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Biomedical subjects

D Pearson

Publications and source records attributed to D Pearson.

At least 109 records · Page 6Linked to original sources
PubMed1990

Assessment of four monoclonal antibodies as serum markers in breast cancer.

Four monoclonal-antibody-defined serum markers (CA15-3, HMFG1, HMFG2 and NCRC-11) were examined in five groups of subjects: controls, benign breast disease and stage I/II, stage III and metastatic breast cancer. None of the markers were significantly elevated in primary breast cancer (i.e. stage I/II or stage III) compared with controls or patients with benign breast disease. These markers therefore have no role in screening or in the diagnosis of primary breast cancer. CA15-3, HMFG2 and NCRC-11 were significantly increased in the patients with metastatic breast cancer (P less than 0.001), indicating a potential use in the diagnosis of symptomatic metastases. In patients with metastases, sequential changes in CA15-3 correlated significantly with clinical response to therapy. Thus CA15-3 is a powerful marker of response and in combination with other markers, may provide an objective measurement of response to therapy in patients with advanced breast cancer.

Adult↗
PubMed1990

Behavioral symptoms in cystic fibrosis vs. neurological patients.

In this study, the authors compared the adaptation of a group of patients with cystic fibrosis (CF) (N = 46; mean age = 10.91 years) to a similar group of patients who attended a neurological clinic (N = 71; mean age = 10.47). Both groups were assessed using the Child Behavior Checklist by Achenbach (parent version). CF patients demonstrated significantly less psychosocial morbidity than the neurological patients. This was true for overall behavioral symptoms, externalizing and internalizing symptoms, and social competence. The findings indicate better adaptation by the CF group and further support the literature indicating better adaptation in CF patients over other chronically ill groups. Possible reasons for such findings are discussed.

Adolescent↗
PubMed1990

An objective biochemical assessment of therapeutic response in metastatic breast cancer: a study with external review of clinical data.

A series of tumour related markers have been examined in 179 patients receiving primary endocrine therapy for metastatic breast cancer. Significant correlations between therapeutic response (UICC criteria after 6 months of treatment) and appropriate alterations in serum concentrations of carcinoembryonic antigen, ferritin, c-reactive protein, orosomucoid and the erythrocyte sedimentation rate, have been observed when changes in these markers were examined only at high serum concentrations. By combining these five markers a 'therapeutic index' of response has been devised which can be employed at an early stage of treatment in more than 90% of patients, giving an overall sensitivity/specificity of 90%/78% for therapeutic response or disease stabilisation over a 6-month period. The design of an objective measurement of response, which is easy to perform, has the potential to replace the existing, largely subjective. UICC criteria for retrospective judgement of response, and may also be used to direct systemic endocrine therapy.

Biomarkers, Tumor↗
PubMed1990

Cytological grading of breast carcinoma--a feasible proposition?

Fine needle aspiration cytology (FNAC) of the breast is widely used in the diagnosis of breast carcinoma. In some centres this is sometimes the only diagnostic procedure performed prior to definitive treatment. A grading system based on cytology would be helpful in the selection of patients for appropriate therapy. The aim of this study, therefore, was to devise such a system for grading breast carcinoma based on cytological features alone. The features assessed were the degree of cell clustering, nuclear pleomorphism, nuclear diameter, the presence of multiple, easily visible nucleoli and necrosis. Cytological features were compared to the histological grade of the tumours following excision. Discriminant analysis showed that the features with the closest correlation with histological grade were nuclear diameter, nuclear pleomorphism and the presence of nucleoli. A scoring system based on these three parameters enabled the classification of tumours into high and low cytological grades which showed a close correlation with histological grade.

Biopsy, Needle↗
PubMed1990

Impaired muscle glycogen resynthesis after eccentric exercise.

Eight men performed 10 sets of 10 eccentric contractions of the knee extensor muscles with one leg [eccentrically exercised leg (EL)]. The weight used for this exercise was 120% of the maximal extension strength. After 30 min of rest the subjects performed two-legged cycling [concentrically exercised leg (CL)] at 74% of maximal O2 uptake for 1 h. In the 3 days after this exercise four subjects consumed diets containing 4.25 g CHO/kg body wt, and the remainder were fed 8.5 g CHO/kg. All subjects experienced severe muscle soreness and edema in the quadriceps muscles of the eccentrically exercised leg. Mean (+/- SE) resting serum creatine kinase increased from a preexercise level of 57 +/- 3 to 6,988 +/- 1,913 U/l on the 3rd day of recovery. The glycogen content (mmol/kg dry wt) in the vastus lateralis of CL muscles averaged 90, 395, and 592 mmol/kg dry wt at 0, 24, and 72 h of recovery. The EL muscle, on the other hand, averaged 168, 329, and 435 mmol/kg dry wt at these same intervals. Subjects receiving 8.5 g CHO/kg stored significantly more glycogen than those who were fed 4.3 g CHO/kg. In both groups, however, significantly less glycogen was stored in the EL than in the CL.

