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Biomedical subjects

B Smith

Publications and source records attributed to B Smith.

At least 19 recordsLinked to original sources
PubMed1995

Patterns of splice variant CD44 expression by normal human urothelium in situ and in vitro and by bladder-carcinoma cell lines.

CD44 core and splice variant exon expression was investigated in the stratified transitional epithelium of the urinary tract and in normal and malignant bladder epithelial cell lines in vitro. Antibodies against core CD44 epitopes and splice exon variants v3, v4/5, v5 and v6 showed an intense reaction in the basal and lower intermediate urothelial cell layers, which was consistently lost from the upper intermediate and superficial cell layers. Seven independent cell lines established from normal human urothelium expressed complex multiple-spliced CD44 mRNA transcripts when tested by RT-PCR and were positive with antibodies against CD44 core epitopes and splice variants v3, v4/5, v5 and v6. Of the 13 bladder-carcinoma cell lines, all were positive for CD44 core. The more differentiated cell lines had retained some splice-variant antibody reactivity and showed multiple but less complex CD44 mRNA transcript patterns, compared with normal cells. Anaplastic cell lines did not react with variant antibodies and did not contain multiple-spliced CD44 transcripts. These data suggest that loss of alternatively-spliced CD44 may reflect a selection pressure in the evolution of anaplastic bladder cancers.

Antigens, Neoplasm↗
PubMed1995

Ambulatory blood pressure in pregnancy: comparison of the Spacelabs 90207 and Accutracker II monitors with intraarterial recordings.

OBJECTIVE: Our purpose was to compare systolic and diastolic blood pressures obtained with the Spacelabs 90207 (Spacelabs Medical Products, Dee Why, Australia) or Accutracker II (Suntech Medical Instruments, Melbourne, Australia) ambulatory blood pressure monitoring devices with intraarterial blood pressures in pregnant women. STUDY DESIGN: Direct (intraarterial) and resting blood pressures with the ambulatory blood pressure monitoring device were compared in 39 pregnant women (14 Accutracker II and 25 Spacelabs 90207). RESULTS: The Accutracker II device underestimated direct systolic pressure by -9 (-13, -3) mm Hg (median, interquartile range) (p = 0.028) but gave similar diastolic pressure. The Spacelabs 90207 device gave similar systolic pressures but overestimated direct diastolic pressure by 7 (2, 12) mm Hg (p < 0.001). Variability for systolic and diastolic blood pressures within subjects was similar with the two devices. Both received poor gradings by standards of the British Hypertension Society and did not meet criteria of the Association for the Advancement of Medical Instrumentation, with intraarterial recordings used as the reference. CONCLUSIONS: The Accutracker II device significantly underestimated resting direct systolic pressure, whereas the Spacelabs 90207 device significantly overestimated resting direct diastolic pressure in pregnant women. Although poor gradings were achieved for both devices when intraarterial pressures were used as the reference, this is similar to comparisons of routine mercury sphygmomanometry with intraarterial recordings and does not mean these devices are unsuitable for use in pregnancy.

Blood Pressure Monitoring, Ambulatory↗
PubMed1995

Loss of cyclin-dependent kinase inhibitor genes and chromosome 9 karyotypic abnormalities in human bladder cancer cell lines.

Loss of cell cycle control through the structural or functional aberration of checkpoint genes and their products is a potentially important process in carcinogenesis. In this study, a panel of well-characterised established human bladder cancer cell lines was screened by the polymerase chain reaction for homozygous loss of the cyclin-dependent kinase inhibitor genes p15, p16 and p27. The results demonstrate that, whereas there was no genetic loss of p27, homozygous deletion of both p15 and p16 genes occurred in seven of 13 (54%) independent bladder cell lines tested. Differential loss of either the p15 or p16 gene was not seen. The p15 and p16 genes are known to be juxtaposed on chromosome 9p21 at the locus of a putative tumour-suppressor gene involved in the initiation of bladder cancer. Cytogenetic analysis of the cell lines revealed karyotypes ranging from near diploid to near pentaploid with complex rearrangements of some chromosomes and a high prevalence of chromosome 9p rearrangements, although all cell lines contained at least one cytogenetically normal 9p21 region. These observations support a role for p15/p16 gene inactivation in bladder carcinogenesis and/or the promotion of cell growth in vitro and lend support to the hypothesis that homozygous deletion centred on 9p21 is a mechanism by which both p15 and p16 genes are co-inactivated.

