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Biomedical subjects

R M James

Publications and source records attributed to R M James.

At least 19 recordsLinked to original sources
PubMed2006

The investigation and management of chronic neutropenia in children.

Unravelling the cause of a neutropenia poses a complex diagnostic challenge. The differential diagnosis ranges from life threatening disease to transient benign causes of little clinical significance. This review offers a practical guide to investigating the neutropenic child, and highlights features that merit specialist referral. Therapeutic options, the role of long term follow up, and the complications of severe chronic neutropenia are considered.

Child↗
PubMed2003

Regulation of pulmonary and systemic bacterial lipopolysaccharide responses in transgenic mice expressing human elafin.

The control of lung inflammation is of paramount importance in a variety of acute pathologies, such as pneumonia, the acute respiratory distress syndrome, and sepsis. It is becoming increasingly apparent that local innate immune responses in the lung are negatively influenced by systemic inflammation. This is thought to be due to a local deficit in cytokine responses by alveolar macrophages and neutrophils following systemic bacterial infection and the development of a septic response. Recently, using an adenovirus-based strategy which overexpresses the human elastase inhibitor elafin locally in the lung, we showed that elafin is able to prime lung innate immune responses. In this study, we generated a novel transgenic mouse strain expressing human elafin and studied its response to bacterial lipopolysaccharide (LPS) when the LPS was administered locally in the lungs and systemically. When LPS was delivered to the lungs, we found that mice expressing elafin had lower serum-to-bronchoalveolar lavage ratios of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), macrophage inflammatory protein 2, and monocyte chemoattractant protein 1, than wild-type mice. There was a concomitant increase in inflammatory cell influx, showing that there was potential priming of innate responses in the lungs. When LPS was given systemically, the mice expressing elafin had reduced levels of serum TNF-alpha compared to the levels in wild-type mice. These results indicate that elafin may have a dual function, promoting up-regulation of local lung innate immunity while simultaneously down-regulating potentially unwanted systemic inflammatory responses in the circulation.

Animals↗
PubMed2003

Fulminant Crohn's colitis after allogeneic stem cell transplantation.

We report a case of fulminant Crohn's colitis that occurred following non-myeloablative allogeneic stem cell transplantation for Hodgkin's lymphoma. Adoptive transfer of inflammatory bowel disease by haematopoietic cells is recognised in several animal models of inflammatory bowel disease and remission of Crohn's disease has been reported in patients who have received a bone marrow transplant. However, adoptive transfer of Crohn's disease susceptibility leading to phenotypic manifestation of the disease after transplantation has not been previously reported. Having ruled out an infective cause of a colitis in this case, we speculated that adoptive transfer of Crohn's disease may have occurred and performed a genetic analysis of known susceptibility loci for significant donor-recipient mismatches. The donor and recipient had several haplotype mismatches in HLA class III genes at the IBD3 locus. In addition, the donor (but not the recipient) had a polymorphism of the 5' UTR of NOD2/CARD15 that may be associated with Crohn's disease. This case highlights the question of whether adoptive transfer of Crohn's disease can occur between allogeneic stem cell transplant donor and recipient, in a similar fashion to that reported for other autoimmune diseases. This report should also stimulate debate regarding the need for stem cell transplant donor screening for inflammatory bowel disease.

5' Untranslated Regions↗
PubMed2001

Mutant K-ras enhances apoptosis in embryonic stem cells in combination with DNA damage and is associated with increased levels of p19(ARF).

The roles of K-ras in neoplasia are not entirely understood, although there is evidence that K-ras affects susceptibility to apoptosis, modulating survival of DNA damaged cells which would otherwise be eliminated. In this study, we investigated the effects of mutant K-ras on apoptosis in vitro following DNA damage. To avoid complications resulting from mutations in other cancer-related genes and from the presence of endogenous K-ras, we derived K-ras null embryonic stem cells. Expression of either wild-type or mutant K-ras was reconstructed by stable plasmid transfection. The cell lines were treated with etoposide, cisplatin and UV radiation and apoptosis measured flow cytometrically. Mutant K-ras potentiated the effect of etoposide-derived DNA damage by increasing apoptosis, whereas absence of K-ras had the opposite effect. This pattern was similar but less marked with cisplatin, whereas UV yielded no difference in apoptosis with regard to K-ras status, suggesting that the effect of K-ras on apoptosis is dependent on the nature of the DNA damage. To investigate possible mechanisms, we examined the expression of p19(ARF) mRNA by RT-PCR. Cells expressing mutant K-ras produced elevated levels of p19(ARF) mRNA, which could link K-ras status with p53 expression and hence susceptibility to DNA damage-induced apoptosis.

Animals↗
PubMed2001

The impact of a 10-year audit cycle on blood usage in a district general hospital.