Adult↗
PubMed1990

Serum ferritin as a marker of therapeutic response in stage III and IV breast cancer.

Ferritin concentrations have been measured in serum from 266 patients receiving primary endocrine therapy for advanced breast cancer. Concentrations were significantly higher at presentation of advanced disease than in 55 tumour-free control patients. A positive correlation existed between increasing serum ferritin and tumour burden at presentation. A strong correlation was also found between therapeutic response and changes in serum ferritin (above 200 micrograms/l) in patients with distant metastases. More than one third of patients presenting with Stage IV disease developed concentrations in excess of 200 micrograms/l during initial treatment.

Adult↗
PubMed1989

Results of the United Kingdom Children's Cancer Study Group's malignant germ cell tumor studies.

The United Kingdom Children's Cancer Study Group's malignant germ cell tumor studies were undertaken to establish standard protocols for investigating, staging, and treating children, and to study the efficacy of new drug combinations and the value of serial measurement of serum alphafetoprotein (AFP) and human chorionic gonadotrophin (HCG). Boys with Stage I testicular tumors were treated by orchidectomy alone, whereas, after appropriate surgery, chemotherapy was recommended for children with more advanced testicular tumors or with tumors at other sites. From 1979 to 1987, 126 children aged 0 to younger than 16 years with malignant germ cell tumors were registered. They were similar to patients in other large pediatric series with respect to sites of origin, age at presentation in relationship to primary site, histology, female predominance for sacrococcygeal site, and presence of associated malformations (present in 17%). Serum AFP was measured in 123 patients and was elevated in 115, whereas HCG was raised in 19 of 77. Monitoring by serial AFP measurement proved valuable in assessing response to therapy and in early detection of tumor recurrence. When treatment results were assessed in February 1988, 101 of 122 patients were alive (four who received nonprotocol chemotherapy were excluded). Forty-four patients had been cured by surgery alone (41 with testicular tumors, two with ovarian tumors, and one with sacrococcygeal tumor). All of the remaining 78 children received chemotherapy. The initial low dose vincristine, actinomycin, and cyclophosphamide (LDVAC) regimen proved ineffective, actuarial survival at 5 years followup being 8% (12 patients), and a regimen of cisplatin, vinblastine, and bleomycin (PVB) caused unacceptable toxicity, with actuarial survival at 5 years follow-up being 67% (nine patients). Five-year actuarial survival was 87% for 17 children given high dose VAC with or without doxorubicin and 84% for 33 given bleomycin, etoposide, and cisplatin (BEP). All 7 children given various combinations of these regimens survived. Excluding the 12 LDVAC cases, patient survival by site was as follows: testis (59 patients, 100%); vagina, uterus, and prostate (four patients, 100%); ovary (25 patients, 88%); thorax (five patients, 40%), and other (four patients, 67%). Similarly, patient survival by stage was Stage I (62,97%), Stage II (14,86%); Stage III (18,83%); and Stage IV (16,72%). Survival by histology was analysed only in cases for which histologic review had been done the LDVAC cases were excluded.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1989

Diagnostic criteria for adult respiratory distress syndrome: time for reappraisal.

To assess whether current diagnostic criteria for the adult respiratory distress syndrome (ARDS) may limit research to patients with a range of severity of respiratory failure and risk factors for ARDS were studied. In 28 patients ARDS did not develop; in 9 it did; and the other 13 met the diagnostic criteria at their first assessment. Plasma concentration of neutrophil elastase-alpha 1-antitrypsin complex was higher in all groups than in controls. For all patients, plasma elastase-complex was related to worsening hypoxia and to increased bronchoalveolar lavage protein content. Elastase-complex was present in all bronchoalveolar lavage samples and was related to protein content and differential neutrophil counts. Patients at risk of or with ARDS had a spectrum of respiratory failure to which intravascular and intra-alveolar neutrophil elastase release and capillary permeability were related. This suggests that the state recognised as ARDS is not a distinct pathophysiological entity.

Adult↗
PubMed1989

Heterogeneity of enzyme-altered foci in rat liver.

