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Fluorescent in situ identification of human marker chromosomes using flow sorting and Alu element-mediated PCR.

A novel approach to the identification of human chromosomes has been developed. Chromosomal in situ hybridization (or "chromosome painting") … ce of this work is that chromosome paints specific for the common aberrant chromosomes, such as the Philadelphia chromosome, can be generated and made widely available. These may find particular use in the analysis of complex or masked chromosomal translocations.

Vaginal and vulvar adenosis. An unsuspected side effect of CO2 laser vaporization.

During a 15-month period, September 1984 through January 1986, 10 women who were treated in the Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, Pennsylvania Hospital, Philadelphia, Pennsylvania, developed vaginal or vulvar adenosis after CO2 laser vaporization. The indications for therapy were condylomata of the cervix, vagina and vulva refractory to conservative management in 3 patients, vulvar intraepithelial neoplasia in 3, lichen sclerosus in 1 and cervical intraepithelial neoplasia with condylomata on the cervix and vagina in 3. All the patients underwent treatme…

Mutations of the ras protooncogenes in chronic myelogenous leukemia: a high frequency of ras mutations in bcr/abl rearrangement-negative chronic myelogenous leukemia.

Seventy cases of chronic myelogenous leukemia (CML) were analyzed for the presence of ras mutations using polymerase chain reaction (PCR), oligonucleotide hybridization, and direct PCR sequencing. All cases had preceding cytogenetic and bcr rearrangement studies. Aberrant ras genes were detected in none of 39 patients with Philadelphia (Ph) chromosome or bcr/abl rearrangement positive chronic-phase CML and in only 1 of 18 patients in blast crisis, suggesting that ras mutations have little or no role in initiation or progression of common CML. Seven of 13, or 54% of patients with bcr/abl rearra…

Preliminary observations on maternal rating of health of children: data from three subspecialty clinics.

Although routinely used in health surveys, the factors affecting maternal perceptions of health in children, especially those with health problems, have received little examination. This question has been addressed using a telephone interview of families of 483 children followed in one of three clinics at Children's Hospital of Philadelphia: the Neonatal Follow-up Program, the Pediatric Rheumatology Center and the Spina Bifida Program. Limitations in activities of daily living due to the health of the child, medical care use and variables indicative of socio-economic disadvantage were associat…

Association of large granular lymphocyte/natural killer cell proliferative disease and second hematologic malignancy.

We describe the first three patients with a large granular lymphocytosis/lymphocytic leukemia and another blood malignancy. In two, a myeloproliferative disorder developed soon after the diagnosis of abnormal proliferation of large granular lymphocytes-natural killer (LGL-NK) cells, a myelodysplastic syndrome evolving to acute leukemia and a Philadelphia-positive chronic myelogenous leukemia. In these cases, LGLs expressed the phenotype of CD3+ NK and CD3- NK cells, respectively, and were clonal in the first patient as demonstrated by T-cell receptor gene rearrangement study. In the third case…

[Diseases of the lungs caused by legionella species (author's transl)].

Ever since the 1976 Philadelphia epidemic and the isolation of the causative organism by MacDade in 1977, numerous clinical, epidemiological and bacteriological papers have stressed the significance of the "new" causative organisms responsible for serious cases of pneumonia. On the basis of knowledge available at present, the Legionellaceae family accounts for these bacteria. There are five different species in the genus Legionella: L. pneumophila, L. micdadei, L. bozemannii, L. dumoffii and L. gormanii. L. pneumophila occurs most frequently and has six serogroups (Serogroups 1-6), the first o…

Proliferation, differentiation, and cytogenetics of chronic leukemic B lymphocytes cultured with mitomycin-treated normal cells.

Lymphocytes from 6 patients with chronic lymphocytic leukemia of the B-cell variety (B-CLL) were cultured with equal numbers of mitomycin-tr … volving the short arm of chromosome 9. One patient had a translocation from 22q to 14q, producing a Philadelphia chromosome as well as the 14q+ marker. The results indicate that the neoplastic lymphocytes of B-CLL may proliferate and differentiate when appropriately stimulated in vitro, and that chromosomally abnormal clones are not uncommon. With several tech …

Transitioning From CKD to Kidney Failure: A Mixed-Methods Study of Patient Perspectives.

