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Biomedical subjects

J Bishop

Publications and source records attributed to J Bishop.

At least 127 records · Page 7Linked to original sources

Automated quantification of rat plasma acute phase reactants in experimental inflammation.

Methods are described for the quantification of certain acute phase reactants (albumin, iron, fibrinogen, seromucoid, haptoglobin, and ceruloplasmin) in small amounts of plasma using the COBAS-BIO centrifugal analyzer. These methods have been applied to determine the concentrations of these acute-phase reactants (APRs) in rat plasma during the first 5 days of adjuvant-induced arthritis. The levels of the APRs alter with the degree of inflammation in a dose-related manner. Administration of the antiinflammatory and antirheumatic drugs (indomethacin, dexamethasone, and clobuzarit [CLOZIC]) during the course of the adjuvant-induced arthritis reduced the inflammatory response as judged by the measurement of oedema. These compounds, however, show differential effects on the profile of APRs as systemic measurements of the inflammatory disease. The present study shows that specific classes of drug have defined effects on acute-phase protein concentration. We believe that the multiple analysis of APR levels during the course of inflammation may help to distinguish between and elucidate the mechanisms of action, of antiinflammatory and antirheumatic drugs.

Acute-Phase Proteins↗

Dose intensity and outcome with combination chemotherapy for germ cell carcinoma. Australasian Germ Cell Trial Group.

Two hundred and fifty-three patients with advanced stage germ cell carcinoma received induction chemotherapy with vinblastine, bleomycin and cisplatin, sometimes with subsequent surgical resection of residual masses. Overall, 191 patients (76%) achieved complete remission or no evidence of disease after surgery (CR + NED). With 64 months median follow-up only 24 patients have relapsed (13%) and 68% of all patients treated are long-term survivors and 84% of patients entering CR + NED are alive. Toxicity with this chemotherapy was considerable, including seven deaths from leukopenia and septicaemia and eight deaths from bleomycin lung toxicity. Dose reductions or omissions of the drug from the treatment programme was necessary with cisplatin in 8% of patients, with vinblastine in 37% and with bleomycin in 35% of patients. Analysis of these alterations in dose intensity for each drug revealed that initial treatment response and subsequent survival were not compromised by reductions in intended doses of drug administered for either vinblastine or bleomycin. Too few patients had dose reductions of cisplatin for meaningful analysis. This apparent lack of major dose-response effect for either vinblastine or bleomycin in the present treatment programme for germ cell carcinoma has prompted the initiation of a randomized study to determine whether deletion of bleomycin from treatment for patients with good prognostic pretreatment characteristics improves the therapeutic index of this very successful therapy.

Antineoplastic Combined Chemotherapy Protocols↗

A randomized trial of cisplatin versus cisplatin plus methotrexate in advanced cancer of the urothelial tract.

One hundred eight patients with recurrent or metastatic transitional cell carcinoma of the urothelial tract were randomized to receive cisplatin (C) 80 mg/m2 on day 1 every 4 weeks, or methotrexate (M) 50 mg/m2 on days 1 and 15 plus C 80 mg/m2 on day 2 every 4 weeks (C + M). Fifty-three eligible patients were randomized to C + M and 55 to C. In the C + M arm, 45% of patients responded (complete response [CR], 9%) and 31% (CR, 9%) in the C arm (P = .18). In the C arm, 20 patients failing or relapsing after C received M. Two patients responded, and four with progressive disease (PD) and one with a previous partial response (PR) showed no change. The median survival was 8.7 months (C + M arm) and 7.2 months (C arm), P = .7. Relapse-free survival was not significantly different, but C + M was associated with a significantly increased time to disease progression (median, 5.0 months, v 2.8 months for C arm). The response of untreated patients (37%) was not different from those with prior treatment (39%). On the C + M arm, 92% of patients and 96% of patients on the C arm received 85% or more of the scheduled C dose. Significantly more grade 3 or 4 hematological toxicity (27% v 2%; P = .01) and mucositis (20% v 0%; P = .0005) occurred in patients on the C + M arm. Although the initial response rates seen on the combination arm look superior, and the time to disease progression is increased, these effects have not translated into a clinically important increase in the duration of survival and were associated with increased toxicity.

