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Biomedical subjects

G R Taylor

Publications and source records attributed to G R Taylor.

At least 73 records · Page 4Linked to original sources
PubMed1993

Immune changes during short-duration missions.

Spaceflight materially influences the immune mechanism of humans and animals. Effects resulting from missions of less than 1 month are examined. Effects from longer missions are discussed in the companion paper by Konstantinova et al. Most immunology studies have involved analyses of subjects and samples from subjects obtained after flight, with the data being compared with similar data obtained before flight. These studies have demonstrated that short-duration missions can result in a postflight depression in blast cell transformation, major changes in cytokine function, and alterations in the relative numbers of immune cell populations. In addition to these post- vs. preflight studies, some data have been produced in flight. However, these in vitro analyses have been less than satisfactory because of differences between in-flight and ground-control conditions. Recently, both the U.S. and Russian space programs have started collecting in-flight, in vivo, cell-mediated immunity data. These studies have confirmed that the human cell-mediated immune system is blunted during spaceflight.

Humans↗
PubMed1993

Prognostic value of p53 overexpression and c-Ki-ras gene mutations in colorectal cancer.

BACKGROUND: Mutations in Ki-ras codon 12 and the p53 gene are common abnormalities in colorectal cancer. The occurrence of p53 overexpression and/or Ki-ras codon 12 mutations were analyzed in 100 colorectal adenomas to determine if they were related to patient survival. METHODS: p53 overexpression was identified by immunohistochemistry, and Ki-ras codon 12 mutations were detected using the polymerase chain reaction and a restriction enzyme digestion method. RESULTS: p53 overexpression was identified in 45% of tumors, with a higher frequency identified in DNA aneuploid and left-sided tumors than in DNA diploid and right-sided tumors. Mutations in Ki-ras codon 12 were identified in 24% of carcinomas. Individually, mutations in Ki-ras codon 12 or p53 overexpression were not prognostic indicators of survival. However, a statistically significant difference in survival was identified when these two oncogenic abnormalities were analyzed together. The median survival of patients whose tumors contained both oncogenic abnormalities was less than half of that of patients with either alteration alone or without either abnormality. CONCLUSIONS: Screening for multiple genetic abnormalities in colorectal cancers excised at surgery may prove to be a useful tool in determining prognosis.

Adenocarcinoma↗
PubMed1993

Rapid detection of allele loss in colorectal tumours using microsatellites and fluorescent DNA technology.

In order to investigate allele loss in colorectal tumours we have developed a rapid technique which overcomes most of the problems associated with radioactive Restriction Fragment Length Polymorphism (RFLP) analysis of allele loss. We utilise microsatellite length polymorphisms which are highly informative and are closely linked to loci of interest. Sequences containing microsatellites can be amplified from normal and tumour DNA pairs by a polymerase chain reaction (PCR) in which one of the primers is fluorescently labelled. This enables us to detect the products on polyacrylamide gels run on an automated DNA sequencer using dedicated software, by which results are automatically quantitated in terms of peak size, height, and area. Using this technique we have analysed 26 normal tissue: cancer pairs for allele loss at two loci linked to the adenomatous polyposis coli (APC) gene on chromosome 5q. Repeated assays yielded identical results for each pair. Allele loss was found in 10 out of 25 informative samples (40%).

Adenocarcinoma↗
PubMed1993

Diagnosis of complete molar pregnancy by microsatellites in archival material.

AIMS: To develop an assay which would determine the parentage of hydatidiform molar pregnancies. METHODS: DNA was extracted from formalin fixed, paraffin wax embedded tissue from hydatidiform molar pregnancies and spontaneous abortions after separation of chorionic villi and decidua. PCR amplification of dinucleotide repeat sequences ("microsatellites") was performed using three different primers. Products were radioactively labelled and visualised by autoradiography of dried polyacrylamide gels. RESULTS: With informative microsatellites, diagnostic patterns of amplification were obtained. Complete moles yielded either one or two microsatellites which differed from both maternal (decidual) microsatellites. Complete mole could be excluded by all the microsatellites showing alleles identical with those in maternal DNA. CONCLUSIONS: This technique offers a method of determining the presence of entirely paternal alleles in a molar pregnancy and thus confirming a complete hydatidiform mole.

