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Biomedical subjects

G James

Publications and source records attributed to G James.

At least 37 records · Page 2Linked to original sources

Luminescence control in the marine bacterium Vibrio fischeri: An analysis of the dynamics of lux regulation.

A mathematical model has been developed based on the fundamental properties of the control system formed by the lux genes and their products in Vibrio fischeri. The model clearly demonstrates how the components of this system work together to create two, stable metabolic states corresponding to the expression of the luminescent and non-luminescent phenotypes. It is demonstrated how the cell can "switch" between these steady states due to changes in parameters describing metabolic processes and the extracellular concentration of the signal molecule N-3-oxohexanoyl-l-homoserine lactone. In addition, it is shown how these parameters influence how sensitive the switch mechanism is to cellular LuxR and N-3-oxohexanoyl-l-homoserine lactone and complex concentration. While these properties could lead to the collective phenomenon known as quorum sensing, the model also predicts that under certain metabolic circumstances, basal expression of the lux genes could cause a cell to luminesce in the absence of extracellular signal molecule. Finally, the model developed in this study provides a basis for analysing the impact of other levels of control upon lux regulation.

4-Butyrolactone↗

Intraventricular haemorrhage due to ruptured posterior inferior cerebellar artery aneurysm in tuberculous meningitis.

A 9-year-old Asian boy with known miliary tuberculosis, tuberculous meningitis and hydrocephalus was successfully treated with chemotherapy and ventriculoperitoneal shunting, but re-presented 7 months later with an intraventricular haemorrhage secondary to a ruptured left posterior inferior cerebellar artery mycotic aneurysm. The aneurysm was successfully treated by craniotomy and clipping. Tuberculous mycotic intracranial aneurysms are rare, but they should be considered in patients with tuberculous meningitis, particularly when there is a rapid neurological deterioration which may represent rupture.

Aneurysm, Infected↗

Effects of two intermittent alendronate regimens in the prevention or treatment of postmenopausal osteoporosis.

In clinical practice, a large proportion of patients have bone mass values for which a therapeutic intervention is considered necessary, but the accepted aim might be the sole preservation or marginal increases of the actual bone mass. These goals might be achieved with lower or intermittent doses of a powerful agent for the purpose of fewer side effects and improved compliance. The aim of this study was to assess the effects of two intermittent alendronate regimens in the treatment of postmenopausal osteoporosis. One hundred twenty-four postmenopausal women (age range 52-75 years, at least 7 years since last menopause) with a bone mineral density (BMD) at either the femoral neck or lumbar spine of 2 SD below the mean values of young healthy individuals, and without a history of previous osteoporotic fracture, were randomly assigned either to calcium/vitamin D supplements, alone or associated with two different intermittent oral alendronate regimens: 20 mg once a week (weekly alendronate group) or 10 mg daily (orally) for 1 month out of 3 (cyclical alendronate group). After 1 year, in both groups given intermittent alendronate, we observed significant increases in BMD at both the spine (+2.2 +/- 2.6 and +2.5 +/- 2.9) and femoral neck (+1.6 +/- 4.8 and +1.5 +/- 2.2) for the weekly and cyclical regimens, respectively. This was associated with a significant diminution of both serum bone-specific alkaline phosphatase and urinary N-telopeptides of collagen type I excretion. In the patients in the control group BMD decreased significantly at the lumbar spine, with a slight decline of serum bone-specific alkaline phosphatase. Compliance with treatment and drug tolerability were good in both alendronate groups. In conclusion, intermittent alendronate administration at cumulative doses (and costs) three times lower than those currently recommended for osteoporosis treatment is very well accepted, and is able to significantly increase BMD at the spine and femoral neck and to decrease the markers of bone turnover. These regimens can be clinically useful in the long-term treatment of postmenopausal osteoporosis without prevalent osteoporotic fractures, particularly in women with lower compliance for continuous administration.

Administration, Oral↗

Sources and impact of artifacts on clinical three-dimensional ultrasound imaging.

