No abstract

No abstract

Objective To compare and quantify, in a morphological (91), 81 (20) and 74 (38) nerves/mm2 in the three defined areas, respectively. In the neuropathic tissues study, the changes that occur in the connective tissue elements (elastin and collagen), muscle fibre diameters the nerve profile densities were 672 (249), 57 (23) and 37 (28) nerves/mm2, respectively. Fibre diameter, and nerve densities between normal, idiopathic and neuropathic bladders.elastin and collagen content and nerve density were measured in normal and unstable bladder tissue using Materials and methods Bladder tissue was obtained from 27 patients undergoing cystectomy for carcithese three defined areas. The mean (sem) fibre diameter was 6.81 (0.52) in normal bladder; in idiopathic noma, from 12 with idiopathic instability and from seven neuropathic patients who were undergoing ileobladder tissue the fibre diameters in the three areas were 6.72 (0.62), 7.06 (0.62) and 7.34 (1.15) mm, cystoplasty. A combination of histochemical and immunohistochemical techniques were used to detect respectively, and in neuropathic bladders were 6.75 (0.62), 8.24 (0.62) and 9.35 (0.62) mm, respectively. detrusor muscle, connective tissue and nerve profiles in the bladder tissue.The relative areas of elastin were 0.79 (0.70), 0.56 (0.45) and 18.3 (4.1)% for the control, normal and Results In both idiopathic and neuropathic bladder tissue the structural changes were highly punctate. From aCected areas of the neuropathic bladders, respectively, and the relative areas of collagen were 3.5 (1.3), 6.15

The nucleotide sequence of the M2 gene of pneumonia virus of mice (PVM) was determined. The sequence showed that the gene encoded a protein of 176 amino acids with a predicted molecular mass of 20 165 Da from a major ORF, which is smaller than the equivalent proteins encoded by human, bovine and ovine respiratory syncytial (RS) viruses. The PVM M2 protein is conserved, having 41 % similarity to the equivalent human RS virus protein. In common with the M2 genes of the RS viruses and avian pneumovirus (APV), the PVM mRNA also contained a second ORF (ORF2) that partially overlaps the first ORF and which is capable of encoding a 98 residue polypeptide. No significant sequence identity could be detected between the putative M2 ORF2 proteins of PVM, APV and the RS viruses. The expression of the M2 ORF2 proteins of the pneumoviruses was investigated by using monospecific antisera raised against GST fusion proteins. Western blot analysis demonstrated the presence of polypeptides encoded by M2 ORF2 of PVM and RS virus corresponding with those predicted by in vitro translation studies, but this was not the case for APV. The PVM polypeptide was present as three distinct products in vivo. The PVM and RS virus polypeptides were also detected in cells by immunofluorescence, which showed that both were present in the cytoplasm with a degree of localization in inclusion bodies. No APV M2 ORF2 protein could be detected in vivo. The RS virus M2 ORF2 polypeptide was shown to accumulate during infection and the potential implications of this are discussed.

SUMMARYThe nucleotide sequence of the haemagglutinin-neuraminidase (HN) gene of Newcastle disease virus (NDV) has been determined. The HN gene is 2031 nucleotides long, approximately 13.5% of the viral genome. The nucleotide sequence contains a single long open reading frame which would encode a protein of 577 amino acids, with a mol. wt. of 63149. This is in good agreement with estimates of the molecular weight of the unglycosylated HN protein. Analysis of the amino acid sequence reveals six potential glycosylation sites and shows the major hydrophobic region to be close to the N terminus. This provides evidence for the N-terminal attachment of HN to the viral membrane. The hydrophilic nature of the extreme N-terminal amino acids suggests the absence of a cleaved signal sequence. Analysis of the long non-coding region at the 3' end of the mRNA encoded by the HN gene of NDV suggests a possible explanation for the origin of HN0 in extremely avirulent strains of NDV. There are regions of high homology between the deduced amino acid sequence of the NDV HN glycoprotein and the HN glycoproteins of two other paramyxoviruses, Sendai virus and simian virus 5 (SV5). An alignment of the HN amino acid sequences of these viruses shows 32% of amino acid residues are conserved between NDV and SV5, and 23% between NDV and Sendai virus. In contrast, only very limited homology is found between NDV HN and the influenza virus glycoproteins.