As clinical governance moves from concept to practice, it is emerging as a realistic strategy to promote and improve quality within the National Health Service, as well as satisfying the demand for external accountability. In the context of blood transfusion, the area of responsibility encompasses product liability, as well as efficient use of blood as a resource and transfusion as an appropriate clinical response. Clinical governance may be a modern catch phrase, but the principles it enshrines have long been established within blood transfusion, and in other aspects of haematology. Here, an audit cycle comprising four audits over a 10-year period to monitor the use of cross-matched blood in a large district general hospital is described. Initially, blood use was considered by hospital site, and by the surgical procedure for which it was requested. Later, the scope of the audit was expanded to consider usage by individual consultant. A standard of efficient use of cross-matched blood was taken to be a cross-match to transfusion ratio of < 1.5. The information was reviewed by the hospital transfusion committee, who have a key role in co-ordinating and assessing the practice of transfusion within a hospital. In this hospital, audit has been one of the main tools for improving practice, in particular by enabling the implementation and continuous revision of a maximum blood order schedule. Further, as the process of audit has developed, problem areas have been highlighted, and strategies to improve usage have been brought in with encouraging results. The audit is now being expanded again to include a greater focus on usage of cross-matched blood in the nonsurgical setting.

Blood Loss, Surgical↗
PubMed2000

Multiple copies of beta-lactoglobulin promoter do not function as LCR.

Increasing the number of transcription factor binding sites within a construct can enhance expression. In an attempt to create a synthetic locus control region for mammary expression, we have generated beta-lactoglobulin-reporter constructs with multiple copies of the cluster of transcription sites normally located within the proximal promoter. These constructs were functionally tested by stable transfection of mammary epithelial cells in vitro and in transgenic mice in vivo. Rather than enhancing expression, multimerisation of the promoter region acted neither in vivo nor in vitro to enhance expression. Indeed, its presence reduced expression. This failure to enhance expression was reflected in the inability of this region to form a DNaseI hypersensitive site autonomously in mammary chromatin in vivo. It is implicit from our study that not all combinations of transcription factor binding sites will enhance transcription.

Animals↗
PubMed1995

Restricted distribution of tetraploid cells in mouse tetraploid<==>diploid chimaeras.

Tetraploid mouse embryos were produced by electrofusion at the 2-cell stage, cultured overnight, and aggregated with normal diploid embryos to produce tetraploid<==>diploid (4n<==>2n) chimaeric conceptuses. At 7 1/2 days the 4n<==>2n chimaeras were usually smaller and developmentally retarded compared to control diploid<==>diploid chimaeras. At 12 1/2 days the 4n<==>2n chimaeras had heavier placentas but there was no significant difference in fetal size. Tetraploid cells showed a restricted tissue distribution at both developmental stages studied: 4n cells were commonly present in both the primitive endoderm and the trophectoderm lineages but they rarely contributed to the primitive ectoderm lineage. The overall similarity in the distribution of tetraploid cells at 7 1/2 and 12 1/2 days implies that whatever causes the restricted tissue distribution operates largely before 7 1/2 days. There was no evidence for excessive embryonic losses of 4n<==>2n chimaeras. So, if the restricted distribution of 4n cells was a result of cell selection, the mechanism is more likely to involve loss of 4n cells from the primitive ectoderm early in development rather than selective death of conceptuses with tetraploid cells in this lineage. Alternatively, 4n cells may be preferentially allocated to the trophectoderm and primitive endoderm rather than the primitive ectoderm layer at the blastocyst stage.

Animals↗
PubMed1994

A chimaeric animal model for confined placental mosaicism.

The reason for chromosome mosaicism being sometimes confined to only part of the conceptus is unknown. To address this problem, we produced tetraploid<-->diploid chimaeric mouse conceptuses. At 12 1/2 days, no tetraploid cells were detected in the fetus. They rarely contributed to other derivatives of the primitive ectoderm lineage but were commonly found in the primitive endoderm and trophectoderm lineages. This provides a useful animal model of human confined placental mosaicism and suggests that the primitive endoderm (hypoblast) lineage should be included in future studies of human mosaic conceptuses.

Aneuploidy↗
PubMed1994

A developmental teaching method applied to a select group of nursing students.

This study investigates the relationships between Integrated Skills Reinforcement (ISR), an instructional method that reinforces basic skills, student reading comprehension and student attrition rates using a quasi-experimental method. Ninety-three junior level baccalaureate nursing students at a city university participated in the study. One class of 42 students taught by the ISR method was designated the treatment group. Another class of 51 students taught by the lecture method served as the comparison group. Reading comprehension data were collected by retest and posttest the second and twelfth weeks of the semester, respectively, using the Descriptive Test of Language Skills (DTLS). Differences between the comparison and treatment group mean scores on the DTLS were not statistically significant (p < .05), however, both groups evidenced a trend toward improvement. These findings indicate that both the traditional lecture method and the ISR method effectively improve reading comprehension levels. Comparison group experienced attrition at 22.5 percent (13 students). By contrast, all 42 students in the treatment group completed the course. Possibly, some elements of the ISR method viably reduce attrition in the school of nursing at this city university.

