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Biomedical subjects

J M Carter

Publications and source records attributed to J M Carter.

At least 109 records · Page 6Linked to original sources
PubMed1988

Use of synthetic peptides to identify an N-terminal epitope on mouse gamma interferon that may be involved in function.

We previously have assigned N-terminal specificity to three hamster monoclonal antibodies (mAbs I, II, and III) produced to mouse recombinant gamma interferon (IFN-gamma), based on the ability of the N-terminal peptide IFN-gamma-(1-39) to block binding of 125I-labeled IFN-gamma (125I-IFN-gamma) and on the ability of these antibodies to bind 125I-IFN-gamma-(1-39). Only mAb I blocked function and binding to the IFN-gamma receptor, suggesting that it may bind to a region of the molecule involved in interaction with the receptor. To further define the epitope specificities of the antibodies, a series of N-terminal peptides were synthesized and tested for their ability to block antibody binding of 125I-IFN-gamma. Peptides IFN-gamma-(1-39), IFN-gamma-(1-20), IFN-gamma-(3-20), and IFN-gamma-(5-20) inhibited binding of 125I-IFN-gamma by mAb I in order of decreasing effectiveness, while peptide IFN-gamma-(7-20) was without effect. Peptides IFN-gamma-(1-39), IFN-gamma-(1-20), and IFN-gamma-(3-20) also inhibited binding of 125I-IFN-gamma by mAb II but were less effective when compared with their inhibition of mAb I. IFN-gamma-(5-20) and IFN-gamma-(7-20) did not inhibit binding by mAb II. Peptides IFN-gamma-(1-10), IFN-gamma-(10-30), and IFN-gamma-(21-44) did not inhibit either mAb I or mAb II. While IFN-gamma-(1-39) and IFN-gamma-(10-30) inhibited binding by mAb III, neither IFN-gamma-(1-20) nor any of its truncated forms were inhibitory. All three antibodies had similar Kd values for 125I-IFN-gamma. A prediction of the secondary structure of the molecule and the peptide inhibition data suggest that the epitope (possible receptor binding region) for mAb I involves a loop in the area containing residues 12-20, with sequences N-terminal to these residues possibly stabilizing the loop conformation. Direct evidence that the N-terminal 1-39 region of IFN-gamma is important in receptor binding was the observation that IFN-gamma-(1-39), but not the C-terminal IFN-gamma-(95-133), competed with 125I-IFN-gamma for the receptor on mouse L cells. IFN-gamma-(1-39) also specifically blocked IFN-gamma antiviral activity at concentrations that blocked binding to the receptor. The fact that IFN-gamma-(1-39) was the only peptide that blocked both IFN-gamma binding to receptor and function is consistent with the antibody competition data, where it was the most effective peptide in blocking binding of 125I-IFN-gamma by the N-terminal-specific mAbs. The combination of peptide mapping of epitope specificities and receptor competition should further help define the structural basis for IFN-gamma action.

Animals↗
PubMed1988

The haematology of hyperthyroidism: abnormalities of erythrocytes, leucocytes, thrombocytes and haemostasis.

The abnormalities of erythrocytes, leucocytes, thrombocytes and coagulation that have been reported, particularly in more recent years, to be associated with hyperthyroidism are surveyed. Several areas are highlighted where further investigations could lead to clinically useful insights, improved information about the haematological processes involved or to a better understanding of thyroid hormone action.

Blood Cells↗
PubMed1988

Effects of recombinant human erythropoietin on megakaryocytes and on platelet production in the rat.

