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B L Weber

Publications and source records attributed to B L Weber.

113 records · Page 7Linked to original sources
PubMed1988

Phospholipase C activates protein kinase C and induces monocytic differentiation of HL-60 cells.

Phospholipase C (PLC)-mediated hydrolysis of membrane phospholipids results in the production of diacylglycerol, inositol phosphates, and choline metabolites. Inositol triphosphate increases calcium levels, while diacylglycerol activates protein kinase C. The present studies demonstrate that exogenous PLC generates inositol phosphates, releases choline metabolites, and activates protein kinase C in human HL-60 promyelocytic leukemia cells. PLC also induced monocytic differentiation of HL-60 cells as manifested by adherence, growth inhibition, and appearance of monocytic cell surface antigens. Furthermore, PLC treatment decreased c-myc mRNA levels and induced c-fos, c-fms, and tumor necrosis factor transcripts. The changes in gene expression induced by PLC are similar to those previously shown to be associated with phorbol ester-induced monocytic differentiation of HL-60 cells. Our results thus demonstrate that exogenous PLC activates HL-60 cell protein kinase C and that this effect is associated with induction of monocytic differentiation. PLC may therefore play a role in transducing signals from physiological inducers of monocytic differentiation.

Cell Differentiation↗
PubMed1987

Transient acute hepatotoxicity of high-dose methotrexate therapy during childhood.

Serial liver-enzyme determinations were performed on 36 children with acute lymphoblastic leukemia who were randomized to receive either conventional intrathecal methotrexate (MTX) therapy with cranial irradiation, or an investigational high-dose MTX regimen consisting of 10 courses of 33,600 mg/m2 over 24 hours, with high-dose leucovorin rescue. Both groups of patients received intermittent low-dose oral MTX during maintenance therapy. Serum transaminase elevations in the group of conventionally treated patients were infrequent and moderate in severity (less than 300 IU/liter). In the investigational group, however, the majority of patients had severe, acute increases in SGPT (greater than 300 IU/liter), with peaks up to 1000 to 2000 IU/liter. The incidence and severity of acute transaminasemia were directly proportional to the number of high-dose MTX courses received: courses 1, 2, 3, 4, 5, and 6 caused transaminase elevations in 31%, 50%, 50%, 73%, 100%, and 100% of courses, respectively, and 0%, 14%, 20%, 44%, 55%, and 92%, respectively, were over 300 IU/liter. Patients in both treatment groups developed a pattern of increasing serum alkaline phosphatase concentrations after initiation of low-dose oral MTX therapy; isoenzyme analysis indicated that this effect was osseous rather than hepatic. Serum bilirubin was rarely elevated. Transaminases returned to normal within 1 to 2 weeks after each high-dose MTX treatment, and with follow-up for as long as 7 years, no patient has developed clinical evidence of residual liver disease, after 3 years of high-dose MTX therapy and multiple other antileukemia drugs. The acute hypertransaminasemia frequently observed after high-dose MTX therapy is transient and reversible, and, in children, does not appear to result in chronic liver disease.

Adolescent↗
PubMed1981

Malignant melanoma: a search for occult lymph node metastases.

Lymph nodes regarded as "negative" following routine pathologic examination were reexamined in seven patients with malignant melanoma who later developed systemic metastases. A total of 185 lymph nodes were serially sectioned; five to seven levels of each lymph node were examined for the presence of occult metastases. In this manner previously undetected tumor was found within a solitary lymph node of one patient. It is concluded that attempts to detect occult melanoma metastases by routine serial sectioning of lymph nodes is not of practical applicability.

Adolescent↗
PubMedDate not supplied

Establishing a cancer risk evaluation program.

PURPOSE: Presymptomatic genetic testing for cancer susceptibility is a new practice arena that raises many complex issues. This article presents one model of a cancer risk evaluation program that specifically addresses the unique issues associated with genetic testing for cancer risk. DESCRIPTION OF PROGRAM: The Cancer Risk Evaluation Program is designed to care for any individual concerned about his or her risk for cancer, offering predisposition genetic testing if appropriate. The program includes clinical and psychosocial assessment, education, cancer risk analysis, and genetic counseling; it offers long-term screening and surveillance and provides a forum for ongoing genetic and clinical research. RESULTS: Program evaluations from participants have shown that the program is successfully meeting the needs of the participants. This program also ensures that the University of Pennsylvania Cancer Center is delivering cancer genetic services consistent with the existing position statements on genetic testing for cancer susceptibility, which have included guidelines and indications for predisposition genetic testing and informed consent. CLINICAL IMPLICATIONS: Researchers anticipate a substantial demand for predisposition genetic testing for cancer susceptibility. However, not all individuals interested in testing are eligible or willing to undergo direct gene analysis because of the potential risks. Therefore, clinical programs must address the complex issues surrounding presymptomatic genetic testing and incorporate cancer risk assessment strategies. Additionally, healthcare providers in this new practice arena should be fully informed and current in the state of the knowledge regarding cancer risk assessment; predisposition genetic testing; and the ethical, legal, and social issues pertaining to cancer risk assessment and management.

Adult↗