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J R Matthews

Publications and source records attributed to J R Matthews.

At least 37 records · Page 2Linked to original sources
PubMed1993

Interaction of the C-terminal region of p105 with the nuclear localisation signal of p50 is required for inhibition of NF-kappa B DNA binding activity.

DNA binding of the homodimeric p50 subunit of NF-kappa B was inhibited by a bacterially expressed protein containing the ankyrin repeats present in the C-terminus of the p105 precursor but not by the I kappa B protein MAD-3. However p50 was retained on protein affinity matrices containing either the C-terminal ankyrin repeats of p105 or MAD-3. To investigate the interaction between p50 and proteins containing ankyrin repeats we have used a number of approaches to probe the accessibility of the p50 nuclear localisation signal in the protein complex. A monoclonal antibody recognising a linear epitope either very close to, or including, the nuclear localisation signal of the p50 protein could immunoprecipitate p50 homodimers but was unable to precipitate the protein when it was bound to the C-terminal region of p105. A close association between the nuclear localisation signal of p50 and the C-terminal region of p105 was also suggested by protease accessibility experiments. While the nuclear localisation signal of free p50 is extremely susceptible to cleavage with trypsin the same site is masked in the presence of the C-terminal ankyrin repeats of p105 and, to a lesser extent MAD-3. Removal of the nuclear localisation signal by trypsin digestion generates a protein that is fully competent for DNA binding but is refractile to inhibition by the C-terminal ankyrin repeats of p105. Addition of DNA destabilises complexes between p50 and ankyrin repeat containing proteins, increasing the susceptibility of the nuclear localisation signal to trypsin cleavage. The data suggest that there is a rapid exchange of p50 between complexes containing DNA or I kappa B proteins via a metastable complex containing DNA, p50 and I kappa B.

Amino Acid Sequence↗
PubMed1993

Role of cysteine62 in DNA recognition by the P50 subunit of NF-kappa B.

A powerful chemical modification procedure has been developed to define determinants of DNA recognition by the p50 subunit of NF-kappa B. Differential labelling with [14C] iodoacetate has identified a conserved cysteine residue, Cys62, that was protected from modification by the presence of an oligonucleotide containing the specific recognition site of the protein. To determine the importance of this cysteine residue, each of the conserved cysteines in p50 was changed to serine and the DNA binding properties of the mutant proteins determined. Scatchard analysis indicated that the C62S mutant bound to its DNA recognition site with a 10-fold larger dissociation constant than the wild type protein, while the other two mutants bound with an intermediate affinity. Dissociation rate constant measurements correlated well with the dissociation constants for the wild type, C119S, and C273S p50 proteins, whereas the p50 C62S-DNA complex dissociated anomalously quickly. Competition analyses with oligonucleotide variants of the DNA recognition site and nonspecific E. coli DNA revealed that the C62S p50 mutant had an altered DNA binding site specificity and was impaired in its ability to discriminate between specific and non-specific DNA. Thus the sulphydryl group of Cys62 is an important determinant of DNA recognition by the p50 subunit of NF-kappa B.

Amino Acid Sequence↗
PubMed1992

Thioredoxin regulates the DNA binding activity of NF-kappa B by reduction of a disulphide bond involving cysteine 62.

A role for redox regulation in activation of the NF-kappa B transcription factor was suggested by the observation that DNA binding activity of free protein, but not preformed DNA-protein complex, is inhibited by -SH modifying agents but enhanced by reducing agents. Mutagenesis of conserved cysteine residues in the p50 subunit identified amino acid 62 as being important for DNA binding, as a serine substitution at this position reduces DNA binding affinity, but renders the protein insensitive to -SH modifying agents. DNA binding activity of the wild type protein but not the amino acid 62 mutant was also stimulated by thioredoxin while detection of disulphide cross linked dimers in p50 but not the amino acid 62 mutant suggests that thioredoxin stimulates DNA binding by reduction of a disulphide bond involving cysteine 62. The physiological relevance of these findings was supported by the observation that cotransfection of a plasmid expressing human thioredoxin and an HIV LTR driven reporter construct resulted in an NF-kappa B dependent increase in expression of the reporter gene. Thus modification of p50 by thioredoxin, a gene induced by stimulation of T-lymphocytes in parallel with NF-kappa B translocation, is a likely step in the cascade of events leading to full NF-kappa B activation.

Amino Acid Sequence↗
PubMed1992

Parallel distributed processing and neuropsychology: a neural network model of Wisconsin Card Sorting and verbal fluency.

