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Biomedical subjects

A Watson

Publications and source records attributed to A Watson.

At least 91 records · Page 5Linked to original sources

Electrostatic forces on the surface of metals as measured by atomic force microscopy.

Electrostatic forces play an important role in modulating the interaction of plasma proteins and blood cellular components with the surface of the vascular endothelium. Based on the concept that electrostatic forces residing on the surface of metal intravascular prostheses, such as the stent, also are critical in influencing blood interactions with those surfaces and the vascular wall, these studies were designed to measure these forces on 4 metals using atomic force microscopy (AFM). AFM measurements performed in a low saline aqueous medium at physiological pH indicate a similar net electronegative surface charge level for gold and 316l stainless steel that is significantly higher than the level measured on an electropolished Nitinol surface. Heat oxidation of the Nitinol surface increased the overall electronegativity and created a more homogeneous surface charge distribution. This study demonstrates that AFM force measurements can be a valuable approach to understanding the electrostatic surface of metallic as well as other biomaterials that may be important in understanding how these surfaces influence vascular healing at intravascular interventional sites.

Biocompatible Materials↗

Macrophage inflammatory protein 1alpha attenuates the toxic effects of temozolomide in human bone marrow granulocyte-macrophage colony-forming cells.

Macrophage inflammatory protein 1alpha (MIP-1alpha) is a chemokine that may act principally by preventing hemopoietic cells from entering G1, thereby attenuating the cytotoxic effects of cell cycle-specific chemotherapeutic agents. Here we examine the effect of MIP-1alpha on the sensitivity of human granulocyte-macrophage hemopoietic progenitor cells (granulocyte-macrophage colony-forming cells; GM-CFCs) with the cytotoxic effects of antitumor agents that act mainly via alkylation at the O6 position of guanine in DNA. Mononuclear cell preparations from human bone marrow were used in an in vitro GM-CFC colony-forming assay. The GM-CFC survival from individual patients displayed a range of sensitivities to the methylating agent temozolomide [(Tz) 20-55% survival at 10 microg/ml Tz]. However, in all 16 cases, MIP-1alpha (50 ng/ml) protected against GM-CFC killing: survival in the presence of MIP-1alpha ranged from 65-97% at 10 microg/ml Tz, with GM-CFCs being 1.5-4.5-fold more resistant than control cells from the same patient. The highest levels of protection were seen in the GM-CFCs with the highest sensitivity in the absence of MIP-1alpha. Similar degrees of protection were seen for the methylating agent streptozotocin, but no protection was detected for the chloroethylating agents carmustine or mitozolomide in the samples for which there was protection against the toxic effects of Tz. Whereas the mechanism of this effect remains to be established, the results may have potential immediate clinical application in the attenuation of hematological toxicity after administration of methylating antitumor agents.

Antineoplastic Agents, Alkylating↗

Viral burden and disease progression in rhesus monkeys infected with chimeric simian-human immunodeficiency viruses.

To determine the role of viral burden in simian-human immunodeficiency virus (SHIV)-induced disease, cellular provirus and plasma viral RNA levels were measured after inoculation of rhesus monkeys with four different SHIVs. These SHIVs included SHIV-HXBc2 and SHIV-89.6, constructed with env, tat, rev, and vpu derived from either cell line-passaged or primary patient isolates of human immunodeficiency virus type 1; the viral quasispecies SHIV-89.6P derived after in vivo passage of SHIV-89.6; and a molecular clone, SHIV-KB9, derived from SHIV-89.6P. SHIV-HXBc2 and SHIV-89.6 are nonpathogenic in rhesus monkeys; SHIV-89.6P and SHIV-KB9 cause rapid CD4(+) T cell depletion and an immunodeficiency syndrome. Relative SHIV provirus levels were highest during primary infection in monkeys infected with SHIV-89.6P, the virus that caused the most rapid and dramatic CD4(+) T cell depletion. However, by 10 weeks postinoculation, provirus levels were similar in monkeys infected with the pathogenic and nonpathogenic chimeric viruses. The virus infections that resulted in the highest peak and chronic viral RNA levels were the pathogenic viruses SHIV-89.6P and SHIV-KB9. SHIV-89. 6P uniformly caused rapid and profound CD4(+) T cell depletion and immunodeficiency. Infection with the SHIV-KB9 resulted in very low CD4(+) T cell counts without seroconversion in some monkeys and a substantial but less profound CD4(+) T cell depletion and rapid seroconversion in others. Surprisingly, the level of plasma viremia did not differ between SHIV-KB9-infected animals exhibiting these contrasting outcomes, suggesting that host factors may play an important role in AIDS virus pathogenesis.