Abortion, Spontaneous↗
PubMed1993

The clinical chemistry and immunology of long-duration space missions.

Clinical laboratory diagnostic capabilities are needed to guide health and medical care of astronauts during long-duration space missions. Clinical laboratory diagnostics, as defined for medical care on Earth, offers a model for space capabilities. Interpretation of laboratory results for health and medical care of humans in space requires knowledge of specific physiological adaptations that occur, primarily because of the absence of gravity, and how these adaptations affect reference values. Limited data from American and Russian missions have indicated shifts of intra- and extracellular fluids and electrolytes, changes in hormone concentrations related to fluid shifts and stresses of the missions, reductions in bone and muscle mass, and a blunting of the cellular immune response. These changes could increase susceptibility to space-related illness or injury during a mission and after return to Earth. We review physiological adaptations and the risk of medical problems that occur during space missions. We describe the need for laboratory diagnostics as a part of health and medical care in space, and how this capability might be delivered.

Aerospace Medicine↗
PubMed1992

Isolation of two distinct type I angiotensin II receptor genes.

A rat genomic Southern blot, probed with a type I angiotensin II receptor probe, demonstrated that two highly homologous type I angiotensin II receptors were present. A rat genomic library was subsequently screened and four clones were isolated. From restriction mapping, differential hybridization, polymerase chain reaction amplification and sequence analyses we have determined that there are two unique type I angiotensin II receptor genes. The first of these genes corresponds to the published rat vascular complementary DNA sequence; the second, corresponds to a novel receptor not previously described.

Amino Acid Sequence↗
PubMed1992

In vivo testing confirms a blunting of the human cell-mediated immune mechanism during space flight.

The cell-mediated immune (CMI) mechanism was evaluated in 10 space shuttle astronauts by measuring their delayed-type hypersensitivity response to seven common recall antigens. The Multitest CMI test system was used to administer antigens of tetanus, diphtheria, Streptococcus, Proteus, old tuberculin, Candida, and Trichophyton to the forearm 46 h before nominal mission termination; readings were conducted 2 h after landing. The mean number of reactions was reduced from 4.5 preflight to 3.0 inflight, and the mean reaction score was reduced from 21.4 to 13.7 mm inflight. The data presented suggest that the CMI system is still being degraded by space flight conditions on day 4 and that between day 5 and day 10, the depression maximizes and the system begins to adjust to the new conditions. The relation of these in vivo findings to previously reported in vitro results is discussed.

Aerospace Medicine↗
PubMed1992

Isolation and sequencing of CA/GT repeat microsatellites from chromosomal libraries without subcloning.

A method for the isolation of (CA)n microsatellites from chromosome-specific genomic libraries is described. Clones were first screened using a polynucleotide CA/GT probe. Those shown to contain CA repeats were plaque purified and either subcloned or the insert amplified directly using vector primers. Polymerase chain reaction products were then used to directly sequence the regions flanking CA repeats by using biotinylated primers that amplify cloned inserts outward from CA repeat containing regions of DNA to vector primers. This method provides rapid access to microsatellites from chromosomes or chromosome regions of interest.

Alleles↗
PubMed1992

Normobaric hypoxia stimulates endothelin-1 gene expression in the rat.

