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Biomedical subjects

P Major

Publications and source records attributed to P Major.

At least 55 records · Page 3Linked to original sources
PubMed1983

Biologic effect of 5-fluoro-2'-deoxyuridine incorporation in L1210 deoxyribonucleic acid.

Recent studies have demonstrated that 5-fluoro-2'-deoxyuridine (FdUrd) misincorporates in eukaryotic DNA. We have extended these findings and studied the relationship between DNA incorporation of FdUrd and cell lethality. This required an approach that would distinguish the DNA and RNA effects of this agent. The specific effect of (FdUrd)DNA formation on L1210 clonogenic survival was, therefore, monitored using deoxyuridine (dUrd) to inhibit the metabolism and subsequent incorporation of FdUrd into RNA. The results demonstrated that misincorporation of FdUrd in DNA resulted in lethal cellular events. These observations suggest a new mechanism of action for this cytotoxic and mutagenic agent.

Animals↗
PubMed1983

A phase I-II study of combination therapy with thymidine and cytosine arabinoside.

Twenty-one patients with leukemia and lymphoma refractory to conventional therapy were treated with thymidine (dThd) at a dose of 75 g/m2/day for 48 h by continuous intravenous (IV) infusion, followed by cytosine arabinoside (ara-C) on an escalating dose schedule of 25-625 mg/m2/day for 48 h by continuous IV infusion. Toxicity included somnolence (1 patient), mucositis (2 patients), and myelosuppression (19 patients). One patient died prior to completion of therapy. Because of the patient population studied (mainly consisting of patients with leukemia refractory to conventional therapy) and the prevalence of myelosuppression prior to therapy, a median toxic dose was not evaluable. Therapeutic responses included a partial remission in a patient with acute myelogenous leukemia (AML) refractory to ara-C. An additional six patients with acute leukemia refractory to ara-C transiently cleared their peripheral blood of blasts, and a decrease in circulating blasts was noted in two other patients. Biochemical studies conducted on the peripheral blasts of two patients confirmed an enhancement by dThd of the incorporation of ara-C into the DNA of circulating blasts.

Adolescent↗
PubMed1983

Generation time of leukaemic blast progenitor cells.

Previous studies have indicated that the generation time of human leukaemic cells is longer than that of normal haematopoietic cells. We have employed a modification of the thymidine (TdR)-suicide technique to measure directly the generation time of leukaemic progenitor cells capable of colony formation. The results obtained with two human leukaemic cell lines (KG-1 and HL-60) and with blast progenitor cells from two patients with acute myelogenous leukaemia indicate generation times ranging from 9 X 0-22 X 0 hr and S-phase durations ranging from 5 X 5-8 X 0 hr. Using the same technique, the generation time of normal bone marrow CFU-c was determined to be 9-11 hr. These findings suggest that the proliferation rate of human leukaemic blast progenitor cells is similar to that of normal haematopoietic stem cells.

Adolescent↗
PubMed1982

Induction of differentiation of human myeloid leukemia cells by inhibitors of DNA synthesis.

The HL-60 human leukemic promyelocyte can be induced to mature into terminally differentiated cells using certain nucleosides and chemotherapeutic agents. The mechanisms responsible for this induction of differentiation, however, remain unclear. We have monitored the effects of two specific inhibitors of DNA synthesis to determine whether slowing of DNA polymerization can induce HL-60 differentiation. The results demonstrate that cytosine arabinoside (ara-C) induces nonspecific esterase activity in HL-60 cells and increases surface expression of the monocyte antigen MY-4. The results also demonstrate that aphidicolin, an inhibitor of DNA polymerase which is not incorporated in DNA, induces similar phenotypic changes. The induction of differentiation by both agents was accompanied by loss of clonogenic potential as monitored by colony formation in methylcellulose. These observations suggest that terminal differentiation of HL-60 cells can be induced by drugs known to inhibit DNA synthesis.

Aphidicolin↗
PubMed1981

Effect of high-dose thymidine infusions in patients with mycosis fungoides.

The antitumor effect of thymidine has been demonstrated in patients with leukemia and lymphoma. This report summarizes the treatment of three patients with mycosis fungoides, a chronic T-cell lymphoma. Four courses of thymidine (75 g/m2/day) were administered by continuous infusion for 4-7 days. Steady-state serum thymidine levels were in the range of 1-3 mM. Associated toxicities were minimal and consisted of milk headache and anorexia. Myelosuppression was manifested by transient declines in the peripheral leukocyte count. One patient had extensive clearing of diffuse erythematous plaques on the trunk and extremities that persisted for over one month. A second patient had partial clearing of plaques that persisted for two weeks following therapy and a third patient had a minimal response with 25% reduction in lymphadenopathy and noduloulcerative lesions. These responses indicate the effectiveness of thymidine as a single agent in the treatment of mycosis fungoides.