Adult↗

Detection of mammary serum antigen in sera from breast cancer patients using monoclonal antibody 3E1.2.

Murine monoclonal antibody 3E1.2, made against human breast cancer cells, detects a glycoprotein (Mr greater than 300,000) called mammary serum antigen (MSA) which is elevated in the serum of patients with breast cancer. An enzyme immunoassay was developed to detect MSA in human serum and used to detect MSA in subjects with breast cancer and other diseases. Raised levels of MSA (greater than 300 inhibition units) were found in the serum of 1.9% of 2406 blood donors, in 18% of sera from 40 subjects with benign breast disease, and in 16% of sera from 222 subjects with non-breast cancers. However, in patients with a diagnosis of breast cancer, 76% (84 of 110) of Stage I and II, and 86% (142 of 166) of Stage III and IV had levels of greater than 300 inhibition units. Nineteen % of patients, classified clinically disease free, had raised MSA levels. In 34 of 37 (92%) patients followed over 2 to 11 mo the level of MSA correlated with the clinical course of disease. Changes in MSA levels not only corresponded to changes in the clinical course of disease, but also preceded the clinical detection of progressive disease. Immunoblotting has detected a heterogeneous molecule of Mr greater than 300,000 and been used to confirm the elevation of MSA in breast cancer patients. Determination of MSA level may be useful for the detection of breast cancer and for monitoring progress of disease and response to therapy.

Antibodies, Monoclonal↗

Magnetic resonance images of chronic patellar tendinitis.

Chronic patellar tendinitis can be a frustrating diagnostic and therapeutic problem. This report evaluates seven tendons in five patients with chronic patellar tendinitis. The etiologies included "jumper's knee" and Osgood-Schlatter disease. In all cases magnetic resonance images (MRI) showed thickening of the tendon. Some of the tendons had focal areas of thickening which helped establish the etiology. All cases had intratendinous areas of increased signal which, in four cases, proved to be chronic tendon tears. MRI is useful in evaluating chronic patellar tendinitis because it establishes the diagnosis, detects associated chronic tears, and may help determine appropriate rehabilitation.

Athletic Injuries↗

Evaluation of directed coughing in cystic fibrosis.

Supervised directed coughing was compared to conventional physiotherapy (postural drainage, vibration and/or percussion and coughing) in 38 patients with cystic fibrosis aged 9-18 years admitted to hospital with an exacerbation of their pulmonary symptoms. Assessment included objective measures of pulmonary function and sputum characteristics. Both treatment groups showed significant improvement at the end of the 2-week period. When the patients were graded according to their pulmonary disease, those with mild-moderate disease demonstrated a significant improvement in both treatment groups whereas those with severe lung disease showed little improvement with either treatment. Directed coughing is as effective as conventional physiotherapy in the management of patients with cystic fibrosis admitted to hospital for treatment of an exacerbation of their pulmonary symptoms.

Adolescent↗

Transient platelet and HLA antibody formation in multitransfused patients with malignancy.

Fifty-nine patients receiving platelet transfusions for bone marrow failure secondary to malignancy were screened at regular intervals for the presence of antibodies to human leucocyte (HLA) and platelet specific antigens. HLA antibodies occurred in 19 patients, 10 of whom also developed platelet specific antibodies. The HLA antibodies disappeared in 10 of 15 patients followed for periods of 2-14 months. In two patients this occurred whilst still receiving platelet transfusions. Antibody reappeared in only two of six patients subsequently transfused. Antibodies to platelet specific antigens were detected in 28 patients. They were transient, often appeared in association with infection, and in 50% of cases tested demonstrated autoantibody activity. There was no association with antibiotic drug therapy, or PFA/EDTA-dependent cryptantigens. Platelet recovery at 1 h or 20 h post transfusion was not significantly reduced in the presence of platelet specific antibodies. These findings have important implications for the selection of platelet donors for alloimmunized recipients.

Antibodies↗

Heterogeneous cytogenetic abnormalities in small cell lung cancer cell lines.