The current study tested the hypothesis that exposure to hypoxia enhances endothelin-1 (ET-1) gene expression and elevates circulating ET-1 levels in the rat. Rats were exposed to normobaric hypoxia (10% O2) or room air for 24 or 48 h. ET-1 in arterial blood was measured by radioimmunoassay. ET-1 gene transcript levels were measured by the slot blot technique on total RNA isolated from lung, right and left atria, right and left ventricles, kidney, spleen, liver, brain, main trunk of pulmonary artery, and thoracic aorta. Blots were probed with a 0.5 kb rat prepro ET-1 cDNA that does not cross-hybridize with mRNA for ET-2 or ET-3. Plasma ET-1 levels were increased significantly at 24 (10.03 +/- 2.33 pg/ml) and 48 h (14.02 +/- 3.44 pg/ml) of hypoxia compared with air controls (4.14 +/- 0.66 pg/ml). ET-1 mRNA levels were increased significantly (2-fold) in lung and right atrium after 48 h of hypoxia; no change was seen in organs perfused by the systemic vascular bed. These findings suggest that the hypoxia-induced increase in circulating ET-1 levels is mainly of pulmonary origin. A paracrine effect of ET-1 produced by lung endothelial cells could account for hypoxic pulmonary hypertension.

Animals↗
PubMed1992

Spaceflight alters immune cell function and distribution.

Experiments were carried out aboard COSMOS 2044 to determine the effects of spaceflight on immunologically important cell function and distribution. Control groups included vivarium, synchronous, and antiorthostatically suspended rats. In one experiment, rat bone marrow cells were examined in Moscow, for their response to recombinant murine granulocyte/monocyte colony-stimulating factor (GM-CSF). In another experiment, rat spleen and bone marrow cells were stained in Moscow with a variety of antibodies directed against cell surface antigenic markers. These cells were preserved and shipped to the United States for analysis on a flow cytometer. Bone marrow cells from flown and suspended rats showed a decreased response to granulocyte/monocyte colony-stimulating factor compared with bone marrow cells from control rats. Of the spleen cell subpopulations examined from flown rats, only those cells expressing markers for suppressor-cytotoxic T- and helper T-cells showed an increased percentage of stained cells. Bone marrow cells showed an increase in the percentage of cells expressing markers for helper T-cells in the myelogenous population and increased percentages of anti-asialo granulocyte/monocyte-1-bearing interleukin-2 receptor-bearing pan T- and helper T-cells in the lymphocytic population. Cell populations from rats suspended antiorthostatically did not follow the same pattern of distribution of leukocytes as cell populations for flown rats. The results from COSMOS 2044 are similar, but not identical, to earlier results from COSMOS 1887 and confirm that spaceflight can have profound effects on immune system components and activities.

Animals↗
PubMed1992

Effect of spaceflight on natural killer cell activity.

The effects of spaceflight on immune cell function were determined in rats flown on COSMOS 2044. Control groups included vivarium, synchronous, and antiorthostatically suspended rats. The ability of natural killer cells to lyse two different target cell lines was determined. Spleen and bone marrow cells obtained from flight rats showed significantly inhibited cytotoxicity for YAC-1 target cells compared with cells from synchronous control rats. This could have been due to exposure of the rats to microgravity. Antiorthostatic suspension did not affect the level of cytotoxicity from spleen cells of suspended rats for YAC-1 cells. On the other hand, cells from rats flown in space showed no significant differences from vivarium and synchronous control rats in cytotoxicity for K-562 target cells. Binding of natural killer cells to K-562 target cells was unaffected by spaceflight. Antiorthostatic suspension resulted in higher levels of cytotoxicity from spleen cells for 51Cr-labeled K-562 cells. The results indicate differential effects of spaceflight on function of natural killer cells. This shows that spaceflight has selective effects on the immune response.

Animals↗
PubMed1991

c-Ki-ras gene mutations in dysplasia and carcinomas complicating ulcerative colitis.