Aged↗
PubMed1981

A simple procedure for isolation and purification of A-type staphylococcus enterotoxin.

A new procedure is presented for the isolation and purification of A-type staphylococcus enterotoxin. Homogeneous enterotoxin preparation was obtained by purification in 2 phases. In radial double agar-gel immunodiffusion the smallest precipitating dose of the isolated and purified enterotoxin was found to be 1.4-0.7 micrograms protein and 0.4-0.1 micrograms nitrogen. In cat experiments the dose giving a positive reaction was 2 micrograms protein or 0.5 micrograms nitrogen calculated for kg body weight.

Ammonium Sulfate↗
PubMed1981

Treatment of central nervous system tumors with methotrexate.

Thirteen patients with primary and metastatic CNS tumors have been treated with methotrexate (MTX) using three different approaches: (a) high-dose MTX with leucovorin (LV) rescue; (b) high-dose MTX with carboxypeptidase (CPDG) rescue; and (c) intraventricular administration of low doses of MTX for extended periods (concentration X time [CXT]). Eleven patients had central nervous system (CNS) lymphoma (one primary, one patient had recurrent medulloblastoma, and another patient had metastatic breast carcinoma. All 13 patients received high-dose MTX-LV rescue, while 3 patients were subsequently given MTX-CPDG. One patient received MTX by all three modalities. In patients with CNS lymphomas, complete responses (45%) and partial responses (36%) produced CNS disease-free intervals ranging from 1 to 23+ months. Survival for the complete responders has thus far ranged from 2.5 to 35 months, while the partial responders survived from 3 to 5 months. Two patients failed to respond and survived 2.5 and 3 months. Responses were obtainable with high-dose MTX-CPDG in patients resistant to MTX-LV. One patient who became sensitized to CPDG subsequently responded to MTX by intraventricular CXT administration. Thus, MTX can be effectively administered to patients with CNS tumors by several different approaches.

Adolescent↗
PubMed1980

Heterotopic ossification in paraplegia: a possible disturbance of the paravertebral venous plexus.

The distribution of the heterotopic ossifications that complicate paraplegia and other neurological disorders is remarkably similar to that of the paravertebral venous plexus of Batson. Stasis within this system consequent to immobilization and spinal trauma, combined with demineralization of the skeleton, are postulated to be the main factors promoting precipitation of calcium salts in the soft tissues in these conditions.

Humans↗
PubMed1979

Quantitative determination of staphylococcal B-type enterotoxin with Laurell's electroimmune diffusion method.

The quantitative determination of B-type enterotoxin produced by Staphylococcus aureus is described. Pretreating the toxin with formaldehyde, the B-type enterotoxin could be demonstrated rapidly with appropriate sensitivity by Laurell's electroimmune diffusion method. Four to eight hours were required for the examination and 0.25 microgram/ml was the smallest demonstrable quantity of the toxin.

Enterotoxins↗
PubMed1978

Selective hypopituitarism with severe hyponatremia and secondary hyporeninism.

A female patient presenting clinically a severe hyponatremia was found to have a selective hypopituitarism with predominant ACTH and partial FSH, LH, and GH deficiency as well as a suppression of plasma renin activity and aldosterone. The adrenal cortex responded well in cortisol increase to ACTH infusion and in plasma aldosterone increase to angiotensin II infusion. The patient had pressor hyperreactivity to angiotensin II. The hyponatremia was caused by a negative sodium balance induced by excessive urinary loss which remained unaffected by mineralocorticoid treatment. Substitution doses of cortisol, however, corrected the disturbance with an increase in plasma renin activity and improvement in the sodium balance. The data are interpreted as indicating a direct or indirect regulatory (permissive?) effect of low doses of cortisol on plasma renin activity correcting the underlying disturbance--the secondary hyporeninism.

Adrenocorticotropic Hormone↗
PubMed1978

Analysis of the semantic structures of medical reference languages: part 2. Analysis of the semantic power of MeSH, ICD and SNOMED.

Three medical reference languages, Medical Subject Headings (MeSH), International Classification of Diseases (ICD) and Systematized Nomenclature of Medicine (SNOMED), were compared through an analysis of their structures. They were found to differ in the degrees of complexity and specificity of meaning that they could convey. This variation in semantic power has been correlated with their different functions.

Classification↗