Ten cell lines were established from different biopsies from nine patients with small cell lung cancer (SCLC). These were established from metastases in the marrow (7), breast (1), pleural fluid (1), and spinal cord (1) and had been in culture for periods varying from 1 to 11 months. All cell lines exhibited typical cytological features of SCLC, and produced neuron specific enolase. All lines examined (5) contained dense core granules and were tumorigenic when injected intracranially into nude mice. None of the six cell lines tested had an amplified oncogene (c-myc or n-myc) previously reported to be amplified in SCLC. Detailed chromosome analyses were undertaken and showed that a structural abnormality of chromosome 3(p11p23) was a frequent (6 of 10) but not invariable finding. Our study and one other indicate that there is not a unique chromosome abnormality present in all cases of SCLC, although loss of chromosome 13 and structural abnormalities of chromosome 3 were frequently found. A feature of these SCLC cell lines established from metastatic deposits was the complexity of the karyotypes due to numerical and structural chromosomal abnormalities.

Biopsy↗

Phase I study of epirubicin given on a weekly schedule.

Epirubicin was studied in a phase I setting to find the maximum tolerated dose when given weekly for 3 of 4 weeks. Forty-one evaluable patients were treated in groups at doses increasing from 20 to 45 mg/m2. The highest dose level produced the maximum degree of myelosuppression (lowest neutrophil count, 1.9 X 10(9)/L; range, 0-3.7) recorded on Day 22. This was well-tolerated in this group of mainly pretreated patients. Nonhematologic side effects were minimal. This dose schedule allows a greater dose per unit time to be administered than other recommended schedules for epirubicin.

Adult↗

Phase I and pharmacokinetic study of tiazofurin (NSC 286193) administered by 5-day continuous infusion.

A phase I and pharmacokinetic study of tiazofurin (NSC 286193), a C-nucleoside that inhibits IMP dehydrogenase, has been completed. The drug was administered by continuous infusion over 5 days. The maximum tolerated dose was 1650 mg/m2 per day, neurological toxicity being the dose-limiting factor. Gastrointestinal and hematological toxicity were mild. A definite relationship exists between dosage and steady-state levels. The plasma clearance was 29.13 (+/- SD 4.05) ml/min per m2. No complete or partial remissions were demonstrated among the 18 patients treated at five dose levels between 550 mg/m2 and 2200 mg/m2 per day.

Adult↗

Chemotherapy in metastatic melanoma: phase II studies of amsacrine, mitoxantrone and bisantrene.

In a phase II study 20 patients with measurable metastatic melanoma were treated with amsacrine 120 mg/m2 every 3 weeks. No objective responses were observed. In a separate study 29 patients received mitoxantrone 12-14 mg/m2 every 3-4 weeks. One objective partial response was seen. The drug was well tolerated. Seventeen patients were treated with bisantrene 135-200 mg/m2 weekly. No objective responses were observed. Phlebitis was the major non-hematologic toxicity of bisantrene. These agents are not recommended for treatment of malignant melanoma.

Aminoacridines↗

Structure of mouse major urinary protein genes: different splicing configurations in the 3'-non-coding region.

The multigene family which codes for the mouse major urinary proteins (MUPs) consists of approximately 35 genes. Most of these are members of two different groups, Group 1 and Group 2, which can be distinguished by nucleic acid hybridisation. Here we describe the structure of a Group 1 gene and show that two size classes of MUP mRNA which are found in mouse liver result from different splicing events in the 3'-non-coding region and contain different polyadenylation sites. Short mRNA is approximately 750 nucleotides long, contains six exons, and is the main product of the Group 2 genes. Long mRNA is approximately 880 nucleotides long, contains seven exons and is the main product of the Group 1 genes. Five exons and part of the sixth are common to long and short mRNA and contain the coding region. This codes for an acidic protein of 180 amino acids containing an 18 residue signal peptide. A comparison of the mouse sequence with a homologous rat alpha 2u-globulin sequence shows that the rate of evolutionary divergence of the two proteins has been high. Silent sites have diverged four times more rapidly than replacement sites, showing that there has been selection against change in the protein sequence.

Amino Acid Sequence↗