The purpose of this paper is to investigate, identify and discuss artifacts and their sources arising in three-dimensional ultrasound (3D US) in clinical practice in order to increase the awareness of clinicians and sonographers with respect to common 3D US artifacts and to use this increased awareness to avoid or reduce the occurrence of misdiagnosis in 3D US studies. Patient 3D US data were acquired using several different scanners and reviewed interactively on the scanner and graphics workstations. Artifacts were catalogued according to artifact origin. Two-dimensional ultrasound (2D US) artifacts were classified whether they were of a B-mode or color/power Doppler origin and their presentation in the original scan planes and the resulting volume re-sliced planes and rendered images was identified. Artifacts unique to 3D US were observed, noted and catalogued on the basis of whether they arose during acquisition, rendering or volume editing operations. Acoustic artifacts identified included drop-out, shadowing, etc. whose presentation depended on the relationship between slice and imaging plane orientation. Color/power Doppler artifacts were related to gain, aliasing, and flash which could add apparent structure or confusion to the volume images. Rendered images also demonstrated artifacts due to shadowing and motion of adjacent structures, cardiac motion or pulsatility of the cardiac septum or vessel walls. Editing artifacts potentially removed important structures. Three-dimensional ultrasound is prone to the same types of artifacts encountered in 2D US imaging plus others unique to volume acquisition and visualization. The consequences of these diagnostically significant artifacts include mimicking of abnormal development, masses, or missing structures thus requiring careful study before reaching a diagnosis.

Artifacts↗

Artifacts and the visualization of fetal distal extremities using three-dimensional ultrasound.

OBJECTIVES: To demonstrate that acoustic shadowing in 3D US may give rise to artifacts simulating limb defects and provide a solution to eliminate its occurrence. METHODS: Twenty second trimester fetuses (gestational age 15-24 weeks) were scanned with three-dimensional ultrasound (3D US) using a sagittal acquisition plane. Fetal tibia/fibula and radius/ulna pairs were assessed for completeness of imaging. A further 20 fetuses (gestational age 20-26 weeks) were scanned in both axial and sagittal planes and the results compared to verify clear visualization of both bones. RESULTS: Shadowing from adjacent structures produced an apparent limb defect in 55% of the first 20 fetuses imaged only sagittally (18% of limb pairs). Acquiring data from more than one orientation avoided this artifact. CONCLUSIONS: The 3D US is subject to the same artifacts as two-dimensional (2D US) in terms of acoustic shadowing, although their presentation may be different. Awareness of this fact is essential for correct interpretation of 3D US studies. Three-dimensional scanning protocols should be modified to ensure that fetal structures are adequately visualized by acquiring volume data in more than one acquisition orientation.

Artifacts↗

Molecular genotyping of human Ureaplasma species based on multiple-banded antigen (MBA) gene sequences.

Ureaplasma urealyticum has been divided into 14 serovars. Recently, subdivision of U. urealyticum into two species has been proposed: U. parvum (previously U. urealyticum parvo biovar), comprising four serovars (1, 3, 6, 14) and U. urealyticum (previously U. urealyticum T-960 biovar), 10 serovars (2, 4, 5, 7-13). The multiple-banded antigen (MBA) genes of these species contain both species and serovar/subtype specific sequences. Based on whole sequences of the 5'-ends of MBA genes of U. parvum serovars and partial sequences of the 5'-ends of MBA genes of U. urealyticum serovars, we previously divided each of these species into three MBA genotypes. To further elucidate the relationships between serovars, we sequenced the whole 5'-ends of MBA genes of all 10 U. urealyticum serovars and partial repetitive regions of these genes from all serovars of U. parvum and U. urealyticum. For the first time, all four serovars of U. parvum were clearly differentiated from each other. In addition, the 10 serovars of U. urealyticum were divided into five MBA genotypes, as follows: MBA genotype A comprises serovars 2, 5, 8; MBA genotype B, serovar 10 only; MBA genotype C, serovars 4, 12, 13; MBA genotype D, serovar 9 only; and MBA genotype E comprises serovars 7 and 11. There were no sequence differences between members within each MBA genotype. Further work is required to identify other genes or other regions of the MBA genes that may be used to differentiate U. urealyticum serovars within MBA genotypes A, C and E. A better understanding of the molecular basis of serotype differentiation will help to improve subtyping methods for use in studies of the pathogenesis and epidemiology of these organisms.