Acquired Immunodeficiency Syndrome↗

Role of p53 assessment in management of Barrett's esophagus.

The risk of developing gastroesophageal adenocarcinoma is increased in patients with Barrett's esophagus. The management of dysplasia in Barrett's esophagus remains controversial. Understanding of the sequence of events preceding malignancy is essential before screening protocols for early diagnosis and preventive measures can be implemented. The aim of this review is to examine the published data on the role p53 assessment may play in the management of Barrett's esophagus. Relevant papers were identified by an extensive text word search of the Medline database and a review of quoted articles. The p53 abnormality occurs more frequently in highly dysplastic epithelium than in nondysplastic epithelium. However, the retrospective nature of most of the available data could be a significant confounding factor. Our current knowledge suggests that p53 protein overexpression does not seem to predict future progression to cancer or determine disease outcome. The p53 abnormality alone can not be reliably used to predict progression of Barrett's esophagus to cancer. We must await long-term evaluation of patients to determine the percentage of patients with p53 gene abnormality, and nondysplastic Barrett's who will progress to dysplasia or carcinoma. Large randomized controlled long-term follow-up studies are much needed.

Adenocarcinoma↗

Contact or immersion technique for axial length measurement?

PURPOSE: The purpose of the present study was to determine whether contact and immersion A-scan techniques produce comparable measures of the magnitude of eye axial length. METHOD: A prospective study in which 225 consecutive patients scheduled for cataract surgery in a private day surgery setting had axial lengths measured with an Alcon Ocuscan machine (Alcon Australia, Frenchs Forest, NSW, Australia) using both contact and immersion techniques. Twelve patients had both techniques repeated on a separate occasion. RESULTS: Measurements of eye axial length obtained by the immersion technique averaged 0.1 mm longer than those obtained by the contact technique. A difference in axial length values was confirmed in eyes subjected to repeated measurements. CONCLUSIONS: Both techniques give consistent results, but the difference between axial lengths measured by the two techniques has implications for choice of intra-ocular lens power.

Anthropometry↗

In-vivo measurement of intrauterine gases and acid-base values early in human pregnancy.

A new multiparameter sensor that combines electrochemical and fibre-optic technology was used for continuous in-vivo investigation of pH, carbon dioxide partial pressure (PCO(2)), oxygen partial pressure (PO(2)), bicarbonate concentration (HCO(3)(-)), base excess, and oxygen saturation (O(2)Sat) early in human pregnancy. The sensor was inserted into the amniotic cavity and the placental bed of 16 pregnancies at 10-15 weeks gestation, before termination under general anaesthesia. Amniotic fluid and retroplacental blood from the same site were also aspirated and analysed by means of cartridges and a portable blood gas analyser. Eleven series of measurements were obtained. The variation in measurements over the 5 min of monitoring was </=10% for all parameters. The sensor was damaged during insertion into the amniotic cavity in one case and in the placental bed in four cases. Measurements of PO(2) in both the amniotic cavity and the placental bed and of pH in the placental bed were higher using the cartridges than in vivo. The results indicated that in-vivo monitoring of fetoplacental gas and acid-base with a sensor is stable and accurate. Such technology will be helpful in improving our understanding of the fetoplacental metabolism in normal and complicated pregnancies.