Enzyme-altered foci (EAF) in liver are assumed to be precursor lesions for tumors in this organ. Results obtained with selected hepatocarcinogens which produce lesions of differing phenotype and growth behavior indicate that not the total number of enzyme-altered cells but rather the proliferation of individual cell clones is of major importance for additional changes leading to malignancy. Analyses including multiple marker enzymes demonstrate a relationship between foci phenotype and proliferation. The inducibility of certain downregulated enzymes in EAF indirectly suggests disturbances in the expression of regulatory genes such as proto-oncogenes. Data on Ha-ras and c-myc proto-oncogene expression in EAF are presented.

Adenosine Triphosphatases↗
PubMed1989

The radiographic differentiation of pulmonary oedema.

A radiographic scoring system has been reported to have a high diagnostic accuracy in the differentiation of pulmonary oedema of renal, cardiac and capillary origin. In the present study, a similar scoring system was used in 51 patients with radiographic appearances of pulmonary oedema due to renal failure (n = 16), cardiac failure (n = 13) and to adult respiratory distress syndrome (ARDS) (n = 22). Evidence of increased pulmonary capillary permeability to transferrin was sought in all patients using a double-isotope method to derive a protein accumulation index (PAI). Using the clinical diagnosis of each type of pulmonary oedema as the "gold standard", sensitivity, specificity and accuracy for the chest radiographic scoring system in pulmonary oedema of cardiac origin were 46, 84 and 75%, respectively. For renal patients these values were 63, 86 and 78% and for ARDS, 89, 33 and 77%. For the PAI in ARDS, sensitivity was 85%, specificity 67% and accuracy 86%. The radiographic scoring system failed to distinguish between pulmonary oedema of renal and cardiac origin and cannot be considered of diagnostic value, but it was more successful in assessment of ARDS. Radiographic appearances suggestive of capillary injury and increased capillary permeability to transferrin occurred in all groups and such findings are not specific to ARDS as currently defined.

Acute Kidney Injury↗
PubMed1988

Multiple nuclear factors interact with promoter sequences of the urokinase-type plasminogen activator gene.

To characterize proteins that bind to the cyclic AMP inducible promoter of the urokinase-type plasminogen activator gene, we performed a DNAase I footprinting analysis. Within 500 nucleotides upstream of the transcription start site we found eight protected regions due to at least four different binding proteins. Among these is a single binding site for the transcription factor CTF/NF1, which is flanked on each side by two conserved binding sites for the transcription factor Sp1. A region at -380, which shares a similarity with sequences observed in the corresponding regions of other cyclic AMP regulated genes, was protected. This binding site contains a sequence of ten nucleotides which is repeated further upstream at -480 and also protected against DNAase I digestion. Comparisons of extracts from four different cell lines revealed that all DNA binding factors are present in nuclei of uPA expressing and nonexpressing cells. Mechanism underlying hormonal regulation of the gene is discussed.

Animals↗
PubMed1988

Improvements in survival from childhood cancer: results of a population based survey over 30 years.

Survival from cancer of children whose cancer was diagnosed during the 30 years 1954-83 was analysed. The study was population based with nearly 3000 cases covering about 30 million child years at risk. When survival during the three decades 1954-63, 1964-73, and 1974-83 was compared striking improvements were observed. For all childhood cancer five year survival increased from 21% in the first decade to 49% in the third decade. During the first and third decades five year survival rates for acute lymphocytic leukaemia increased from 2% to 47%, Hodgkin's disease from 44% to 91%, non-Hodgkin's lymphoma from 18% to 45%, Wilms's tumour from 31% to 85%, and germ cell tumours from 10% to 64%. Twenty patients developed second primary tumours, but otherwise there were few late deaths. Less than 1% of children who survived without a relapse for 10 years subsequently died of their initial cancer. Survival from childhood cancer is no longer rare, and people who have been cured of cancer during childhood should be accepted as normal members of society.

Adolescent↗
PubMed1988

hsp70 mRNA accumulates in LLC-PK1 pig kidney cells treated with calcitonin but not with 8-bromo-cyclic AMP.

