Search PubMed⌕ Search

Biomedical subjects

A Herbert

Publications and source records attributed to A Herbert.

At least 91 records · Page 5Linked to original sources
PubMed1992

Zuotin, a putative Z-DNA binding protein in Saccharomyces cerevisiae.

A putative Z-DNA binding protein, named zuotin, was purified from a yeast nuclear extract by means of a Z-DNA binding assay using [32P]poly(dG-m5dC) and [32P]oligo(dG-Br5dC)22 in the presence of B-DNA competitor. Poly(dG-Br5dC) in the Z-form competed well for the binding of a zuotin containing fraction, but salmon sperm DNA, poly(dG-dC) and poly(dA-dT) were not effective. Negatively supercoiled plasmid pUC19 did not compete, whereas an otherwise identical plasmid pUC19(CG), which contained a (dG-dC)7 segment in the Z-form was an excellent competitor. A Southwestern blot using [32P]poly(dG-m5dC) as a probe in the presence of MgCl2 identified a protein having a molecular weight of 51 kDa. The 51 kDa zuotin was partially sequenced at the N-terminal and the gene, ZUO1, was cloned, sequenced and expressed in Escherichia coli; the expressed zuotin showed similar Z-DNA binding activity, but with lower affinity than zuotin that had been partially purified from yeast. Zuotin was deduced to have a number of potential phosphorylation sites including two CDC28 (homologous to the human and Schizosaccharomyces pombe cdc2) phosphorylation sites. The hexapeptide motif KYHPDK was found in zuotin as well as in several yeast proteins, DnaJ of E.coli, csp29 and csp32 proteins of Drosophila and the small t and large T antigens of the polyoma virus. A 60 amino acid segment of zuotin has similarity to several histone H1 sequences. Disruption of ZUO1 in yeast resulted in a slow growth phenotype.

Amino Acid Sequence↗
PubMed1992

A new anthelmintic assay using rats infected with Trichostrongylus colubriformis.

A new anthelmintic assay is described which uses immunosuppressed (60 ppm hydrocortisone acetate in diet) rats infected with the nematode Trichostrongylus colubriformis. Immunosuppressed rats were infected with 1500 T. colubriformis larvae, treated either orally or subcutaneously on Day 14 post-infection and necropsied 4 days after treatment. The worm counts in immunosuppressed control animals averaged 775 worms per rat. A range of benzimidazoles, levamisole hydrochloride, morantel tartrate, 22,23-dihydroavermectin B1a and alpha-milbemycin have been evaluated in the assay. The ED95 values obtained indicate that rats infected with T. colubriformis provide a highly predictive model for assaying the activity of experimental drugs in vivo prior to studies in ruminants.

Animals↗
PubMed1992

Assessment of the accuracy of cytology in women referred for colposcopy and biopsy: the results of a 1 year audit.

The results of weekly colposcopy review meetings have been audited for 1 year and cases where there was a discrepancy between the referral cervical smear and the initial colposcopy biopsy have been analysed. New referrals (n = 476) for colposcopy were studied. In the final outcome 80% of 326 women referred for moderate or severe dyskaryosis were found to have cervical intraepithelial neoplasia (CIN) grade II or III or invasive carcinoma. Three women found to have invasive carcinoma had been referred for severely dyskaryotic smears. Twenty women were referred for smears with cell changes suggesting glandular neoplasia: five were found to have adenocarcinoma in situ, whereas eight had CIN and seven had negative biopsies. The results justify the referral policy and demonstrate the need for further investigation when initial colposcopic biopsies are negative.

Adenocarcinoma↗
PubMed1992

Reduction of alveolar-capillary diffusion after inhalation of endotoxin in normal subjects.

Normal subjects were exposed to an aerosol of Escherichia coli endotoxin. Carbon monoxide diffusion (Dco), spirometry, blood neutrophils, white blood cells, and platelets were determined at various times thereafter. A significant decrease in Dco and an increase in blood neutrophils was found, with a maximum effect 4 to 8 h after exposure. Exposure to distilled water caused a tendency for Dco to decrease and a significant increase in blood neutrophils. No effect on spirometry or body temperature was detected. It is suggested that the changes observed represent an inflammation at the alveolar level that appears at dose levels of endotoxin below those which cause bronchoconstriction and fever.

Administration, Inhalation↗
PubMed1992

The relationship between clinical staging, oestrogen receptor status and silver-binding nucleolar organiser regions (AgNOR) in breast carcinoma.

