Search PubMed⌕ Search

Biomedical subjects

L Robertson

Publications and source records attributed to L Robertson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Expression of the BCL-2 protein in normal and dysplastic bronchial epithelium and in lung carcinomas.

Although expression of the bcl-2 protein has been investigated in a number of non-haematological malignancies, little is known of its distribution in premalignant lesions. Expression of bcl-2 was investigated immunohistochemically in archival biopsies of normal (n = 8) and dysplastic bronchial epithelium (n = 56) and in 31 bronchial resection margins and their corresponding carcinomas. All dysplasias had lost the prominent basal staining pattern seen in histologically normal epithelium. Two were negative and six had occasional basal positive cells. In 37 cases up to 66% of the epithelial cells throughout the full epithelial thickness were bcl-2 positive with weak to moderate staining intensity. In 11 cases, all severe dysplasias, strong expression was observed in > 90% of the epithelial cells. Four patterns of bcl-2 expression in dysplasias were identified and an increasingly aberrant pattern of bcl-2 expression correlated with an increasing grade of dysplasia (Spearman's rank correlation, P < or = 0.0001). Sixty-five per cent of the carcinomas contained bcl-2-positive cells. Patients with non-small-cell lung carcinomas (n = 27) in which > 50% of the tumour cells were bcl-2 positive showed a survival advantage compared with those with 0-25% bcl-2-positive cells (P = 0.02). No correlation was found between p53 expression (Walker et al., 1994) and bcl-2 expression in dysplasias or carcinomas.

Bronchi↗
PubMed1995

Value added tacks.

Explore the source record for details and available documents.

Efficiency, Organizational↗
PubMed1994

Technical aspects of transvaginal ultrasound-guided follicular aspiration in cows.

A 7.5 MHz rectal transducer adapted for transvaginal use was compared with a human microcurvilinear 6 MHz transvaginal transducer for follicular aspiration in cows. Some of the problems encountered while developing an accurate and repeatable technique are discussed, including the preparation of the cow, and the selection of the needle and suction apparatus. Proficiency in the retrieval of oocytes was improved through practice. Four cows were aspirated on days 2 to 4, 9 to 12 and 15 to 16 after oestrus in two successive oestrous cycles. The initial recovery rates were poor (7 per cent) and the oocytes were of poor quality, being almost completely denuded. However, after five weeks' practice recovery rates of 41 per cent were achieved and the oocytes were suitable for in vitro maturation.

Animals↗
PubMed1994

Serum p53 auto-antibodies: incidence in familial breast cancer.

Inactivation of the p53 gene, which codes for a tumour suppressor protein, is known to occur in the majority of human malignancies. An ELISA technique has been developed which has detected auto-antibodies to p53 in the serum of 25.6% of 176 women with breast cancer, considerably higher than previously reported with an immunoblotting technique. The incidence of auto-antibodies in those cases with a family history of breast cancer was 9.1%, compared to 29.4% in those with no family history (P = 0.029). In women without clinical breast cancer, 4 out of 36 (11.1%) of those with a positive family history were seropositive, compared to 1 out of 73 control women. Auto-antibodies were more frequently seen in the serum of breast cancer patients whose biopsies demonstrated overexpression of p53 protein. We conclude that auto-antibodies to p53 may have a role in the molecular characterisation of familial breast cancer.

Adult↗
PubMed1994

The relationship between serum p53 autoantibodies and characteristics of human breast cancer.

Sera from 182 newly diagnosed breast cancer patients were assayed for antibodies to p53 using an enzyme-linked immunosorbent assay (ELISA) method, and antibodies were detected in 48 (26%) compared with 1 out of 76 (1.3%) normal control volunteers (P = 0.0001). In breast cancer patients, autoantibodies were found in all stages of disease progression: carcinoma in situ, primary invasive breast cancer and in metastatic disease. In the subset of patients in whom sequential sera were assessed over a 6 month period, changes in the p53 antibody titres were observed. The presence of antibodies to p53 correlated positively with high histological grade (P = 0.0012) and a history of second primary cancer (six positive out of eight cases). The incidence of autoantibodies was lower in those patients with a first-degree relative with breast cancer (P = 0.046). Out of 68 patients, there was a significant correlation between positive p53 autoantibody status and the detection of p53 protein in the tissue sections by immunocytochemistry (P = 0.002). In the seronegative patients, positive p53 tumour staining was strongly associated with a family history of breast cancer (P = 0.009). The p53 protein overexpressed in heritable breast cancers may therefore be less immunogenic. The presence of p53 autoantibodies provides important additional information to immunochemistry and may identify patients with aggressive histological types of breast cancer.

Adult↗
PubMed1994

Effects of pentoxifylline and progesterone on human sperm capacitation and acrosome reaction.