The contention that erythropoietin (Epo) affects platelet production was investigated in the rat with recombinant human Epo (rHuEpo). In normal rats, Epo caused a dose-dependent increase in both reticulocyte and platelet numbers, the reticulocyte response preceding that of platelets. Withdrawal of Epo resulted in reticulocytes and platelets returning to control levels. [75Se]-selenomethionine incorporation into platelets was also enhanced in response to Epo. Chronic daily administration of rHuEpo resulted in steady state erythrocyte levels after 12 to 14 days, which were elevated 20% above controls. Attainment of this steady state was associated with both reticulocytes and platelets returning to control levels despite continued administration of Epo, an effect not associated with a change in the half-life of circulating Epo. In polycythemic rats a platelet response was observed before an effect on reticulocytes. Erythropoietin caused a 2.4-fold increase in the frequency of small acetylcholinesterase-positive cells within 24 hours, and increased the mean megakaryocyte diameter within 48 hours. Furthermore, the [3H]-thymidine labeling index of megakaryocytes from rats treated for 24 hours with rHuEpo was increased for all stages of megakaryocyte maturation. These results support the proposal of an effect of Epo on rat megakaryocytes causing increased platelet production.

Animals↗
PubMed1988

CREST syndrome: a variant of progressive systemic sclerosis, associated with interstitial pulmonary fibrosis and malignancy.

We have described a patient who had a clinical picture of CREST syndrome and pulmonary interstitial fibrosis, and in whom adenocarcinoma of the lung developed over a four-year period. Despite absence in the literature of the association of lung carcinoma in patients with CREST syndrome, our case is an example of pulmonary fibrosis complicated by lung cancer without any evidence of other risk factors. We believe this to be the first report of such an association. Clinicians, therefore, must be aware that pulmonary interstitial fibrosis in patients with the CREST syndrome may represent a risk for lung cancer.

Adenocarcinoma↗
PubMed1987

Transfusion related HIV infection: the Wellington experience.

A case of transfusion-related AIDS is described which is believed to be the first published case to occur in New Zealand in a nonhaemophiliac patient. The human immunodeficiency virus (HIV) positive donor was shown to be the source of infection in five further HIV positive recipients.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Pigmentary demarcation lines: a population survey.

An examination of 380 patients was accomplished in order to determine the frequency of occurrence of pigmentary demarcation lines in an unselected population. Both white and black patients were included in the study, and there was an equal sex distribution. Separation of data by age groups enabled us to determine that the age of onset is in early childhood in the majority of cases. Seventy-nine percent of black female adults have at least one type of pigmentary demarcation line, with types A and B being present in over 50% of the cases. Seventy-five percent of black male patients had at least one pigmentary demarcation line, with type C being most prevalent. Fifteen percent of white female patients had one pigmentary demarcation line. Finally, it was determined that seven of fifty black women (14%) had the new appearance of type B lines with pregnancy.

Adolescent↗
PubMed1987

The suppression of acute corneal inflammation by Bredinin.

This study tested the effect of Bredinin, a nucleoside antibiotic of fungal origin, on experimentally induced acute inflammation of the rabbit cornea. Inflammation was produced by abrasive removal of a 9 mm disk of corneal epithelium. In the dose-response experiments, one eye of each rabbit was treated topically with Bredinin, and the other eye with vehicle immediately after deepithelialization. The acute inflammatory leukocytes in tear film samples were counted at various times and the corneas were examined histologically at the end of the study. A paired t-test revealed that the numbers of acute inflammatory leukocytes after 5 hours were significantly less in the Bredinin-treated eyes, compared with the untreated eyes. The timing of drug-treatment was important; Bredinin was most effective in suppressing acute ocular inflammation when administered at, or within, one hour of the inflammatory stimulus. Histologic analysis demonstrated fewer acute inflammatory leukocytes on the ocular surface and in the stroma of the Bredinin-treated eyes, compared with the untreated eyes. No obvious corneal toxicity was noted, and the drug-treated eyes appeared less inflamed than the control eyes. The results of this study demonstrate the capacity of Bredinin to suppress the entry of inflammatory leukocytes into the tear film and suggest that this drug may have potential for use as a topical anti-inflammatory agent.

Acute Disease↗
PubMed1987

Extracorporeal membrane oxygenation and high-frequency oscillatory ventilation: potential therapeutic relationships.