Forty benign and 31 malignant breast tissues were examined using a one stage colloid-stabilising silver technique for argyrophilic nucleolar organiser regions (AgNOR). In 31 patients TNM staging was correlated to AgNOR score. There was a positive correlation with the T-stage and AgNOR score of the tumor (Spearman's rank correlation coefficient = 0.437). The N-stage and AgNOR score for breast cancers (n = 10) were inversely related, and there was a significant difference between the lymph node positive and negative groups (P less than 0.05). No significant relationship was identified between oestrogen receptor negative and positive groups and AgNOR score (P = 0.63). Mean regression analysis suggests that independent of the Bloom's grade, the AgNOR score is an indicator of tumour size.

Breast Diseases↗
PubMed1991

Erythropoietic protoporphyria: unusual skin and neurological problems after liver transplantation.

The case of a woman with protoporphyria who developed liver failure and underwent liver transplantation is described. During the pretransplant episode of liver failure she developed quadriparesis that rapidly progressed after transplantation to a severe polyneuropathy. Following transplantation she also developed a second-degree burn of the light-exposed abdominal wall. The neuropathy resembled that observed in other forms of porphyria, and it is proposed that the extreme disturbance of protoporphyrin levels associated with protoporphyrin-induced liver failure caused this neuropathy. Such a neuropathy has not previously been described in protoporphyria. Erythrocyte protoporphyrin levels remain high and fecal levels normal, although results of liver tests are normal. She remains photosensitive, which emphasizes that although liver transplantation may be lifesaving in this disorder, it is not curative, and care must be taken to prevent photosensitive damage to skin and light-exposed internal organs.

Adult↗
PubMed1991

A novel process for preparing an acellular pertussis vaccine composed of non-pyrogenic toxoids of pertussis toxin and filamentous hemagglutinin.

A novel process for preparing non-pyrogenic toxoids of pertussis toxin (PT) and filamentous hemagglutinin (FHA) is described. The process consists of chromatographies on perlite then on hydroxylapatite. Purification yields for PT and FHA are 62 and 68%, respectively. The purification process takes advantage of the novel use of perlite (a filter aid) for the simultaneous purification of PT and FHA. The hydroxylapatite, in addition to removing the remaining contaminants, also concentrates the antigens. The resulting PT and FHA are approximately 95% pure, and are non-pyrogenic as judged by the rabbit pyrogen test. The purification process is simple, inexpensive, and does not use blood components or toxic substances. The mild conditions in which the PT and FHA are purified ensure the recovery of native protein. The purified PT and FHA are detoxified in the presence of glycerol using glutaraldehyde and formaldehyde, respectively, to produce antigenic components of an acellular pertussis vaccine. The final PT and FHA toxoids are immunogenic in guinea-pigs and have been shown to be protective in the mouse intracerebral challenge test.

Bordetella pertussis↗
PubMed1991

del(15)(q11q15) associated with transformation of chronic myelomonocytic leukemia.

Nonrandom cytogenetic abnormalities have been described in a variety of human malignancies including myelodysplastic syndromes (MDS). Acquisition of new chromosomal abnormalities may herald onset of a more aggressive disease. We report a patient with chronic myelomonocytic leukemia (CMMoL) who initially had a normal karyotype, but in whom the clonal interstitial deletion of chromosome 15 (q11-q15) was coincident with development of acute myeloid leukemia (AML) one year later. To date, this chromosomal change has not been reported in CMMoL, AML, or any other human malignancy.

Aged↗
PubMed1991

Impact of an extensive in situ component on the presence of residual disease in screen detected breast cancer.

This study investigates the histopathological characteristics of a consecutive series of 100 screen detected breast cancers in relation to residual disease. Tumour type, size, grade, resection margins and extent of primary or associated in situ disease were all assessed by one pathologist. Thirty-seven women underwent further surgery (wider excision or mastectomy) and the resected specimen was examined for residual in situ or invasive cancer. In total, 36 cancers had an extensive in situ component, of which 69% were predominantly intraduct carcinoma of comedo type. Of the 37 women who underwent further resection, 21 (57%) women had residual cancer. Of those with initial disease at the resection margin, 16/25 (64%) had residual disease. Five of 12 (42%) with disease close to (within 2-3 mm) but not at the margin had residual disease. Of those with an extensive in situ component, 18/25 (72%) had residual disease, whereas only 2/12 (17%) women with none or some in situ disease had residual cancer. In screen detected breast cancer, residual cancer was present in 72% of women with an extensive in situ component at initial surgery. These women comprise a group in which conservation surgery may be inappropriate if completeness of excision is considered a prerequisite for breast conserving surgery.