One hundred and nine samples comprising carcinomas, adenomas, dysplastic, inflamed and normal mucosa from patients with sporadic colon cancer and ulcerative colitis (UC) were analysed for c-Ki-ras mutations. DNA was extracted from archival paraffin-embedded material, amplified using the polymerase chain reaction (PCR) and the PCR products analysed using restriction enzyme digestion. Forty-two per cent (14/33) of the sporadic carcinoma controls contained Ki-ras codon 12 mutations in contrast to 24% (8/33) of ulcerative colitis carcinomas. A significantly higher c-Ki-ras mutation rate was observed in rectal carcinomas (72%) in comparison to colonic carcinomas (28%) in control patients (P less than 0.04), while the opposite was observed in UC patients. The difference between the incidence of c-Ki-ras mutations in rectal carcinomas in UC (9%) and in sporadic rectal carcinomas (72%) was also significant (P less than 0.01). This lower prevalence rate and different site distribution of c-Ki-ras mutations in UC carcinomas compared to sporadic carcinomas suggests that specific genetic differences may underlie the causation of carcinomas arising in these situations.

Codon↗
PubMed1991

Effect of microgravity modeling on interferon and interleukin responses in the rat.

Rats were placed in whole-body harness suspension in three configurations: antiorthostatic hypokinetic/hypodynamic suspension (AAH) to induce headward body fluid redistribution and unload the limbs, orthostatic hypokinetic/hypodynamic suspension (OHH) to unload the limbs without fluid redistribution, and harness restraint (HR) to produce the restraint stress of the model without fluid redistribution or musculoskeletal disuse. AHH and OHH suspension transiently increased interferon-gamma (IFN-gamma) production in response to the mitogen concanavalin A. Harness restraint alone did not affect IFN-gamma response. However, both suspension modeling and harness restraint caused a transient reduction in interleukin-1 (IL-1) and IL-2 responses to mitogen. This suggests that factors associated with musculoskeletal unloading affected IFN-gamma responses, while IL-1 and IL-2 responses were affected by the physiological stress of restraint.

Animals↗
PubMed1991

Direct polymerase chain reaction test for detection of Helicobacter pylori in humans and animals.

We designed a polymerase chain reaction (PCR) for amplifying the Helicobacter pylori gene encoding 16S rRNA. Primers for the specific detection of H. pylori were designed for areas of the 16S rRNA gene in which there is the least sequence homology between H. pylori and its closest relatives. The specificity of detection was confirmed by ensuring that the primers did not amplify DNA extracts from the campylobacters H. cinaedi, H. mustelae, and Wolinella succinogenes, which are the closest relatives of H. pylori, as determined by 16S rRNA sequencing. Serial dilution experiments revealed the detection of as little as 0.1 pg of DNA by PCR and 0.01 pg by nested PCR. H. pylori DNA was detected successfully in clinical paraffin-embedded and fresh gastric biopsy specimens from patients positive for the bacterium and also in fecal suspensions seeded with the organism. The DNA from the nonculturable coccoid form of H. pylori was also identified by the primers. Universal primers designed for highly conserved areas on the 16S rRNA gene enabled large amplification products to be produced for direct sequencing analysis. Gastric bacteria resembling H. pylori have been isolated from animals. DNA of these animal gastric bacteria amplified with H. pylori-specific primers yielded PCR products identical to those from human isolates of H. pylori, as confirmed by the use of a 20-base radiolabelled probe complementary to an internal sequence flanked by the H. pylori-specific primers. The results of PCR amplification and partial 16S rRNA gene sequence analysis strongly support the contention that the gastric organisms previously recovered from a pig, a baboon, and rhesus monkeys are H. pylori.

Animals↗
PubMed1990

Dosage prescribing and plasma oxipurinol levels in patients receiving allopurinol therapy.

This study examined dosage prescribing patterns and steady-state oxipurinol plasma concentrations in 66 patients receiving chronic allopurinol therapy. Most patients (65%) were taking 300 mg allopurinol daily, although renal impairment was common. Using published guidelines, it was estimated that 35% of patients were receiving excessive dosages of allopurinol. Consequently, the plasma oxipurinol concentrations were often very high (mean (SD) was 156 (109) mumol.l-1). Accumulation of oxipurinol was inversely related to renal function. Plasma concentrations of oxipurinol and urate were not significantly related. However, most patients with oxipurinol concentrations of up to 100 mumol.l-1 had urate concentrations within the normal reference range.

Aged↗