Neural networks can be used as a tool in the explanation of neuropsychological data. Using the Hebbian Learning Rule and other such principles as competition and modifiable interlevel feedback, researchers have successfully modeled a widely used neuropsychological test, the Wisconsin Card Sorting Test. One of these models is reviewed here and extended to a qualitative analysis of how verbal fluency might be modeled, which demonstrates the importance of accounting for the attentional components of both tests. Difficulties remain in programming sequential cognitive processes within a parallel distributed processing (PDP) framework and integrating exceedingly complex neuropsychological tests such as Proverbs. PDP neural network methodology offers neuropsychologists co-validation procedures within narrowly defined areas of reliability and validity.

Attention↗
PubMed1992

Failure of intensive chemotherapy in poor prognosis non-Hodgkin's lymphoma.

In an attempt to improve response and survival rates in patients with non-Hodgkin's lymphoma, a relatively intense six drug regimen MATCOP was developed comprising four-weekly cycles of methotrexate (100 mg/m2, IV, day 8), Adriamycin (30 mg/m2, IV, days 1,2), teniposide (75 mg/m2, IV, day 1), cyclophosphamide (300 mg/m2, po, days one to five), Oncovin (1.4 mg/m2, IV: maximum 2 mg, days 8, 15) and prednisolone (100 mg, po, days one to five). A randomised trial was conducted comparing MATCOP with the standard CHOP regimen, comprising three-weekly cycles of cyclophosphamide (750 mg/m2, IV, day 1), Adriamycin (50 mg/m2, IV, day 1), Oncovin (1.4 mg/m2 IV: maximum 2 mg, day 1) and prednisolone (100 mg, po, days two to six). Eighty patients with large cell lymphoma, diffuse mixed small cleaved and large cell lymphoma or diffuse small cleaved cell lymphoma were randomised, 47 to MATCOP and 33 to CHOP. MATCOP patients experienced increased granulocytopenia, thrombocytopenia (p less than 0.0001), mucositis (p = 0.002) and infections (p = 0.01) compared to CHOP patients. Complete response rates were similar: 66% for MATCOP patients and 61% for CHOP patients. There were no apparent differences in the time to relapse for patients achieving CR, the time to treatment failure or the overall survival time. Thus despite an increase in toxicity, the more intense regimen MATCOP failed to confer any therapeutic benefit compared with the standard CHOP regimen. Survival was not influenced but toxicity was increased by dose intensification.

Adolescent↗
PubMed1990

Effects of host age, host density and parent age on reproduction of the filth fly parasite Urolepis rufipes (Hymenoptera: Pteromalidae).

Urolepis rufipes Ashmead, a pteromalid wasp, was recently discovered parasitizing house fly and stable fly pupae in eastern Nebraska dairies. Studies have been conducted on the biology of this parasite to evaluate its potential as a biological control agent of stable flies (Stomoxys calcitrans (L.] and house flies (Musca domestica L.). House fly pupae were suitable as hosts for U.rufipes at all ages; however, significantly higher parasitism occurred on host pupae aged 96-120 h. Parasite-induced mortality (host mortality without progeny production) was higher than for other pteromalid parasites of filth flies under similar conditions. Parasitism increased with parasite--host ratio at 20 degrees C; however, the opposite was noted at 30 degrees C for parasite--host ratios ranging from 5:50 to 50:50. Fly eclosion decreased as parasite--host ratio increased at 20 degrees C, and no host eclosion occurred at the highest parasite--host ratios (20:50 and 50:50) at 30 degrees C. Females produced an average of 18.6 female and 7.6 male progeny. 88% of the progeny were produced during the first 6 days post parental eclosion. The short life span, low progeny emergence rate and high per cent host eclosion, in comparison with other parasite species, suggests that the Nebraska strain of U.rufipes may not an effective biological control agent of house flies.

Age Factors↗
PubMed1990

Interaction of enhancer-binding protein EBP1 (NF-kappa B) with the human immunodeficiency virus type 1 enhancer.

Human EBP1, isolated from HeLa cells, binds to a 10-base-pair (bp) sequence in cellular and viral enhancers that is also recognized by the inducible transcription factor NF-kappa B. Here we describe the interaction of purified EBP1 with the 10-bp repeated sequence that is responsive to signals which activate T cells and which form part of the human immunodeficiency virus type 1 (HIV-1) enhancer. DNase I footprinting indicates that both 10-bp sites on the same molecule, located between -80 and -105 on the HIV-1 long terminal repeat, can be occupied by EBP1, while dimethyl sulfate protection and methylation interference experiments indicate which purine bases are in contact with the protein. The presence of bases which exhibit increased rates of dimethyl sulfate-induced methylation in the presence of EBP1 indicate that interaction of EBP1 with its recognition site is accompanied by distortion of the DNA double helix. Supporting this conclusion is the observation that the polyamine spermidine dramatically increases EBP1 binding to its cognate site on the DNA. Studies with human T cells (Jurkat) and nucleotide stimulation data suggest that EBP1 is the activated form of NF-kappa B in these cells.