Amino Acid Sequence↗

Survival analysis in percutaneous endoscopic gastrostomy feeding: a worse outcome in patients with dementia.

OBJECTIVE: Percutaneous endoscopic gastrostomy (PEG) feeding has been validated in specific clinical situations such as acute stroke with dysphagia and oropharyngeal malignancy. The perception that gastrostomy insertion is safe and technically simple has led to an increase in the demands for PEG insertion, encompassing clinical applications such as in patients with dementia, in whom its role has not been justified. The purpose of this study was to compare the mortality of patients with dementia who were fed by PEG to that of other subgroups of patients requiring gastrostomy feeding. METHODS: The study focused on a cohort of 361 consecutive patients requiring PEG feeding between August 1992 and July 1997 from two District General Hospitals (Rotherham District General Hospital and Doncaster Royal Infirmary) in South Yorkshire. A retrospective cohort survival analysis was performed using the Kaplan-Meier survival method and Cox proportional hazards analysis. RESULTS: In all patients requiring gastrostomy feeding there is a high initial mortality of 28% at 30 days. However, patients with dementia have a worse prognosis compared to other subgroups, with 54% having died at 1 month and 90% at 1 yr (log rank test p < 0.0001). This difference remained significant (log rank p < 0.0001) after adjusting for age at the time of PEG insertion. CONCLUSIONS: This is the first demonstration in the United Kingdom that the mortality of patients with dementia who are fed by gastrostomy is considerable. Consequently, we may wish to advise against gastrostomy feeding in selected patients within this clinical setting.

Aged↗

Mycobacterium genavense infection in two aged ferrets with conjunctival lesions.

Mycobacterium genavense infection was diagnosed in two adult ferrets. Disseminated mycobacteriosis was diagnosed in a castrated 5-year-old sable ferret with generalised peripheral lymph node enlargement and a proliferative lesion of the conjunctiva of the nictitating membrane. The diagnosis was based on characteristic cytology and sequence analysis of the 16S rRNA gene amplified using the polymerase chain reaction from fresh biopsy material. Therapy with rifampicin, clofazimine and clarithromycin probably cured the infection. An entire 4-year-old female ferret with conjunctival swelling, serous ocular discharge and swelling of the subcutaneous tissues of the nasal bridge was diagnosed as having M genavense infection on the basis of typical cytology, histopathology and sequence analysis of 16S rRNA amplicons from formalin-fixed paraffin-embedded tissue. This patient was treated successfully using rifampicin. Both ferrets subsequently died as a result of other disease conditions, 10 and 4 months following initiation of therapy, respectively. This is the first report documenting M genavense as a cause of disseminated mycobacterial disease in ferrets. Conjunctival involvement may be a feature of disseminated mycobacteriosis in the ferret. The possibility that these infections were the consequence of a ferret retrovirus infection should be considered further.

Animals↗

Species identification and subtyping of Ureaplasma parvum and Ureaplasma urealyticum using PCR-based assays.