No abstract

There was a significantly higher proportion of EGFr+ tumours in the endocrine failure group compared with the control population (P<0.001).EGFr status is a marker for rapid early progression on primary endocrine therapy and the development of non-excisional methods of EGFr analysis would allow better directed therapeutic decisions.The anti-oestrogen drug tamoxifen, and the aromatase inhibitor aminoglutethimide, have been extensively tested in metastatic breast cancer with overall objective remission rates of around 30% (Cole & Todd, 1976;Ward, 1973;Murray & Pitt, 1981; Harris et al., 1986a,b). The lack of serious toxicity in the case of tamoxifen has made this a particularly attractive therapy where quality of life was as important as prolongation (Stewart et al., 1980). In advanced disease ER status predicts response to endocrine therapy (Block et al., 1975;McGuire et al., 1975;Roberts et al., 1978).The proportion of patients with ER positive primary breast cancers increases with age such that about 70% of patients over 70 years of age have ER positive tumours (Allegra et al., 1979; Elwood & Godolphin, 1980). These observations may in part account for the relatively good prognosis for some elderly patients with breast cancer.Tamoxifen had proved useful in the treatment of many elderly patients with advanced or metastatic breast cancer (Ingle et al., 1981;Legha et al., 1978). The use of pharmacological endocrine manipulation as the sole treatment of primary operable breast cancer in the elderly has been reported in several small studies (Preece et al., 1982;Hellenberg et al., 1982;Bradbeer, 1985;Allan et al., 1985;Horgan et al., 1986), and in one randomised prospective study (Gazet et al., 1988), to be an alternative to surgery. Steroid receptor status at relapse was not reported in these studies but in one (Allan et al., 1985) the response rate for ER positive tumours was found to be similar to the overall response rate.The use of primary endocrine therapy for many elderly patients with operable breast cancer became our standard practice in mid-1984. However, not all elderly patients will respond to tamoxifen and some relapse rapidly (within 6 months) without any initial control of tumour growth. We have shown previously that EGF receptor status is a strong prognostic factor in primary breast cancer (Sainsbury et al., 1987 EGFr to age, relapse in elderly patients on primary endocrine therapy, and its role in predicting tumour recurrence in elderly patients treated by primary surgery. Patients and methodsFifty-one patients over seventy years and ten in their late sixties with severe intercurrent medical illness or severe psychological aversion to mastectomy who were otherwise considered to have primary operable breast cancer were offered primary endocrine therapy. Patients with proven distant metastases at the time of presentation, as assessed by biochemical and clinical criteria, were excluded from this study.The study population comprised 61 patients. The median age was 77 years (range 64-96) and all patients ...

Epidermal growth factor receptor (EGFr) assays were performed by 3 different methods on 246 human primary breast carcinomas. Scatchard analyses of multipoint binding data on 19 of the first 209 tumours, performed by a displacement method, demonstrated that the majority of tumours exhibited 2 classes of binding site, the high-affinity site with an affinity constant (KD) of mean 2 nmol/l (SD 1.3, range 0.44-7 nmol/l), and a low-affinity site, KD mean 9.5 nmol/l (range 6-15.5 nmol/l). Scatchard analysis of multipoint assays using increasing concentrations of 125I-labelled EGF showed that saturation of the high-affinity site occurred in the majority of saturation of the high-affinity site occurred in the majority of tumours at a concentration of labelled EGF of I nM. Comparison of the KD values of the high-affinity site obtained from displacement assays with those obtained by increasing labelled EGF showed that the KD was significantly higher (p = 0.0002) when measured by the latter method. There was no difference in binding capacity of the high-affinity or low-affinity sites by the 2 methods. A 2-point assay with I nM labelled EGF (specific activity approx. 80-130 microCi/microgram) correlated with quantitative values for the high-affinity site from Scatchard analysis (p less than 0.02). There was a strong inverse relationship between EGFr greater than 10 fmol/mg membrane protein (2-point assay) and ER (dextran-coated charcoal method), Chi-squared 2 X 2 contingency table test = 34.027, p less than 0.0001. Follow-up data from 135 patients revealed a strong inverse relationship between EGFr greater than 10 fmol/mg membrane protein and oestrogen receptor (ER) status and a positive correlation with early recurrence and death. Our data describe a reproducible assay for EGFr and show that a cut-off point at 10 fmol/mg allows clinically useful application.