Base Sequence↗
PubMed1995

Detection of epithelial cancer cells in peripheral blood by reverse transcriptase-polymerase chain reaction.

Circulating cancer cells in the blood play a central role in the metastatic process. Their number can be very small and techniques for their detection need to be both sensitive and specific. Polymerase chain reaction (PCR) has been successfully used to detect small numbers of tumour cells in haematological cancer in which abnormalities in DNA are sufficiently consistent to make this possible. For most solid tumours this not yet feasible. However, we have found that reverse transcriptase (RT)-PRC for tissue-specific gene expression is a useful technique for identifying small numbers of circulating cells in melanoma and neuroblastoma patients. In this report we describe detection of colon carcinoma cells by RT-PCR using CK 20 mRNA as a marker. Unlike other cytokeratin genes examined (CK 8 and CK 19), CK 20 was not transcribed in normal haematopoietic cells. This suggests a role for RT-PCR in the detection of colon carcinoma metastasis in blood and bone marrow, using CK 20 as the target gene. Future analysis of clinical material will determine the clinical significance of this technique.

Adenocarcinoma↗
PubMed1995

Further studies of the binding specificity of the leukocyte adhesion molecule, L-selectin, towards sulphated oligosaccharides--suggestion of a link between the selectin- and the integrin-mediated lymphocyte adhesion systems.

This communication is concerned with the binding specificity of the leukocyte-adhesion molecule L-selectin (leukocyte homing receptor) towards structurally defined sulphated oligosaccharides of the blood group Le(a) and Le(x) series, and of the glycosaminoglycan series heparin, chondroitin sulphate and keratan sulphate. The recombinant soluble form of the rat L-selectin (L-selectin-IgG Fc chimera) investigated here was shown previously to bind to lipid-linked oligosaccharides 3-O, 4-O and 6-O sulphated at galactose, such as sulphatides and a mixture of 3-sulphated Le(a)/Le(x) type tetrasaccharides isolated from ovarian cystadenoma, as well as to the HNK-1 glycolipid with 3-O sulphated glucuronic acid. In the present study, the L-selectin investigated in both chromatogram binding and plastic microwell binding experiments using neoglycolipids was found to bind to the individual 3-sulphated Le(a) and Le(x) sequences (penta-, tetra- and trisaccharides), and with somewhat lower intensities to their non-fucosylated analogues. Glycosaminoglycan disaccharides of keratan sulphate, heparin and chondroitin sulphate types were also bound by L-selectin in one or both assay systems, leading to the conclusion that clustered glycosaminoglycan oligosaccharides with 6-O sulphation of N-acetylgalactosamine, N-acetylglucosamine or glucosamine, 4-O sulphation of N-acetylgalactosamine, 2-O sulphation of uronic acid, N-sulphation of glucosamine and, to a lesser extent, the non-sulphated uronic acid-containing disaccharides, can support L-selectin adhesion. As inflammatory chemokines (short-range stimulators of lymphocyte migration which trigger integrin activation) are known to bind to endothelial glycosaminoglycans, we propose that the binding of the lymphocyte membrane L-selectin to endothelial glycosaminoglycans may provide a link between the selectin-mediated and integrin-mediated adhesion systems in leukocyte extravasation cascades. The possibility is also raised that lymphocyte L-selectin interactions with glycosaminoglycans may contribute to pathologies of glycosaminoglycan-rich tissues, e.g. cartilage loss in rheumatoid arthritis and inflammatory lesions of the cornea.

Animals↗
PubMed1995

Acute regional myocardial ischemia and recovery after cardiopulmonary bypass: effects of intensity of antecedent ischemia.

Aortic cross-clamping with inadequate myocardial preservation has been shown to cause postoperative decreases in myocardial performance following coronary artery bypass graft surgery. We have demonstrated a mild decrement in myocardial beta-receptor function associated with cold cardioplegia in a normal animal model; in normal human hearts, however, response to beta-adrenergic inotropic stimulation was diminished significantly. Beta-receptor dysfunction also is associated with chronic myocardial ischemia that is associated with severe ischemic heart disease. Although the change in beta-receptor function with acute regional myocardial ischemia associated with severe ischemic heart disease is not understood fully, we found that the intensity of regional ischemia significantly affects functional recovery after cardiopulmonary bypass (CPB). Myocardial stunning does not appear to be significant in this dysfunction; however, alterations in beta-receptor density and function may play a critical role in post-CPB ventricular function.