There is good evidence that the organism currently known as Ureaplasma urealyticum should be divided into two species-U. parvum (previously U. urealyticum biovar 1) and U. urealyticum (previously U. urealyticum biovar 2). In this study, we designed a series of primers, targeting the 16S rRNA gene and 16S rRNA-23S rRNA intergenic spacer regions, the urease gene subunits, and the 5' ends of the multiple-banded antigen (MBA) genes, to identify and subtype these Ureaplasma species. All of the species-specific primer pairs could distinguish the two species, but only subtype-specific primer pairs targeting the MBA genes could distinguish subtypes within each species. U. parvum was separated into three subtypes, represented by serovars 1, 3/14, and 6. U. urealyticum was also separated into three subtypes by PCR and/or direct sequencing. Subtype 1 consisted of serovars 2, 5, 8, and 9; subtype 2 contained serovars 4, 10, 12, and 13; and subtype 3 contained serovars 7 and 11. A selection of primer pairs was used to identify and subtype 78 clinical ureaplasma isolates from vaginal swabs of pregnant women and to identify and subtype ureaplasmas directly in 185 vaginal swabs in which they had been previously detected. U. parvum was identified in 228 (87%) of 263 isolates or specimens, and U. urealyticum was identified in 50 (19%) (both were present in 6%). Serovars 3/14 (48%) and 1 (43%) were most common among U. parvum isolates, and subtypes 2 (62%) and 1 (34%) were most common among U. urealyticum isolates. This new PCR-based typing system will facilitate future studies of the relationship between individual Ureaplasma species or subtypes and human disease.

Antigens, Bacterial↗

Identification by 16S rRNA gene analyses of a potential novel mycobacterial species as an etiological agent of canine leproid granuloma syndrome.

PCR amplifications of the 16S rRNA gene were performed on 46 specimens obtained from 43 dogs with canine leproid granuloma syndrome to help determine its etiology. Sequence capture PCR was applied to 37 paraffin-embedded specimens from 37 dogs, and nested PCR was attempted on DNA from 9 fresh tissue specimens derived from 3 of the 37 aforementioned dogs and from an additional 6 dogs. Molecular analyses of the paraffin-embedded tissues and fresh tissue specimen analyses were performed at separate institutions. PCR products with identical sequences over a 350-bp region encompassing variable regions 2 and 3 of the 16S rRNA gene were obtained from 4 of 37 paraffin-embedded specimens and from all 9 specimens of fresh tissue originating from 12 of the 43 dogs. Identical sequences were determined from amplicons obtained from paraffin-embedded and fresh specimens from one dog. The consensus DNA sequence, amplified from paraffin-embedded tissue and represented by GenBank accession no. AF144747, shared highest nucleotide identity (99.4% over 519 bp) with mycobacterial strain IWGMT 90413 but did not correspond exactly to any EMBL or GenBank database sequence. With a probe derived from the V2 region of the novel canine sequence, reverse cross blot hybridization identified an additional four paraffin-embedded specimens containing the same novel sequence. In total, molecular methodologies identified the proposed novel mycobacterial sequence in 16 of 43 dogs with canine leproid granuloma syndrome, indicating that the species represented by this sequence may be the principal etiological agent of canine leproid granuloma syndrome.

Animals↗

Adenosine 5' triphosphate evoked mobilization of intracellular calcium in central nervous system white matter of adult mouse optic nerve.

Although it has been established that immature glial cells express functional purinergic receptors, the responsiveness of mature glial cells in vivo had not been elucidated. This question was addressed using fura-2 ratiometric measurements of [Ca2+]i in the adult mouse optic nerve, a central nervous system (CNS) white matter tract, taking advantage of the facts that (i), the optic nerve contains glial cells but not neurons and (ii), that fura-2 loads primarily astrocytes in isolated intact optic nerves. We show that adenosine 5' triphosphate (ATP) evoked an increase in [Ca2+]i in a concentration-dependent manner with a half-maximal effect at 3 microm ATP, and with a rank order of agonist potency of ATP > ADP > alpha,beta-methyline-ATP > UDP > adenosine. The results indicate mainly P2Y and P2X components, consistent with the in vitro astroglial purinergic receptor profile. The in vivo response of mature glia to ATP may be important in their response to CNS damage.

Adenosine Triphosphate↗

Phylogenetic analysis of Ureaplasma urealyticum--support for the establishment of a new species, Ureaplasma parvum.