Breast Neoplasms↗
PubMed1991

ERICA predicts response to tamoxifen in elderly women with breast cancer.

Oestrogen receptor status has been determined by an immunocytochemical assay using fine-needle aspiration samples of primary breast cancers in elderly patients. In a prospective study 56 patients were treated with tamoxifen only. Satisfactory assays were achieved in 49 patients. Disease was controlled by tamoxifen in 32 of 35 (91%) patients with oestrogen receptor positive tumours, compared with only 1 (7%) of 14 who were receptor negative. Immunocytochemical assay on fine-needle aspiration samples is relatively non-invasive and simple to perform, it accurately predicts response to tamoxifen in elderly patients and can be used to select patients for tamoxifen only therapy.

Aged↗
PubMed1990

Synthesis and characterization of soluble dextran-adenosine phosphate complexes: kinetic effects of coenzyme loading.

Soluble dextran-ATP complexes have been synthesized using a bifunctional oxirane as the coupling agent. The degree of coupling is time-dependent, allowing materials of varying coenzyme loadings to be produced very simply. Characterization studies have shown that at the maximum coenzyme loading obtained (34 molecules per complex) all coenzyme moieties were coenzymically active with hexokinase. The extent of coenzyme loading was shown to have a considerable influence on the values of Km and Vmax of the complex as a substrate for hexokinase. Enzyme activity was also found with acetate kinase and myokinase, and coenzyme recycling (ATP, ADP) was demonstrated in an ultrafiltration reactor.

Acetate Kinase↗
PubMed1990

Cytology of colorectal adenomas.

A study of the cytological appearances of benign and malignant colorectal adenomatous polyps is reported. The aim of the study was to characterize the cytological features of adenomatous polyps and predict the likelihood of malignancy using cytology. A five grade classification of colorectal cytology has been developed and the characteristic appearances of cells from adenomatous polyps are described. The reproducibility of cytological diagnosis based on this classification has been tested in 120 smears from normal mucosa and adenomatous polyps (including polyp cancers). Correlation with histology was achieved in 88% and correlation of the cytological diagnosis between two observers was achieved in 84%. We conclude that cytology can be used reliably as an adjunct to histology in the assessment of malignancy of adenomatous polyps.

Adenoma↗
PubMed1990

Demonstration of oestrogen receptor in symptomatic breast carcinoma, using fine needle aspiration cytology.

Oestrogen receptor immunocytochemical assay (ER-ICA) was used to determine oestrogen receptor (ER) content of cells in fine needle aspirate (FNA) specimens from 88 breast carcinomas. In 49 of these the radioligand binding assay for oestradiol was available for comparison. The predictive value of ER-ICA staining for a positive radioligand binding assay (greater than 10 fmol/mg protein) was 95%. Although the predictive value of negative staining was only 66%, 34 out of 37 ER-ICA negative tumours had radioligand binding assays below 60 fmol/mg protein. ER-ICA staining showed a strong positive correlation with age of the patient, positivity being rare before the menopause. There was a weak inverse correlation with tumour grade but none with tumour size or lymph node status. The assessment of ER by immunocytochemistry using FNA cytology is a rapid technique, which may easily be repeated and provides a pre-operative assessment of ER status. It allows confirmation that tumour cells are present in the sample and an assessment of tumour heterogeneity.

Adult↗
PubMed1989

Clinical, radiological and cytological diagnosis of breast cancer in young women.

In women over the age of 35 years, an accurate diagnosis of breast cancer can be made in over 95 per cent of patients using a 'triple assessment' system collating information from clinical examination, mammography, sonomammography, and fine-needle aspiration cytology. These methods have not been specifically evaluated in women aged 35 years or less, hence a study was undertaken on 30 such patients. Clinical examination was unreliable in predicting malignancy with a sensitivity of only 37 per cent. Thirty per cent of patients presented with a lump which had the clinical features of a fibroadenoma. Radiological methods were less sensitive in detecting malignancy in this age group than in older patients. The sensitivity of aspiration cytology was 78 per cent which was higher than that for breast cancer at all ages. Histology showed that there were fewer low grade tumours and fewer scirrhous tumours in this age group than in a control group of women aged over 35 years. This study indicates that cytological confirmation of apparently benign focal breast lesions in young women is essential, especially when these are managed conservatively.

Adult↗