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M Nesbit

Publications and source records attributed to M Nesbit.

At least 55 records · Page 3Linked to original sources
PubMed1988

Mapping of three antigenic sites on the haemagglutinin-neuraminidase protein of Newcastle disease virus.

Nine neutralizing monoclonal antibodies (MAbs), each of which react with the haemagglutinin-neuraminidase (HN) glycoprotein of the Beaudette C strain of Newcastle disease virus (NDV), have been used in competitive binding assays to delineate three non-overlapping antigenic sites A, B and C. Epitopes within these sites have been identified on the basis of cross-reactivity of MAb-resistant mutants against the panel of MAbs, determined by plaque assays and Western blotting. Site A contains three non-overlapping epitopes (A1, A2 and A3). A1 is the only linear epitope; all remaining epitopes are conformational. MAbs which react with epitopes A2 and A3 inhibit neuraminidase activity (NA) when assayed with neuraminlactose. Site B contains three partially overlapping epitopes (B1, B2 and B3) and site C is represented by a single epitope (C1). HN gene sequence analysis of MAb-resistant mutants showed that they each had only single amino acid substitutions which range from amino acid residues 347-460 for site A, 284-325 for site B, and at 481 for the C1 epitope. The apparent molecular mass of the HN glycoprotein of one mutant was increased from 72 to 75 kDa. This correlates well with the creation of an additional potential glycosylation site in this mutant from Asn-Ser-Pro(325) to Asn-Ser-Ser(325).

Amino Acid Sequence↗
PubMed1988

Identification of haemagglutinin-neuraminidase antibody binding sites by Western blot analysis of antibody-resistant mutants and partial digest fragments of Newcastle disease virus.

A collection of monoclonal antibodies (MAbs) which react with the haemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) has been used to isolate MAb-resistant mutants of the Beaudette C strain of NDV. The patterns of cross-reactivity of the HN proteins of these mutants against the collection of MAbs determined by Western blotting allowed the MAbs to be sorted into different groups. Protease V8 partial digest fragments of purified wild-type virions and subsequent reaction against the collection of MAbs using Western blotting provided an alternative method of grouping MAbs which broadly agreed with the former method. Chemical cleavage of the HN protein at aspartate-proline bonds followed by Western blotting of the fragments allowed the approximate position of certain MAb binding sites to be determined.

Antibodies, Monoclonal↗
PubMed1988

Location of a neutralizing epitope for the haemagglutinin-neuraminidase glycoprotein of Newcastle disease virus.

The binding site of a monoclonal antibody to the haemagglutinin-neuraminidase (HN) polypeptide of Newcastle disease virus (NDV) has been located. Complementary DNA or synthetic oligonucleotides corresponding to portions of the HN gene were cloned into the Escherichia coli vector pUC19 and fragments of the HN protein were thereby fused to the alpha-peptide of beta-galactosidase. Western blot analysis of E. coli lysates containing expressed fragments of the HN cDNA or synthetic oligonucleotides identified an antibody-binding peptide (Asp-Glu-Gln-Asp-Tyr-Gln-Ile-Arg; amino acid residues 346 to 353). Nucleotide sequence analysis of an antibody-resistant mutant of NDV revealed a Glu (wild-type) to Lys (mutant) substitution within the above sequence. The methods described could be useful for the location of continuous epitopes of other polypeptides.

Animals↗
PubMed1986

Analysis of prognostic factors in acute lymphoblastic leukemia.

Children with ALL who have a high probability of excellent response, long-term survival, and cure when treated with widely available standard therapy can be identified at the time of diagnosis. Others can be identified who are at high risk of failure to respond, early relapse, and death. The importance of such prognostic characteristics is so great that they should be considered in the selection of appropriate treatment for each patient. Prognostic factors also must be considered in the design and analysis of clinical trials. All prognostic factors are not equally significant and many of them are closely associated. It is possible to rank them in importance and usefulness by appropriate statistical methods. As additional prognostic factors are identified, and as more effective and more specific therapies are developed, the relative importance of prognostic factors will change.

Adolescent↗
PubMed1985

Local recurrence, rate and sites of metastases, and time to relapse as a function of treatment regimen, size of primary and surgical history in 62 patients presenting with non-metastatic Ewing's sarcoma of the pelvic bones.