In this study, the phylogenetic relationships between the two biovars and 14 serovars of Ureaplasma urealyticum were studied using the sequences of four different genes or genetic regions, namely: 16S rRNA genes; 16S-23S rRNA gene spacer regions; urease gene subunits ureA, ureB, partial ureC and adjoining regions upstream of ureA, ureA-ureB spacer and ureB-ureC spacer; the 5'-ends of the multiple-banded antigen (MBA) genes. U. urealyticum genotypes, based on all four genomic sequences, could be clearly separated into two clusters corresponding with currently recognized biovars 1 and 2. Sequences were generally conserved within each biovar. However, there was heterogeneity within the 5'-end regions of the MBA genes of the four serovars of biovar 1; the sequence of serovar 3 was identical with the previously published sequence and differed by only three bases from that of serovar 14; but there were significant differences between the sequences of serovars 3 and 14 and those of serovars 1 and 6. Based on the phylogenetic analysis, support is given to previous recommendations that the two biovars of U. urealyticum be classified as distinct species, namely U. parvum and U. urealyticum for biovars 1 and 2, respectively. In the future, the relationship between the new species and clinical manifestations of ureaplasma infections should be studied.

5' Untranslated Regions↗

Osteochondrodysplasia in Scottish Fold cats.

OBJECTIVE: To better characterise the bone and joint problems which can develop in Scottish Fold cats. DESIGN: Retrospective study of cases seen in five veterinary clinics and radiographic survey of cats in a cattery. RESULTS: Six Scottish Fold cats (four castrated males, two spayed females) aged between 5 months and 6 years were presented for signs of skeletal disease including lameness, reluctance to jump, a stiff stilted gait, short misshapen distal limbs, swelling of plantar tarsometatarsal regions and short thick inflexible tails. A further four cases (one male, three females, 15 months to 11 years) were identified by radiographic screening of a cattery. A diagnosis of osteochondrodysplasia was based on characteristic radiological findings including irregularity in the size and shape of tarsal, carpal, metatarsal and metacarpal bones, phalanges and caudal vertebrae, narrowed joint spaces, and progressive new bone formation around joints of distal limbs with diffuse osteopenia of adjacent bone. A plantar exostosis caudal to the calcaneus was present in advanced cases. In all nine cases where pedigree information was available, affected cats allegedly originated from the mating of a Scottish Fold to a cat with normal ears. The severity and time of onset of physical signs, and rate of progression and extent of radiographic abnormalities, varied from case to case. Limited histological observations suggested the underlying problem may be an osteochondrodysplasia, related to inadequate cartilage maturation. Clinical signs were ameliorated by administration of pentosan subcutaneously in two of three cats in which it was trailed, and one of these also benefited from an oral glycosaminoglycan preparation. CONCLUSIONS: Clinical and radiological findings were ascribed to defective maturation and function of cartilage, particularly in the distal limbs, ears and tail. As all Scottish Fold cats suffered from osteochondrodysplasia of some degree, the best solution would be to avoid using fold-eared cats for breeding and instead use Scottish shorthairs.

Animals↗

Role of an improvement in acid-base status and nutrition in CAPD patients.

