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Biomedical subjects

T Roberts

Publications and source records attributed to T Roberts.

At least 37 records · Page 2Linked to original sources
PubMed1999

TTC4, a novel human gene containing the tetratricopeptide repeat and mapping to the region of chromosome 1p31 that is frequently deleted in sporadic breast cancer.

The 1p31 region shows loss of heterozygosity in up to 50% of human breast cancers, indicating the presence of a tumor suppressor gene in this location. We have mapped six novel ESTs to a 15-Mb contig of yeast artificial chromosomes spanning the critical region of 1p31. One of these ESTs was localized within the contig to the region most commonly undergoing loss of heterozygosity in breast cancer. The corresponding gene sequence for this EST was established by cDNA cloning and RACE procedures. This gene is 2 kb long and contains a tetratricopeptide repeat motif and a coiled-coil domain. This family of genes has been implicated in a wide variety of functions, including tumorigenesis. This is the fourth member of the human gene family, and so we have named this gene TTC4. Northern blot analysis demonstrates a ubiquitous pattern of gene expression that includes breast tissue. A preliminary screen of human breast cancer cell lines shows that TTC4 is expressed in all cases, but SSCP analysis of the coding region of this gene following RT-PCR failed to reveal any mutations. Clearly, because of its map location, a more extensive analysis is warranted to establish whether subtle mutations are present in breast cancers.

Amino Acid Sequence↗
PubMed1999

[Diagnosis of an intramyocardial hematoma via MRI after a traumatic myocardial infarct].

Traumatic cardiac lesions occur in about 30% of all traumatized patients, in most cases they are due to traffic accidents. We report a patient who suffered from a traumatic anterior wall infarction following a ski accident. Consecutively, an extended intramyocardial hemorrhage occurred. A left ventricular pseudoaneurysm was considered first by echocardiography. Using MRI, an intramyocaridal hemorrhage could be diagnosed because of a thin myocardial border surrounding the hematoma. Consecutively, the patient underwent CABG surgery as well as a resection of the intramyocardial hematoma. This diagnosis could be manifested surgically and histologically.

Aged↗
PubMed1999

Diurnal variation in saliva estriol level during pregnancy: a pilot study.

OBJECTIVE: The object of the study was to characterize daily values and patterns of salivary estriol levels during normal pregnancy at mid to late gestation. STUDY DESIGN: We measured salivary estriol levels in a clinical research center setting with an established enzyme-linked immunosorbent assay. Fourteen pregnant women (24-36 weeks' gestation) submitted unstimulated saliva samples hourly from 10:00 am until 10:00 pm and at midnight and 2:00, 4:00, 6:00, and 8:00 am. RESULTS: Each subject demonstrated greater salivary estriol levels at night (10:00 pm-6:00 am) than in the daytime (8:00 am-9:00 pm, P <.001). Salivary estriol levels consistently increased at 10:00 pm, peaked at 4:00 am, and returned to daytime levels between 6:00 and 7:00 am. Salivary estriol concentrations were stable during daylight hours. CONCLUSIONS: (1) There was a dramatic diurnal variation in salivary estriol levels (nadir during daylight with nighttime apogee). (2) Diurnal patterns and salivary estriol levels were consistent in each of 14 subjects evaluated in the latter half of pregnancy. Samples for baseline measurements of salivary estriol level should be obtained during daylight hours (8:00 am-8:00 pm).

Adolescent↗
PubMed1999

Successful treatment of cerebral toxoplasmosis in a marrow transplant recipient: contribution of a PCR test in diagnosis and early detection.

We report successful treatment of cerebral toxoplasmosis in an unrelated donor marrow transplant recipient. The clinical diagnosis was confirmed by polymerase chain reaction (PCR) amplification for T. gondii-DNA performed both on cerebrospinal fluid and blood leukocytes. Retrospective testing of stored blood samples demonstrated positive leukocyte PCR signal detected up to 52 days prior to onset of clinical symptoms. This case highlights the value of PCR in the diagnosis and early detection of cerebral toxoplasmosis.

Adult↗
PubMed1999

'Hello, my name is Gabriel, I am the house officer, may I examine you?' or the Objective Santa Christmas Examination (OSCE).