This report reviews the experience of 62 patients who presented between 1972 and 1978 with non-metastatic Ewing's sarcoma of the pelvis and were entered on IESS I. Seventeen patients (27%) developed a local recurrence, 38 patients (61%) demonstrated metastases and 21 (34%) neither. In the dose range 4000 rad to 6000 rad no dose response could be detected for local control of tumor. Forty-six patients (74%) had a biopsy or exploratory surgery only, 5 patients (8%) had an incomplete resection and 11 patients (18%) had a complete resection of their tumor. In the 46 patients having a biopsy only, 13 developed a local recurrence (28%) as compared to 2 of 11 patients undergoing a complete resection (18%). The most common sites for metastases were lung in 19 patients (31%) and bone in 23 patients (37%). No significant difference was noted in the frequency of overall metastases or metastases to any site between those patients receiving one of the three treatment regimens used in IESS I: VAC and Adriamycin (regimen I), VAC alone (regimen II) and VAC plus bilateral pulmonary irradiation (regimen III). At a median follow-up of 135 weeks no significant difference in median survival could be detected in patients with pelvic primaries between regimens I, II and III. The mean diameter of the pelvic primaries was comparable to the nonpelvic, however, one half of the pelvic cases were in the range 10-15 cm. The median time to relapse of the 241 non-pelvic patients on IESS I was 222 weeks as contrasted with the median time to relapse of 92 weeks in the 62 pelvic patients on the same study (p = 0.002). The possible reasons for the poor prognosis of pelvic primary patients are discussed together with treatment policies that might improve the survival of this group of patients.

Adolescent↗
PubMed1985

Second malignant neoplasms in children: an update from the Late Effects Study Group.

This paper presents an update from the Late Effects Study Group on 292 cases of second malignant neoplasms (SMN) occurring in individuals who were diagnosed with their first neoplasm in childhood. Data are presented regarding the types of first and second neoplasm, the therapy administered, and the predisposing factors. Of the 292 cases (308 SMN), the most common primary was retinoblastoma followed by Hodgkin's disease, soft-tissue sarcomas, and Wilms' tumor. This is not similar to the relative frequency of these cancers in children but rather reflects specific risk factors. Bone sarcomas were the most common SMN among the 208 SMN developing in previously irradiated sites while acute leukemia was the most common SMN unassociated with radiation. Known predisposing conditions to cancer were present in 73 cases; retinoblastoma was the most common of these, followed by neurofibromatosis. There were ten patients with three and three patients with four malignant neoplasms. In 14 patients, the cause of SMN was not suggested by known risk factors as these patients had negative family histories and received no radiation or chemotherapy. We note, therefore, that although most cases of SMN in survivors of childhood cancer can be attributed to radiation, genetic disease, chemotherapy, or combinations of these, unrecognized predisposition or chance may also play a role.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Bone marrow transplantation for acute nonlymphocytic leukemia in first remission: analysis of prognostic factors.

Prognostic factors were reviewed retrospectively for 39 children and adults aged 1 to 40 years (median 14 years) with acute nonlymphocytic leukemia (ANLL) who attained a first remission and underwent bone marrow transplantation from November 1976 to July 1983. The preparation regimen for transplantation was cyclophosphamide (60 mg/kg/d for two days) followed by total body irradiation (either 750 cGy single dose at 26 cGy/min, n = 37, or 1,320 cGy fractionated at 10 cGy/min, n = 2). Twenty-three patients are surviving disease free with a median followup of three years. The three-year estimated disease-free survival is 55% +/- 17% (+/- 2 SE). Five patients have relapsed from 92 to 756 days after transplantation for an estimated relapse rate of 21% +/- 18%. Two factors, the white blood cell (WBC) count and the French-American-British (FAB) classification at leukemia diagnosis were found to be of prognostic importance. Patients with a WBC of less than 20,000/microL at diagnosis had a three-year estimated disease-free survival of 74% +/- 18% v 26% +/- 24% for those with a WBC of greater than or equal to 20,000 (P = .008). The estimated relapse rate was 6% +/- 12% for patients with a WBC at diagnosis less than 20,000 v 53% +/- 38% for patients with a WBC at diagnosis of greater than or equal to 20,000 (P = .01). Patients with myeloid morphology at diagnosis (FAB M1,2,3) had an estimated relapse rate of 9% +/- 12% v patients with monocytoid morphology (FAB M4,5a) whose estimated relapse rate was 58% +/- 44% (P = .05). Our data suggest that a high WBC count at poor prognostic factors for patients with ANLL who undergo bone marrow transplantation in first remission after conditioning with cyclophosphamide plus total body irradiation.

Acute Disease↗
PubMed1985

Autologous bone marrow transplantation for patients with acute lymphoblastic leukemia in second or subsequent remission: results of bone marrow treated with monoclonal antibodies BA-1, BA-2, and BA-3 plus complement.