RATIONALE & OBJECTIVE: The transition from chronic kidney disease (CKD) to kidney failure (KF) is life-changing. We explored the KF transition and dialysis start experiences of patients with varying degrees of prior nephrology care and preparation. STUDY DESIGN: Convergent parallel mixed-methods study using surveys and interviews. SETTING & PARTICIPANTS: Data were collected from December 2018 to January 2020 among adults in metropolitan Philadelphia who had recently transitioned from CKD to KF and started dialysis. ANALYTICAL APPROACH: Participants were categorized as having had (1) some pr…

Electrocardiogram-based deep learning to predict left ventricular systolic dysfunction in paediatric and adult congenital heart disease in the USA: a multicentre modelling study.

BACKGROUND: Left ventricular systolic dysfunction (LVSD) is independently associated with cardiovascular events in patients with congenital … atient at Boston Children's Hospital (Boston, MA, USA) and externally at the Children's Hospital of Philadelphia (Philadelphia, PA, USA) using area under the receiver operating (AUROC) and precision-recall (AUPRC) curves. FINDINGS: The training cohort comprised 124 265 ECG-echocardiogram pairs (49 158 patients; median age 10·5 years [IQR 3·5-16·8]; 3381 [2·7% …

Acute Pancreatitis Complicating L-asparaginase Therapy in Pediatric Oncology: A Case Report.

Acute pancreatitis is a recognized toxicity of L-asparaginase therapy during the treatment of pediatric acute lymphoblastic leukemia (ALL). Its management requires a delicate balance between avoiding leukemic relapse and preventing pancreatic recurrence. We report the case of a five-year-and-eight-month-old girl with Philadelphia chromosome-positive B-cell ALL, initially treated with imatinib combined with the high-risk MARALL 2006 protocol, and subsequently with the COOPRALL 97 protocol following an isolated central nervous system relapse. Seventy-two hours after the 18th cumulative administr…

Unilateral vision loss as the initial symptom of chronic myeloid leukemia with bilateral retinal infiltration: a case report.

BACKGROUND: Ophthalmic manifestations as the initial presentation of chronic myeloid leukemia (CML) are rare. CASE PRESENTATION: This case … vision in the right eye. Systemic evaluation revealed critical hyperleukocytosis, splenomegaly, and Philadelphia chromosome positivity, confirming CML. The subsequent MRI during remission showed no abnormality. Treatment with hydroxyurea and nilotinib rapidly normalized white blood cell counts and reached major molecular response (MMR) along with complete visu …

The thrombopoietin receptor in myeloproliferative neoplasms: A unifying mechanism of disease pathogenesis and therapeutic targeting.

The Philadelphia chromosome negative myeloproliferative neoplasms (MPNs), essential thrombocythemia, polycythemia vera, and primary myelofibrosis, are clonal hematopoietic stem cell disorders unified by constitutive thrombopoietin receptor (MPL) signaling. All 3 MPN driver mutations, JAK2, CALR, and MPL, converge on enhanced MPL signaling, establishing the thrombopoietin (TPO)/MPL axis as the central molecular hub linking clonal hematopoiesis to the cardinal manifestations of MPN, including thrombosis, hemorrhage, and fibrotic progression. As the principal regulator of hematopoietic stem cell …

Помимо CAR-T: Предотвращение и лечение релапса в гематологических злодеяниях B-Cell.

Цимерическая антигенная лейкемия (КАР) Т-клетотерапия произвела революцию в области лечения рентгеновской/рефракторной (R/R) острой лимфоболической лейкемии (B-LAL), неходгкинской лимфомы (NHL) и множественной миеломы (MM); однако значительная часть пациентов в конечном итоге, несмотря на первоначальные ответные меры, вновь заболела. В настоящем обзоре содержится краткий обзор клеточной терапии CAR-T, включая ее производственный процесс и связанные с этим токсичные свойства, до изучения биологических механизмов, лежащих в основе рецидива после CAR-T в B-ALL, NHL-особенно большой лимфомы B-клет

Совпадение в аннотации оригинала
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape of relapsed/refractory (R/R) B-cell acute lymphobl … transplantation (allo-HSCT), maintenance with targeted agents (e.g., tyrosine kinase inhibitors in Philadelphia chromosome-positive B-ALL), and CAR-T cell reinfusion, whereas relapse management is disease-specific and increasingly incorporates novel therapeutic agents, including bispecific antibodies (BsAbs) and other targeted therapies. However, current evid …

Myeloproliferative neoplasms: young patients, current data and future considerations.