This study was designed to test the effects of pentoxifylline and progesterone upon capacitation of fresh human spermatozoa. Capacitation and acrosomal integrity were assessed using the fluorescent probe chlortetracycline on spermatozoa co-stained with a supravital fluorescent dye, Hoechst 33258. Hyperactivated motility was measured using computer-assisted movement analysis. After exposure to pentoxifylline (1 mg/ml; 30 min), the fluorescent 'B' pattern, characteristic of capacitated, acrosome-intact cells, increased significantly (P < 0.01), though no increase in 'AR' pattern, characteristic of acrosome-reacted cells, was detected. There was a significant increase in hyperactive motility (P < 0.001). Exposure to progesterone (1 microgram/ml; 60 min) resulted in a significant increase in 'B' pattern (P < 0.05) and 'AR' pattern (P < 0.005), though no effect on the expression of hyperactivation was detected. No effect upon hyperactivation was detected on exposure of fresh or cryopreserved spermatozoa to a physiological range of progesterone concentrations (0.1-1000 ng/ml). Sequential exposure to pentoxifylline then progesterone resulted in a significant increase in 'B' pattern, acrosome loss and hyperactivation. Sperm viability was not affected in any treatment group. These observations suggest that pentoxifylline and progesterone affect capacitation through independent mechanisms. Stimulation of both capacitation and acrosome reaction resulted from sequential exposure to pentoxifylline and progesterone. This may have implications for sperm handling for assisted reproductive techniques.

Acrosome↗
PubMed1993

Granulocyte colony-stimulating factor supportive treatment following intensive chemotherapy in acute lymphocytic leukemia in first remission.

BACKGROUND: The efficacy of granulocyte colony-stimulating factor (G-CSF) in reducing neutropenia and its associated complications in adults with acute lymphocytic leukemia (ALL) undergoing intensive chemotherapy in first remission was evaluated. METHODS: Fourteen adult patients with ALL in first remission received intensive chemotherapy consisting of mitoxantrone 5 mg/m2 intravenously (IV) over 1 hour daily for 3 days, cytosine arabinoside (ara-C) 3 g/m2 IV over 2 hours every 12 hours x 4 on days 1 and 2, vincristine 2 mg IV on day 1, solumedrol 50 mg IV twice daily for 5 days, and G-CSF 5 micrograms/kg subcutaneously daily starting on day 4 until granulocyte recovery. Their outcome was compared with that of 14 consecutive patients who received the same intensification chemotherapy, but without G-CSF. The latter patients had been entered on the same ALL protocol from April 1990 through June 1991. RESULTS: G-CSF administration was associated with a significant shortening in the duration of neutropenia. The number of days to granulocyte recovery above 0.5 x 10(3)/microliters was 14 in the G-CSF group versus 18 days in the historical group (P < 0.001). Two episodes of documented infections were observed in the G-CSF group compared with four episodes in the historical group. Death during intensification therapy occurred in 2 of 14 patients in the historical group, but in none of the 14 patients receiving G-CSF. CONCLUSIONS: G-CSF as an adjunct to intensive chemotherapy in adults with ALL in first remission yielded positive results. Future studies incorporating growth factors supportive care during remission, induction, and consolidation may reduce treatment-related morbidity and mortality, increase the dose-intensity delivery of therapy, and potentially improve patient outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Pentoxifylline stimulates hyperactivation in human spermatozoa.

The effects of pentoxifylline on the movement characteristics of human spermatozoa incubated under capacitating conditions were examined using automated digital image analysis. Washed spermatozoa from cryopreserved and fresh normozoospermic, and fresh oligozoospermic semen were incubated in the presence of pentoxifylline (3.6 mM) for 30 min. In each group, pentoxifylline caused an increase in the average lateral head displacement and curvilinear velocity and a decrease in the linearity of progression. This related to a significant increase in the population of spermatozoa developing hyperactivation. The effect was maximal at between 15 and 75 min incubation. No detrimental effect on sperm vitality was demonstrated. It was shown that hyperactivation remained elevated compared with the control after washing pentoxifylline from the suspension. This effect was maintained for 1 h, but became insignificant after 3 h. These data demonstrate that pentoxifylline stimulates the development of hyperactivation in washed human spermatozoa, a phenomenon which may be of value in the treatment of some forms of male factor infertility.

Cryopreservation↗
PubMed1993

Chronic lymphocytic leukemia--correlation of response and survival.