Acid-Base Equilibrium↗

Effect of inflammatory mediators on the electrophysiology of the human oviduct.

The effects of histamine and other inflammatory mediators on the electrophysiology and intracellular free calcium ([Ca(2+)](i)) of human oviductal epithelial cells, grown as a polarized layer in primary culture, were studied. Transepithelial potential difference (PD) and short-circuit current (I(scc)) were recorded using a modified Ussing chamber. Resistance (R) was calculated from the measurements of PD and I(scc). Basally applied histamine produced transient increases in PD and I(scc) with a small decrease in R. The histamine effect was reduced by triprolidine (H(1) receptor antagonist) but was unaffected by H(2) (ranitidine) or H(3) (thioperamide) receptor antagonists. Blockers of Na(+), K(+), or Na(+)/K(+)/2Cl(-) channels did not affect histamine action. Blockers of Cl(-)/HCO(3)(-) channels or Ca(2+) channels reduced the histamine effect. Platelet activating factor (PAF), applied apically, increased PD and I(scc). Histamine produced a transient increase in fluorescence of Fura 2-AM dye, indicating an increase in [Ca(2+)](i). Triprolidine pretreatment inhibited histamine-stimulated [Ca(2+)](i) increase. Cimetidine, (H(2) receptor antagonist), ranitidine, or thioperamide reduced the histamine effect. Histamine increased contractions of both circular and longitudinal smooth muscles in oviduct segments, an effect that was antagonized by triprolidine or thioperamide but not by ranitidine. Histamine's action on Ca(2+) and Cl(-) movements may adversely affect oviductal fluid production and decrease fertility. PAF's effects on Cl(-) movements may be important for normal embryo transport.

Alprostadil↗

An initial comparison of nine centres registering patients with the UK National Barrett's Oesophagus Registry (UKBOR).

Initial data from the first nine hospitals registering at least 50 patients each with UKBOR were analysed. This involved 2102 Barrett's oesophagus (BO) cases (M1261:F841), mean 234 patients per centre (range 73-636) and M:F ratio 1.5 (range 1.1-2.3). There was an equal geographical distribution of the hospitals, three each in the north of the country (N), Midlands (Mid) and the south of the country (S). The catchment populations varied from 145,000 to 450,000. The M:F ratio for N, Mid and S was 1.6, 1.3, 1.7, respectively. The mean age at diagnosis in males was 62.0 years (range 53.2-66.3) and in females 67.6 years (range 59.3-73.4), with little geographical variation. The age distribution varied somewhat between the centres; the peak age for males being 40-49 years in one northern hospital, 60-69 years in seven others and 70-79 years in one hospital. For females it was 60-69 years and 70-79 years in each of four hospitals, and 80-89 years in one. The BO diagnosis rate in the under 50s was fairly constant; F mean 14% (range 0-23%); M (eight centres) mean 23% (range 16-27%). However, in one northern centre it was much higher (43%). Information on patients with a diagnosis of oesophageal adenocarcinoma (AC) was available from seven centres. A total of 59 AC were diagnosed (M44:F15, ratio 2.9). The overall mean rate of AC in BO was 3.6% (range 0.5-7.5%). Minor variations in BO patient characteristics may have been due to the hospitals' different policies on diagnostic and reporting criteria. However, the much higher percentage of men under age 50 in the one N centre may reflect a genuine difference in diet and lifestyle, or possibly genetic susceptibility.

Adenocarcinoma↗

Monosomy X as the sole cytogenetic abnormality in acute lymphoblastic leukemia: a report of two new patients.

Monosomy X as the sole acquired cytogenetic abnormality is usually found in myeloid hematological malignancies, especially those with myelodysplastic features. Only three cases of acute lymphoblastic leukemia (ALL) with this abnormality have been previously reported. We add two cases to this series and comment on the likelihood of a tumor suppressor gene being located on the X chromosome.

Adolescent↗