The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders predominantly occurring in elderly, whereas in children and young adults are quite infrequent. Therefore, less is known about clinical presentation, genetic abnormalities, prognosis and best management strategies for this groups of patients. Currently, more cases of younger MPN patients are diagnosed. Nevertheless, diagnosis of MPNs, especially in childhood, may be difficult due to lower incidence of JAK2V617F and CALR mutations and differences in peripheral blood counts between a…

Chronic myeloproliferative neoplasms with concomitant CALR mutation and BCR::ABL1 translocation: diagnostic and therapeutic implications of a rare hybrid disease.

Myeloproliferative neoplasms (MPNs) are subdivided into Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) and Ph-negative MPNs. BCR::ABL1 translocation is essential for the development and diagnosis of CML; on the other hand, the majority of Ph-negative MPNs are characterized by generally mutually exclusive mutations of Janus kinase 2 (JAK2), calreticulin (CALR), or thrombopoietin receptor/myeloproliferative leukemia (MPL). CALR mutations have been described essentially in JAK2 and MPL wild-type essential thrombocythemia and primary myelofibrosis. Rarely coexisting CALR and …

Efficacy and safety outcomes in Japanese patients with low-risk polycythemia vera treated with ropeginterferon alfa-2b.

Polycythemia vera (PV) is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by clonal erythrocytosis. A phase 2 study reported that ropeginterferon alfa-2b is a well-tolerated and effective treatment for PV in Japanese patients. This post hoc analysis of the phase 2 data further evaluated outcomes in patients at low risk of thrombosis (low-risk PV). Among 20 patients with low-risk PV, 60.0% (12/20) and 85.0% (17/20) achieved < 45% hematocrit by weeks 24 and 52, respectively. The proportion of responders with complete hematologic response (CHR) was 60.0% (12/20) at we…

CRISPR-based rapid molecular diagnostic tests for fusion-driven leukemias.

Fusion oncogenes can be cancer-defining molecular alterations that are essential for diagnosis and therapy selection.1,2 Rapid and accessible molecular diagnostics for fusion-driven leukemias such as acute promyelocytic leukemia (APL), Philadelphia chromosome-positive acute lymphoblastic leukemia, and chronic myeloid leukemia (CML) are unavailable, creating a barrier to timely diagnosis and effective targeted therapy in many health care settings, including community hospitals and low-resource environments. We developed CRISPR-based RNA-fusion transcript detection assays using SHERLOCK (specifi…

Contribution of Mendelian Disorders in a Population-Based Pediatric Neurodegeneration Cohort.

OBJECTIVE: To evaluate Mendelian causes of neurodegenerative disorders in a cohort of pediatric patients. STUDY DESIGN: Patients enrolled in the Center for Applied Genomics Biobank at the Children's Hospital of Philadelphia with neurodegenerative symptoms were identified using an algorithm that consisted of including and excluding selected International Classification of Diseases, 9th and 10th edition codes. A manual chart review was then performed to abstract detailed clinical information. RESULTS: Of approximately 100 000 patients enrolled in the Center for Applied Genomics Biobank, 76 had…

Targets in MPNs and potential therapeutics.

Philadelphia-negative classical Myeloproliferative Neoplasms (MPNs), including Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF), are clonal hemopathies that emerge in the hematopoietic stem cell (HSC) compartment. MPN driver mutations are restricted to specific exons (14 and 12) of Janus kinase 2 (JAK2), thrombopoietin receptor (MPL/TPOR) and calreticulin (CALR) genes, are involved directly in clonal myeloproliferation and generate the MPN phenotype. As a result, an increased number of fully functional erythrocytes, platelets and leukocytes is observed in …

The roles of sex and genetics in the MPN.

The Philadelphia chromosome negative myeloproliferative neoplasms(MPNs), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are acquired hematopoietic stem cell disorders driven by activating mutations of intracellular signal transduction pathways that control the production of circulating blood cells. The MPN are characterized clinically by marked variation in degrees of vascular risk, familial clustering, and evolution to myelofibrosis and acute leukemia. MPN disease presentations and outcomes are highly variable, and are markedly influenced by both sex a…