , Cardiac Surgical Procedures , Clinical Trials as Topic , Creatinine/blood , Emergencies , Humans , Postoperative Complications/urine , Predictive Value of Tests , Risk Assessment , Sepsis/urine , Urinalysis/methods
17.
J Natl Cancer Inst ; 80(5): 337-44, 1988 May 04.
Article in English | MEDLINE | ID: mdl-2833601

ABSTRACT

A mathematical model of the progression kinetics of lung cancer was described and used to shed light on the natural history of adenocarcinoma and large cell carcinoma of lung from data collected in screening studies of male smokers by the Memorial Sloan-Kettering Cancer Center and The Johns Hopkins Medical Institutions. In both programs, estimates of the mean duration of early-stage adenocarcinoma or large cell carcinoma of lung ranged upward from 4 years, and estimates of the probability of detecting it in early-stage disease ranged downward from .16. The probabilities of curing early-stage disease through surgical treatment were found to be at most .52 and .13 in the New York and Baltimore studies, respectively. These estimates led to the conclusion that expected reduction in mortality from adenocarcinoma and large cell carcinoma of lung as due to annual x-ray screening from age 45 to 80 years is not greater than 18% in New York and 5% in Baltimore.


Subject(s)
Adenocarcinoma/mortality , Carcinoma, Small Cell/mortality , Lung Neoplasms/mortality , Adenocarcinoma/diagnosis , Adenocarcinoma/therapy , Carcinoma, Small Cell/diagnosis , Carcinoma, Small Cell/therapy , Clinical Trials as Topic , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/therapy , Male , Models, Biological , Probability , Radiography, Thoracic , Time Factors
18.
J Natl Cancer Inst ; 83(10): 701-7, 1991 May 15.
Article in English | MEDLINE | ID: mdl-2023271

ABSTRACT

In our prospective study, flow cytometric analysis of cellular DNA and RNA content was performed on unfixed fresh specimens of colorectal adenocarcinoma taken from 176 patients. Of the 176 tumors, 113 (64%) were aneuploid. There was no correlation between aneuploidy and tumor stage, grade, location, or size. After a median follow-up of 5.6 years, no correlation between DNA or RNA content and patient survival was found. DNA content alone was not an independent prognostic factor when the colorectal carcinomas were segregated by curable and incurable stages. However, normal mucosa, diploid tumors, and aneuploid tumors showed progressively higher proliferation and higher RNA and DNA indices. Proliferative fraction--defined as the percentage of cells in S + G2 and M phases of the cell cycle--was significantly related to ploidy and to Dukes' stage. Despite these correlations, we did not detect a significant influence of proliferative fraction on survival when patients were segregated above or below the mean proliferative fraction for all tumors. More accurate methods of identifying the proliferative fraction of tumor cells are currently being pursued. While the role of flow cytometry in the evaluation and management of patients with colorectal carcinoma is still undefined for a number of other cellular parameters, it seems unlikely that DNA index, RNA index, or the proliferative fractions calculated from the DNA histogram, will, of themselves, represent independent prognostic factors.


Subject(s)
Adenocarcinoma/metabolism , Colorectal Neoplasms/metabolism , DNA, Neoplasm/metabolism , RNA, Neoplasm/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Aneuploidy , Cell Division , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , DNA, Neoplasm/genetics , Diploidy , Female , Flow Cytometry , Humans , Male , Middle Aged , Mitosis , Prognosis , Prospective Studies , RNA, Neoplasm/genetics , S Phase , Survival Analysis
19.
Cancer Res ; 49(22): 6347-51, 1989 Nov 15.
Article in English | MEDLINE | ID: mdl-2804980