Eighteen neonates 33 to 42 wk gestational age with severe respiratory failure were referred for extracorporeal membrane oxygenation (ECMO). Sixteen ultimately met the ECMO criteria, of whom 15 were first offered high-frequency oscillatory ventilation (HFOV). Seven responded to HFOV alone and did not require ECMO treatment. Eight of the nine remaining patients were placed on ECMO support with HOFV. Infants who responded to HFOV alone tended to have pneumonia more than meconium aspiration, to be smaller and more immature, to have higher Apgar scores, and to have suffered severe hypoxia (alveolar-arterial oxygen pressure difference over 600 torr) for less time than the ECMO group. Although patient numbers are small, a trend is noted which favors HFOV treatment alone in terms of the duration of HFOV, the total duration of assisted ventilation, the rapidity with which extubation was accomplished, and the length of hospital stay.

Birth Weight↗
PubMed1986

Interstitial pneumonitis due to leukaemic cell necrosis.

Pulmonary complications are common in patients with acute leukaemia. Infection is the usual cause of these. A case of acute leukaemia is described in which diffuse interstitial pneumonitis developed during remission induction therapy. This occurred during a very rapid fall in the leukaemic blast population following the start of chemotherapy. Open lung biopsy showed necrotic leukaemic cells filling the lung interstitium. The patient made an uneventful recovery from this complication.

Adult↗
PubMed1986

Use of the deoxyuridine suppression test to evaluate vitamin B12 and folate status.

The deoxyuridine suppression test (DUST), performed on bone marrow cells, or peripheral blood lymphocytes, provides a rapid, dynamic assessment of vitamin B12 and folate status. The principles of this test are described and the use of the DUST in haematological practice at Wellington Hospital is reviewed. The advantages of the test are the speed of obtaining results, and an accurate assessment of the patient's condition when other haematological tests may be misleading.

Anemia↗
PubMed1986

Epitope and functional specificity of monoclonal antibodies to mouse interferon-gamma: the synthetic peptide approach.

Spleen cells from hamsters immunized with recombinant mouse interferon-gamma (IFN-gamma) were fused with mouse myeloma cells, resulting in the production of four anti-IFN-gamma monoclonal antibodies. Binding of 125I-IFN-gamma by these protein A-bound antibodies was specifically blocked by cold IFN-gamma. Binding by three of these antibodies was also blocked by a synthetic peptide corresponding to the N-terminal 1-39 amino acids of IFN-gamma, whereas a corresponding C-terminal (95-133) peptide had no effect on binding. The N-terminal specificity of these three antibodies was confirmed by their specific binding of 125I-N-terminal (1-39) peptide. One of the N-terminal specific monoclonal antibodies inhibited both antiviral and macrophage priming (for tumor cell killing) activities of IFN-gamma, whereas the other two had no effect on either biologic function. The selectivity of the inhibition of IFN-gamma function was not due to a differential ability of the N-terminal specific antibodies to bind IFN-gamma. Blocking experiments with cold IFN-gamma and N-terminal peptide suggest that the epitope specificities of the monoclonal antibodies could be determined by the conformational or topographic structure of IFN-gamma. An exact determination of the epitope specificity of the monoclonal antibody that inhibited IFN-gamma function could provide insight into the structural basis for the role of the N-terminal domain in the biologic function of IFN-gamma. Polyclonal antibodies to either the N-terminal or the C-terminal peptides also inhibited both the antiviral and the macrophage-priming activities of IFN-gamma. All of the antibodies that inhibited IFN-gamma function also blocked binding of IFN-gamma to membrane receptor on cells, whereas antibodies that did not block function also did not inhibit binding. The data suggest that both the N-terminal and the C-terminal domains of IFN-gamma play an important role in its antiviral and macrophage-priming functions, possibly in a cooperative manner.

Amino Acid Sequence↗