In LLC-PK1 pig kidney cells, treatment with a cAMP-elevating peptide hormone, calcitonin, induces the accumulation of urokinase-type plasminogen activator (uPA) mRNA. When we used the method of differential hybridization to isolate uPA cDNA clones, we also obtained several calcitonin-inducible clones that were unrelated to uPA. Sequence analysis revealed 60% sequence homology between one of these clones and that of a Drosophila hsp70 gene. The uPA and the hsp70 cDNA clones were used as probes to compare the effects of various treatments on the accumulation of uPA mRNA and hsp70 mRNA in LLC-PK1 cells. Calcitonin or 8-bromo-cAMP treatment induced uPA mRNA accumulation, which was negligible in untreated cells. Heat treatment (42 degrees C) was ineffective. Calcitonin or heat treatment increased hsp70 mRNA accumulation, which was already high in untreated cells, but 8-bromo-cAMP was ineffective. Nuclear transcription of the hsp70 gene was increased by calcitonin but not by 8-bromo-cAMP treatment. These results suggest that calcitonin induces hsp70 mRNA accumulation in LLC-PK1 cells by a pathway apart from the activation of adenylate cyclase and through, at least partly, the activation of the gene transcription. Furthermore, induction of uPA mRNA accumulation by calcitonin or 8-bromo-cAMP treatment did not require protein synthesis. In contrast, induction of hsp70 mRNA accumulation by calcitonin or heat treatment did require protein synthesis. Other reports showed that protein synthesis is not required for heat induction of hsp70 mRNA in different cells, suggesting that the mechanism of induction of hsp70 mRNA accumulation in LLC-PK1 cells is not the same as in other cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1988

Transcriptional regulation of a plasminogen activator gene by cyclic AMP in a homologous cell-free system. Involvement of cyclic AMP-dependent protein kinase in transcriptional control.

We have developed a homologous cell-free transcription system using extracts from the porcine kidney cell line LLC-PK1 to study the molecular mechanisms by which cAMP regulates urokinase-type plasminogen activator (uPA) gene transcription. We demonstrated accurate initiation of transcription using a cloned fragment of the uPA gene as template. The in vitro transcription rate was stimulated by up to 10-fold by the addition of cAMP (greater than 10 microM). This effect of cAMP on the transcription was greater for closed circular than for linear templates. Furthermore, addition of the purified catalytic subunit of cAMP-dependent protein kinase stimulated the in vitro transcription in the absence of cAMP to levels 2-fold higher than those observed with cAMP. Addition of cAMP had no stimulatory effect on the transcription of the rat heme oxygenase gene promoter tested under identical conditions. HeLa whole cell extract by itself showed no stimulation of transcription of the uPA gene by cAMP. Results of reconstitution experiments using HeLa whole cell extracts and nuclear lysates from LLC-PK1 cells suggest the presence of putative cAMP regulatory factor(s) as well as general transcription factor(s) in the nucleus of LLC-PK1 cells. These results provide experimental evidence directly implicating cAMP-dependent protein kinase in the regulation of gene transcription.

Animals↗
PubMed1988

Neutrophil degranulation and increased pulmonary capillary permeability following oesophagectomy: a model of early lung injury in man.

In nine subjects undergoing oesophagectomy a transient but significant increase in pulmonary vascular permeability to transferrin was detected in both lungs 8 h after surgery. It coincided with a significant increase in plasma lactoferrin, evidence of intravascular and intra-alveolar neutrophil elastase release and with arterial hypoxaemia. The postoperative state in these patients had intravascular and pulmonary features often associated with the adult respiratory distress syndrome, and might be a useful model for the study of the early inflammatory events underlying lung injury in man.

Aged↗
PubMed1988

Tenascin: cDNA cloning and induction by TGF-beta.

cDNA clones coding for tenascin, an extracellular matrix glycoprotein with a restricted tissue distribution, were isolated from a chicken fibroblast cDNA expression library using a specific tenascin antiserum. Antibodies eluted from the cDNA-encoded fusion proteins reacted exclusively with tenascin. Limited trypsin treatment of purified tenascin resulted in a peptide which confirmed the deduced protein sequences. The largest clone encoding 632 amino acids showed a cysteine-rich region containing 13 consecutive epidermal growth factor-like repeats of unusual uniformity. Northern blot analysis revealed 8- to 9-kb messages. Tenascin is shown to be induced in vitro by fetal calf serum as well as by transforming growth factor beta (TGF-beta). A 4-fold increase in tenascin secretion by chick embryo fibroblasts was seen after TGF-beta treatment. The induction of tenascin protein synthesis was preceded by an increase of tenascin mRNA as determined by Northern blot analysis. The induction of tenascin was compared with fibronectin. The accumulation of the two extracellular matrix proteins in the medium was differentially affected by fetal calf serum and TGF-beta and the increase was in both cases higher for tenascin.

Amino Acid Sequence↗
PubMed1988

Reinnervation of sweat glands in the rat hind paw following peripheral nerve injury.

Electrophysiological experiments have been carried out to investigate the time course and extent of sweat gland reinnervation in the rat hind paw. The first evidence of functional reinnervation after nerve transection was obtained at 12 weeks, when the extent of innervation was 20% of that measured in control animals. By 20 weeks, reinnervation had reached almost 50% of control values but then there was no further improvement up to 52 weeks. These results are comparable to those for skin reinnervation by polymodal nociceptor afferents.

Animals↗