Chronic lymphocytic leukemia (CLL) is considered to be an incurable hematologic malignancy using conventional therapy. Complete remissions (CR) were unusual with conventional approaches such as chlorambucil with or without prednisone or cyclophosphamide, vincristine, and prednisone (CVP). Pathologic complete remissions including negative bone marrow biopsies were seldom mentioned in the literature. Two parameter flow cytometry has demonstrated that CLL cells co-express CD5 and pan-B cell antigens such as CD19 and CD20. In addition, immunoglobulin gene rearrangement occurs predictably in B-cell CLL and can be used as a further marker of completeness of remission. The National Cancer Institute (NCI) has published criteria for complete remission which allow persistent lymphoid nodules to be present on the bone marrow biopsy and the patient can be considered in complete remission. Our group has considered these patients to have a nodular CR (Nod CR) to separate them from having a true remission on bone marrow biopsy (CR-bx). Thus bone marrow biopsy criteria, two parameter flow cytometry, and immunoglobulin gene rearrangement are now available for routine clinical application to re-define completeness of remission in CLL. With the use of fludarabine monophosphate (Fludara), complete and partial responses are obtained in 50-55% of previously treated patients with CLL and 75-80% of patients with previously untreated CLL. There was a strong correlation of probability of response with degree of previous therapy, stage of disease, age, hemoglobin level, platelet count, serum albumin and beta 2-microglobulin, and bone marrow infiltration with lymphocytes. Patients can be identified as being at high/low risk of achieving a complete or partial response.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1993

Phase II clinical trial of fludarabine in chronic lymphocytic leukemia on a weekly low-dose schedule.

The major complication during therapy of chronic lymphocytic leukemia (CLL) with the purine nucleotide analogue fludarabine is infection, which is also the main cause of morbidity and mortality in the disease. As the incidence of infectious episodes during therapy correlated with severity of neutropenia, stage of disease, and response to therapy, an effort was made to reduce therapy-related myelosuppression and improve response by altering the conventional therapy regimen. The protocol which yielded a response rate of 57% in previously treated patients with CLL consisted of five consecutive daily doses of 25-30 mg/m2 fludarabine given every three to four weeks. Based on observations from intracellular pharmacology studies it was hypothesized that repetitive single weekly doses of fludarabine would allow normal bone marrow cells to recover while maintaining cytotoxic levels in the leukemic cells. The cumulative four-week dose of the once-weekly regimen was approximately 80% of the original protocol. Eleven out of 46 evaluable patients (24%) responded to the therapy. Seven patients (15%) achieved a complete remission, and four (9%) a partial remission. While myelosuppression was reduced by about 30% compared with the original protocol, the incidence of febrile episodes was increased by 17%. Pretreatment serum IgG levels below the normal range correlated significantly with a high incidence of infectious episodes and with a short median survival time. These observations suggest that in addition to myelosuppressive therapy, disease related depressed immune function causes morbidity and mortality due to infections. The results further show that changes in the scheduling of the therapy regimen, associated with a slightly lower dose, resulted in reduced efficacy as measured by the response rate.

Adult↗
PubMed1993

A fos-lac Z transgenic mouse that can be used for neuroanatomic mapping.

Cellular immediate-early genes are rapidly induced by a diverse range of agents and conditions. Since many cIE genes encode known or potential transcription factors, they are believed to couple extracellular stimuli to long-lasting alterations in cellular phenotype through the regulation of gene transcription. In addition, the localization of the products of cIE genes has been used as a method for determining the cellular sites of action of particular agents in the nervous system. However, the methods of analysis are tedious, and the results may be ambiguous because of cross-reaction of reagents with related proteins. To further the utility of this approach, a bacterial gene encoding beta-galactosidase (lac Z) has been fused, in frame, into the fourth exon of c-fos, and this fos-lac Z fusion gene has been introduced into the germ line of mice. We have analyzed the expression of beta-galactosidase (under the control of the c-fos promoter) in the developing and adult nervous systems of these transgenic mice. As far as can be determined, the constitutive and stimulated expression of the transgene accurately reflects the expression of cognate c-fos in both cultured cells and the intact animal. This study has also revealed novel sites of constitutive and induced expression of c-fos that were overlooked using conventional analysis. In particular, constitutive expression of c-fos is associated with cells that are entering terminal differentiation and are destined to die. In addition, induced expression of the transgene in adult brain mirrors the pattern of neurotoxicity elicited by kainic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

fos-lacZ transgenic mice: mapping sites of gene induction in the central nervous system.

A transgenic mouse line containing a fos-lacZ fusion gene was derived in which beta-galactosidase activity identified cell populations expressing fos either constitutively or after stimulation. Seizures and light pulses induced nuclear lacZ activity in defined populations of neurons in vivo, and an array of neurotransmitters, including glutamate, induced the transgene in primary brain cultures. In unstimulated mice, the major sites of fos-lacZ expression were skin, hair follicle, and bone. fos-lacZ mice provide a new avenue for activity mapping studies based on gene expression.

Adrenal Glands↗