Base Sequence↗
PubMed1983

The question of stress among first-year medical students.

In a study reported in this article, the authors investigated the presence of stress in two successive classes of first-year medical students at a private midwestern medical school. Support groups, didactic sessions, and no-contact control conditions were used. Few differences in personality measures were found among the groups, and all group means were within the normal range. Support groups did not facilitate academic performance. The results bring into question the previously reported extent of chronic stress among students in the first year of medical school as well as the need for support groups in this population.

Anxiety↗
PubMed1981

Improved survival from acute lymphoblastic leukemia in adolescents and adults.

Nineteen adult patients with acute lymphoblastic leukemia were treated with combination chemotherapy to induce remission in the period from 1971 to 1979. Those patients achieving remission received intensive post-remission therapy with central nervous system (CNS) prophylaxis, followed by two-drug maintenance therapy, and reinduction courses of chemotherapy every six months. Remissions were achieved in 17 of the 19 patients (89%). Twelve patients (63%) are alive, 11 currently in complete remission. Two patients who experienced relapses in recent months have successfully undergone transplantation with allogeneic marrow from sex-matched, HLA-compatible sibling donors. The median survival and median duration rates of first remissions have not yet been reached, but to date are 36+ months and 29+ months, respectively with a predicted five-year survival rate of 61%. These results not only are significantly better than those achieved in the years 1968 to 1971 in our institution, but also are superior to others reported in the world medical literature. The combination of optimal treatment protocols with allogeneic marrow transplantation for patients with poor prognoses is expected to improve the survival of adult patients even further in the next decade.

Adolescent↗
PubMed1981

Comparison of 7 and 12 day bone marrow CFUc culture in adult acute non lymphoblastic leukaemia.

Bone marrows from 17 patients with acute nonlymphoblastic leukaemia (ANLL) were serially cultured on semisolid agar during periods of intensive remission induction chemotherapy and during remission. Of 12 patients achieving remission, six showed recovery of 7 and 12 day colony forming units (CFUc) culture to normal. However, in four of the six patients, recovery was short-lived with reappearance of typically leukaemic culture patterns while still in remission by bone marrow and peripheral blood criteria. In individual patients, serial 7 day cultures frequently showed persisting or recurring leukaemia-associated patterns while 12 day cultures were normal. This study confirms the heterogeneity observed in the cultural characteristics of the CFUc in acute non lymphoblastic leukaemia. Bone marrow cultures in patients with ANLL following intensive remission induction chemotherapy appear to provide a more reliable indication of persisting leukaemia or early relapse if they are interpreted earlier at 7 days.

Acute Disease↗
PubMed1980

Therapeutic plasmapheresis by continuous flow cnetrifugation.

This report reviews the experience at Auckland Hospital with continuous flow centrifugation as a mean of carrying out therapeutic plasmapheresis. Over a three year period from August 1975, 26 patients, most with dysproteinaemias or Goodpasture's syndrome, were treated with a total of 260 therapeutic procedures.

Adolescent↗
PubMed1980

Use of modified subcutaneous right-atrial catheter for venous access in leukaemic patients.

A large-diameter indwelling subcutaneous right-atrial catheter was inserted in 25 patients with haematological malignancies and neutropenia to provide ready access to the venous system for all infusions and blood aspirations. The median duration of catheter placement was 70 days. In 23 patients (92%) the catheter was used successfully until remission or death. Catheter-related exit-site infectons, generally mild, occurred in 14 patients (56%), Staphylococcus epidermidis being the predominant organism cultured. Septicaemia occurred in 11 neutropenic patients (44%). In 2 patients the same organism was grown from blood and exit site. The use of this catheter greatly facilitates patient care and support, minimises discomfort, and is associated with an acceptable rate of complications.

Acute Disease↗
PubMed1980

Bone marrow transplantation in a child with acute lymphoblastic leukaemia.

A caucasian female infant with acute lymphoblastic leukaemia in second remission received a bone marrow transplantation. Engraftment was confirmed at 14 days following infusion of bone marrow from a sex-matched, ABO and HLA compatible sibling. 171 days posttransplantation the patient is clinically well and in haematological remission. A mild transient skin rash and hepatocellular disturbance, the only manifestations of graft versus host disease, responded successfully to high dose prednisone.

Bone Marrow Transplantation↗