Short-term correction of metabolic acidosis in normal and uremic subjects has been shown to decrease protein degradation, but the long-term effects of better correction of acidosis on nutrition in ESRF are unknown. The aim of this study was to assess the possible benefits, in the nutritional state and morbidity, of improved correction of acidosis in the first year of treatment with continuous ambulatory peritoneal dialysis (CAPD). Two hundred consecutive new CAPD patients were randomized, in a single-blind fashion, to receive a high (HA; lactate 40 mmol/liter) or low (LA; lactate 35 mmol/liter) alkali dialysate for one year. Calcium carbonate and sodium bicarbonate were also used to correct acidosis in the HA group. At one year, the venous serum bicarbonate and arterial pH were 7.44 +/- 0.004 and 27.2 +/- 0.3 mmol/liter in the HA group, and 23.0 +/- 0.3 mmol/liter and 7.4 +/- 0.004 in the LA group (P < 0.001). Dialysis dose, at one year or at the point of leaving the study (HA 8.0 +/- 0.1 liters/day vs. LA 8.5 +/- 0.3 liters/day) was not significantly different (P = 0.18). At one year, the increase in body weight in the HA group (6.1 +/- 0.66 kg) was higher than in the LA group (3.71 +/- 0.56 kg, P < 0.05). The increase in midarm circumference in the HA patients (1.26 +/- 0.16 cm) was significantly higher than the increase in the LA patients (0.61 +/- 0.16 cm, P < 0.05). The increase in triceps skinfold thickness were not significantly different (HA 2.5 +/- 0.41 mm vs. LA 1.24 +/- 0.38 mm, P = 0.1). Serum albumin was 37.8 +/- 0.4 g/dl at one year in the HA group, and 38.2 +/- 0.5 g/dl in the LA group (NS). Dietary protein intake at one year (HA 0.9 +/- 0.2 g/kg/day vs. LA 1.0 +/- 0.1 g/kg/day) was not significantly different. There were fewer hospital admissions in the HA group (1.13 +/- 0.16 per patient per year) compared to the LA group (1.71 +/- 0.22 per patient per year, P < 0.05). The HA patients spent less days in hospital per year than the LA patients (16.4 +/- 1.4 days/year vs. 21.2 +/- 1.9 days/year; P < 0.05). It is concluded that better correction of metabolic acidosis leads to greater increases in body weight and midarm circumference, but not triceps skinfold thickness, in the first year of CAPD. The improvement in morbidity, in terms of number of admissions and days in hospital per year, may be associated with the improvement in nutritional state.

Acid-Base Equilibrium↗

Using the Youth Risk Behavior Survey to compare risk behaviors of Texas High School and college students.

This study used the Youth Risk Behavior Survey (YRBS) to assess selected health behaviors of Texas high school and college students. The YRBS was administered during 1993 in paper and pencil form to 6,015 high school students representing 329 classrooms from 78 school districts. A total of 1,408 college students representing 23 college and universities were surveyed by telephone in 1993 using a modified version of YRBS. Texas college students reported a higher percentage who had experienced sexual intercourse (82% versus 55.4%), but Texas high school students reported a younger age of first sexual intercourse. High school students also initiated alcohol consumption at a younger age, although college students were more likely to binge drink (33.5% versus 31%). Regular cigarette use also was higher among college students (25.4% versus 19.3%), but was initiated at a younger age by high school students. Study results indicate that health education programs must begin much earlier than during the high school years. Due to early initiation of negative health behaviors, emphasis must be placed on abstinence and risk-reduction techniques for both populations.

Adolescent↗

Resistance of K-RasBV12 proteins to farnesyltransferase inhibitors in Rat1 cells.

Benzodiazepine (BZA)-5B, a CAAX farnesyl-transferase inhibitor, was previously shown to block the farnesylation of H-Ras and to reverse the transformed morphology of Rat1 cells expressing oncogenic H-RasV12. Non-transformed Rat1 cells were not affected by BZA-5B, suggesting that they produce a form of Ras whose prenylation is not blocked by this compound. The likely candidate is K-RasB, which differs from H-Ras primarily in the terminal 24 amino acids. In the current study we examined the effect of BZA-5B on the prenylation of a chimeric oncogenic Ras protein designated H/K-RasBV12, consisting of the first 164 amino acids of H-RasV12 followed by the last 24 amino acids of K-RasB. BZA-5B failed to block the prenylation of this chimera and was thus unable to reverse the transformed morphology of Rat1 cells in which it was expressed. Another potent inhibitor of H-Ras farnesylation, L-739,749, also failed to block prenylation of H/K-RasBV12. Similar results were obtained in transfected cells expressing a widely used version of K-RasBV12 containing a 10-amino acid extension at its NH2 terminus. Neither BZA-5B nor L-739,749 reversed the transformed morphology of cells expressing H/K-RasBV12. The resistance of K-RasB to farnesyltransferase inhibition provides a likely explanation for the resistance of nontransformed cells to the growth inhibitory effects of BZA-5B and L-739,749.

Alkyl and Aryl Transferases↗