ABSTRACT

DNA content and in situ sensitivity to denaturation were analyzed by flow cytometry of individual cell nuclei isolated from 40 breast carcinomas, nine fibroadenomas, and 14 samples of normal breast tissue. The extent of DNA denaturation induced by acid was expressed as alpha t, which represents the fraction of DNA staining metachromatically red with the fluorochrome acridine orange. In all cases of normal breast tissue DNA was very sensitive to denaturation and the frequency distribution of alpha t values was unimodal with over 90% of cells having alpha t above 0.6. All fibroadenomas were diploid; four had unimodal alpha t as in normal tissue and five had a bimodal distribution with an additional peak below 0.6. Twenty-seven adenocarcinomas (67%) had a DNA index above 1.0; of these 24 had bimodal alpha t distributions. Among 13 diploid carcinomas 10 had bimodal alpha t distributions. Statistically significant differences were observed in alpha t distributions of normal versus tumor breast tissue (P less than 0.005). In normal tissue and in all tumors a predominant proportion of cells with S and G2 + M DNA content were characterized by DNA resistant to denaturation (alpha t below 0.6). Of interest, the diploid cells from aneuploid tumors which may represent reactive host cells often displayed bimodal distributions of alpha t. These results may be interpreted in light of earlier studies demonstrating increased resistance of DNA to denaturation in diffuse chromatin of proliferating and/or transcriptionally active cells, and greater sensitivity to denaturation of DNA in condensed chromatin of quiescent cells. Thus, the presence of the second peaks representing cells with low alpha t values in breast tumors may indicate a high proportion of proliferating cells, whereas high alpha t populations may represent quiescent and differentiating (condensed chromatin) or dying (pycnotic nuclei) cells. It is likely that the low alpha t diploid cells detected in aneuploid tumors may represent the reactive (transcriptionally active and/or proliferating) infiltrating host cells (i.e., lymphocytes, monocytes) whose presence may also be of prognostic value. The data suggest that a DNA denaturability assay may be useful to characterize tumor and infiltrating host cell populations.


Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/analysis , Cell Nucleus/analysis , DNA, Neoplasm/analysis , DNA/analysis , Nucleic Acid Denaturation , Acridine Orange , Adenofibroma/analysis , Adult , Aged , Animals , Breast/analysis , Carcinoma/analysis , Dogs , Female , Flow Cytometry , Humans , Luminescent Measurements , Middle Aged
20.
Cancer Res ; 50(24): 7912-4, 1990 Dec 15.
Article in English | MEDLINE | ID: mdl-2253231

ABSTRACT

DNA content and sensitivity of DNA in situ to denaturation by acid were analyzed by flow cytometry of cell nuclei freshly isolated from the bladder tumors of 32 patients and were compared with normal urothelium of 8 subjects. DNA sensitivity to denaturation was assessed in RNase treated cells by acridine orange metachromasia following partial denaturation with hydrochloric acid; the extent of denatured DNA is given as an index (alpha t), representing the ratio of single stranded to total DNA per nucleus. Of the low stage tumors (papillomas, Ta, Tis, T1) 11 of 18 (61%) were aneuploid. Of the high stage tumors (T2 and T3a) 11 of 14 (79%) were aneuploid. DNA in nuclei of normal transitional epithelium was very sensitive to denaturation, as was papilloma, characterized by nuclear alpha t indices of 0.73 +/- 0.01 (SD) and 0.73 +/- 0.04, respectively. Nuclear DNA of noninvasive carcinomas (Ta, Tis) was significantly more resistant to denaturation (alpha t = 0.69), and DNA of invasive carcinomas was most resistant, ranging from alpha t = 0.61 (T1 tumors) to alpha t = 0.59 (T2 tumors) to alpha t = 0.57 (T3 tumors). High stage tumors as a group (T2, T3) had significantly different (lower) alpha t values than low stage tumors (Ta, Tis, T1). In model cell culture systems it is known that a decrease in alpha t index, i.e., greater resistance to denaturability, occurs as cells transit from resting phase into the cell cycle. Whether the alpha t index can be used to estimate resting vesus cycling cells of human tumors is still speculative; changes in DNA denaturability also are known to occur with changes in chromatin structure during cell differentiation and in transformation. However, the empirical relationship between alpha t index and tumor stage, of itself, may prove clinically useful in identifying more advanced and perhaps more aggressive tumors.


Subject(s)
DNA, Neoplasm/metabolism , Nucleic Acid Denaturation , Urinary Bladder Neoplasms/pathology , Biopsy , Carcinoma/pathology , DNA/metabolism , Humans , Neoplasm Invasiveness , Neoplasm Staging , Papilloma/pathology , Reference Values , Urinary Bladder Neoplasms/surgery
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