Autologous bone marrow transplantation (BMT) was utilized as therapy for 23 patients with acute lymphoblastic leukemia (ALL) in second or greater remission. Bone marrow was treated in vitro with a combination of monoclonal antibodies, consisting of BA-1, BA-2, BA-3, and baby rabbit complement (BRC'). All patients were prepared for transplantation with cyclophosphamide and fractionated total body irradiation. Engraftment occurred in all 23 patients. Seven of 23 patients remain relapse-free from six to 32 months (median, 21.4 months) posttransplant. Failures were due to relapse with the exception of one patient who died of infection. This study demonstrates that autologous BMT using in vitro marrow treatment with BA-1, BA-2, BA-3, and BRC' is safe, allows engraftment, and results in prolonged survival for some patients with ALL in second or greater remission.

Adolescent↗
PubMed1983

Bone marrow involvement in histiocytosis X.

Twenty-eight patients with histiocytosis X (HX) who had bone marrow aspirates and/or trephine biopsies taken at diagnosis were studied. Five of the 28 patients (18%) had bone marrow specimens with clusters of benign histiocytes characteristic of histiocytosis X. Several statistically significant clinical and laboratory differences were found between those patients with positive marrows versus those with uninvolved bone marrows. Presence of HX in the bone marrow was more frequently associated with fever (P less than 0.01), splenomegaly (P less than 0.01), rash (P = 0.04), diabetes insipidus (P = 0.09), and platelet counts less than 175 X 10(9)/L(P = 0.01). Two of the five patients with bone marrow involvement died, whereas there were no deaths due to HX in the other 23 patients. From this review, it is suggested that bone marrow involvement at diagnosis may be associated with more extensive and potentially fatal disease. HX of the marrow was more easily diagnosed from trephine biopsy sections than aspiration smears.

Adolescent↗
PubMed1983

Thyroid neoplasm after high-dose radiotherapy.

A female patient is described who developed papillary-follicular carcinoma of the thyroid 8 years after receiving high-dose external radiotherapy to the head and neck. This malignant neoplasm developed while she was taking suppressive doses of thyroid medication. Although it has long been thought that high-dose radiotherapy is not associated with the occurrence of thyroid tumor, it is becoming increasingly apparent that this concept is not necessarily true. Clinicians should be aware of the possible sequelae of neoplastic thyroid disease after any amount of external radiotherapy to the head and neck. Careful periodic follow-up of patients who have received such treatment is strongly advised.

Adenocarcinoma↗
PubMed1982

Clinical usefulness of monoclonal-antibody phenotyping in childhood acute lymphoblastic leukemia.

Lymphoblasts from 59 children with non-T, non-B acute lymphoblastic leukaemia were studied with monoclonal antibodies to four cell-surface proteins. 87% of the children had lymphoblasts positive for HLA-DR, 82% for p30, 75% for p24, and 72% for CALLA. The commonest composite phenotype was HLA-DR+ p30+ CALLA+ p24+. Significant correlations were seen between expression of HLA-DR, p30, and CALLA, but not p24. p30- and CALLA phenotypes were found in patients with high white-blood-cell counts (WBC) and splenomegaly. With standard chemotherapy, disease-free survival from time of remission was shorter in p30- and CALLA- patients than in others. Splenomegaly was associated with poor disease-free survival and provided prognostic information independent of phenotype. High WBC was less significant than phenotype in predicting outcome and was not independent of phenotype.

Adolescent↗
PubMed1981

Disappearance of the predictive value of prognostic variables in childhood acute lymphoblastic leukemia: a report from Childrens Cancer Study Group.

The identification of important prognostic factors at diagnosis of childhood leukemia has been very useful in explaining the marked differences in disease outcome. After a complete remission is achieved, it is interesting to determine whether the ability to maintain a complete remission and the patient's survival continue to be influenced by the prognostic factors identified at diagnosis. If the maintenance of complete remission and survival continue to be influenced, it is important to determine the magnitude of this effect and its variations with time. Data from a study population of 936 children with newly diagnosed acute lymphoblastic leukemia were analyzed to determine the duration of effect for three variables showing strong prognostic influence: WBC, age at diagnosis, and sex. The strongest of these, WBC, showed a gradual attenuation of effect for children in progressively longer periods of complete continuous remission to a virtual disappearance at 24 months. Age and sex showed a similar reduction in prognostic effect with a negligible contribution at 15 months of continuous complete remission. However, sex becomes an important variables again with a late effect on recurrence results in patients who experience long periods of remission.

Adolescent↗