Animals↗
PubMed1995

The prenatal exclusion test for Huntington's disease: experience in the west of Scotland, 1986-1993.

Information about the prenatal exclusion test for Huntington's disease (HD) has been given to an unselected series of couples who attended the genetic counselling clinic from 1986 onwards. Ten couples underwent 13 prenatal tests during this period with expressed intention of stopping a pregnancy if the result indicated a high risk (almost 50%) that the fetus carried the HD gene. Nine fetuses at nearly 50% risk of carrying the HD gene were identified but only six such pregnancies were terminated. In each of three high risk pregnancies which continued, the mother made a "final hour" decision not to undergo the scheduled, first trimester termination. In our experience, late reversal of a previous decision to undergo first trimester pregnancy termination for a genetic indication is uniquely frequent among couples who have undergone the prenatal exclusion test for HD.

Adult↗
PubMed1995

Bronchial hygiene therapy.

Bronchial hygiene therapy is useful and effective in the presence of careful patient evaluation, clear definition of therapeutic goals, and application of appropriate modalities. This article defines the variable bronchial hygiene modalities and discusses their indications, contraindications, and applications. Prophylactic and therapeutic bronchial hygiene modalities, diagnostic methods associated with bronchial hygiene therapy, inhaled antibiotic therapy, and therapist driven protocols are also addressed.

Administration, Inhalation↗
PubMed1995

PGE1 suppresses the induction of collagen synthesis by transforming growth factor-beta 1 in human corpus cavernosum smooth muscle.

Collagen synthesis has been examined in primary cultures of human corpus cavernosum smooth muscle cells (HCCSMC), the major mesenchymal cell type of the corpus cavernosum. These cultures were grown from human surgical specimens and characterized by morphological and biochemical characteristics. These cells express mRNA for transforming growth factor-beta 1 (TGF-beta 1), a major regulator of extracellular matrix synthesis, as well as all three subtypes of TGF-beta receptors. Human corpus cavernosum smooth muscle cells primarily synthesize types I and III fibrillar collagen. Treatment of HCCSMC with exogenous TGF-beta 1 (80 pM.) induced a 2.5- to 4.5-fold increase in the synthesis of types I and III collagen and resulted in detectable levels of type V/XI collagen. Treatment of HCCSMC with the eicosanoid PGE1 in combination with TGF-beta 1 suppressed the induction of collagen synthesis by TGF-beta 1 in a dose-dependent manner with concomitant decreases in types I, III and V/XI collagen. The expression of TGF-beta 1 mRNA as well as types I and II TGF-beta receptors was induced by exogenous TGF-beta 1. Transforming growth factor-beta 1 mRNA induction was suppressed by PGE1. These data suggest that prostaglandins and TGF-beta 1 may play a key role in modulation of collagen synthesis in the corpus cavernosum, and in the regulation of fibrosis of the corpus cavernosum.

Alprostadil↗
PubMed1994

Neuroblastoma cell detection by reverse transcriptase-polymerase chain reaction (RT-PCR) for tyrosine hydroxylase mRNA.

The presence of tumour cells in peripheral blood of neuroblastoma patients is of considerable clinical importance. Nucleic acid amplification offers an opportunity to detect very small numbers of such cells, but in neuroblastoma a frequent specific abnormality in the tumour DNA suitable for this purpose has yet to be identified. To facilitate the detection of such cells we have developed RT-PCR using tyrosine hydroxylase (TH) as a tissue-specific target gene. TH mRNA was detected in 3 neuroblastoma cell lines and in all neuroblastoma tumours examined, but was undetectable in peripheral blood from children without neuroblastoma. The method was highly sensitive, detecting 1-10 neuroblastoma cells per 10(7) blood cells. Thirty blood samples from 24 patients were analysed and results were compared with known disease status. At diagnosis 4/7 patient blood specimens were positive; the four positive samples were from stage-4 patients. In blood samples from these patients 6-8 weeks after the initiation of treatment, TH mRNA was undetectable. Of 7 samples taken at the time of clinical relapse, 5 were positive; 4 of these were from patients with evidence of disseminating disease. Of 16 blood samples from disease-free patients, 14 were negative and 2 were positive. One positive patient in this group subsequently had a clinical relapse. These results show that this technique is of value for detecting neuroblastoma cells in peripheral blood. The significance of these cells at diagnosis, during treatment or on follow-up requires further evaluation.

Base Sequence↗