Education, Nursing, Baccalaureate↗
PubMed1992

Electrofusion of mouse embryos results in uniform tetraploidy and not tetraploid/diploid mosaicism.

Some previous attempts to produce tetraploids experimentally have resulted in a proportion of treated embryos becoming 2n/4n mosaics at a frequency which may be as high as 20%, when using cytochalasin B as a fusigenic stimulus and cytogenetic techniques to identify putative tetraploid embryos. To investigate the possible occurrence of 4n/2n mosaicism, tetraploid embryos were produced by electrofusion, a process which allows adjacent blastomeres at the 2-cell stage to fuse following exposure to electric field pulses. Embryos used for electrofusion were hemizygous for a transgene consisting of approximately 1000 copies of the mouse beta-globin gene. After in situ hybridization, one hybridization signal is expected per diploid genome. Tetraploid cells in 7.5-, 8.5-, 9.5- and 10.5-day-old conceptuses were distinguished from diploid cells by performing in situ hybridization on histological sections. The frequency of nuclei with two hybridization signals in the 'hemizygous' tetraploid embryos was compared to diploid embryos which were either hemizygous or homozygous for the beta-globin transgene. Comparison of the frequency of nuclei with two hybridization signals between tissues of 'hemizygous' tetraploid conceptuses and homozygous diploid conceptuses showed no significant difference, which implies that the tissues in the tetraploid conceptuses were uniformly tetraploid. No evidence was found to suggest that electrofusion results in 2n/4n mosaicism.

Animals↗
PubMed1978

A computerized scheme for the preparation of parenteral nutrition regimes.

An operational computerized system to aid clinicians in the design of total parenteral nutrition regimes is reported. Two computer programs are described. The 'Requirements' program uses patient data and the results of blood and fluid excretion analyses to calculate the nutritional requirements for a period of 24 hours. Accepted formulae are used in these calculations. The 'Bottle Selection' program fits an intravenous bottle regime to the patient requirements from a standard set of commercially available intravenous feeding solutions. The system has been well accepted by the clinical staff who are free to accept, modify or reject a regime. Financial savings have been noted by the pharmacy who can plan for a faster turnover of a smaller range of solutions. The programs have been used routinely on a programmable calculator and have been written in CORAL for a Ferranti Argus 700E computer.

Blood Chemical Analysis↗
PubMed1976

An off-line data processing system for biochemistry profiling based on a 2K programmable calculator.

An off-line data processing system based on a Hewlett Packard 2K programmable calculator to be used with a biochemistry profiling system is described. The program is in two sections. A Data Acquisition phase calculates results from Auto Analyser II peak heights after corrections for drift and stores them on magnetic tape cassettes. Quality control statistics are produced. A Reporting phase types the profile results on self-adhesive pre-printed labels to be attached to the test-request form and also prepares a laboratory record sheet. The system is routinely used to process up to 2000 peak heights per day. Non-profile heights may also be read using this program.

Autoanalysis↗
PubMed1971

Rat gastric acid secretion studies with histamine and synthetic gastrin-like pentapeptide.

1. Gastric acid secretion was measured in the urethane anaesthetized rat whilst maintaining a recirculated gastric perfusion fluid at pH 4.2. The latent period of onset of secretion following single intravenous doses of histamine and pentapeptide in combination was significantly shorter than that following either stimulant alone.3. When administered over a period of 2 hr the maximal steady rate of secretion in response to pentapeptide was 75% of that to histamine.4. Acid stimulatory effects were additive both when the drugs were given concurrently over a 2 hr period and when one was administered after a maximal response had been obtained to the other.5. Although there is some evidence to indicate that histamine and pentapeptide might be initiating acid secretion by different mechanisms it is suggested that they may not be acting with total independence.

Animals↗
PubMed1968

Influence of intragastric pH on electrolyte secretion by the guinea-pig stomach.

1. A technique is described for the continuous assessment of acid secretion by the guinea-pig gastric mucosa at selected levels of intragastric pH.2. The rate of hydrogen ion secretion increases linearly with pH over the intragastric range of pH 4.4 to 9.4. Sodium and potassium secretions are not clearly related to pH. Outputs of both chloride and bicarbonate rise as pH is increased.3. The carbonic anhydrase inhibitor acetazolamide reversibly reduces rapid rates of acid secretion as occur when gastric contents are maintained at pH 10.4. Alkali stimulated acid output is not inhibited by atropine (2 mg/kg) and probably results directly from increased carbonic anhydrase activity as the in vitro activity of the enzyme may be correlated with the rate of acid secretion over a wide range of pH.

Acetazolamide↗