OBJECTIVE: To design a clinical examination of high content validity suitable for use as a formative assessment tool with pre-registration house officers (PRHO'S) towards the end of their first house officer post. DESIGN: A multicentre collaboration between four UK medical schools who offer undergraduate curricula which are problem-based, systems-based, patient-orientated, student-centred, jargon-laden and utterly staff-bewildering. MAIN OUTCOME: An objective structured clinical examination (OSCE) which is suitable for use with graduates of UK medical schools. It assesses the knowledge, skills and attitudes essential for future careers in a hierarchical system where protecting the senior staff from all forms of irritation is paramount. RESULTS: PRHO'S who excel in this examination get better references. CONCLUSION: The OSCE format can be used to provide 'real-life' scenarios appropriate to the season.

Career Choice↗
PubMed1999

Responses of single taste fibers and whole chorda tympani and glossopharyngeal nerve in the domestic pig, Sus scrofa.

Whole nerve, as well as single fiber, responses in the chorda tympani proper (CT) and glossopharyngeal (NG) nerves of 1- to 7-week-old pigs were recorded during taste stimulation. In the CT acids and in the NG bitter compounds gave the largest responses. Both nerves exhibited large responses to monosodium glutamate (MSG), MSG with guanosine 5'-monophosphate (GMP) and MSG with inositine 5'-monophosphate (IMP) as well as to glycine, xylitol, sucrose, fructose and glucose. Alitame, aspartame, betaine, neohesperedin dihydrochalcone (NHDHC), super-aspartame, saccharin and thaumatin elicited no or little response. Hierarchical cluster analysis of 49 CT fibers separated four major clusters. The M cluster, comprising 28.5% of all fibers, is characterized by strong responses to MSG, KCl, LiCl and NaCl. The responses to NaCl and LiCl were unaffected by amiloride. The H cluster (24.5%) includes units responding principally to acids. The Q cluster (18.5%) responds to quinine hydrochloride (QHCl), sucrose octaacetate (SOA) and salts with amiloride. The S cluster (28.5%) exhibits strong responses to xylitol, glycine and the carbohydrates as well as to MSG alone and to MSG with GMP or IMP. In 31 NG fibers, hierarchical cluster analysis revealed four clusters: the M cluster (10%), responding to MSG and MSG with GMP or IMP; the H cluster (13%), responding to acids; the Q cluster (29%), responding strongly to QHCl, SOA and tilmicosinR; and the S cluster (48%), responding best to xylitol, carbohydrates and glycine but also to the umami compounds. Multidimensional scaling analysis across fiber responses to all stimuli showed the best separation between compounds with different taste qualities when information from both nerves was utilized.

Age Factors↗
PubMed1999

Carboplatin and paclitaxel, alone and in combination: dose escalation, measurement of renal function, and role of the p53 tumor suppressor gene.

In this pharmacokinetic and dose-escalation study of the carboplatin/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) combination, patients were randomly assigned to receive paclitaxel either as a 1-hour or a 3-hour infusion. The 1-hour infusion was feasible, with maximum tolerated doses similar to those previously reported for a 3-hour infusion. Using patients' age, height, plasma creatinine, and plasma creatine kinase provided an improved estimate of the glomerular filtration rate compared with the more traditional creatinine-based formulas according to population analysis of data derived from glomerular filtration rate estimates performed by an isotope method. Studies of the p53 gene sequence of ovarian tumors at diagnosis suggest that p53 mutations are a potent predictor of response to subsequent treatment with carboplatin.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Observations on centrifugation: application to centrifuge development.

This report outlines the background to the development of an automated, serial, discrete centrifuge, reporting on the criteria considered essential in such an instrument. We established the criteria by examining the detailed logistics of centrifuge operation in a hospital laboratory. The mean sample load per run, using six centrifuges, was 13.6 samples, and the user-selectable cycle time ranged from 00:01:10 to 00:12:33 (hours:minutes:seconds) with a fixed g value of 1050. During the laboratory working window, (0900-1700), only 50% of the centrifuge capacity was utilized and more than one-third of the sample workload was delayed for >5 min because the centrifuges were not emptied promptly. In addition, 35% of the sample workload was centrifuged for less than the time prescribed in the operational specifications. Based on these findings, we designed a new continuous, serial centrifuge to overcome some of the deficiencies noted in the logistics study. The centrifuge operates continuously, nominally treating 150 samples/h, with a cycle time of 5 min at 1,000 g. The cycle time and g value are variable between limits, and their selection governs the throughput rate. Each sample is centrifuged separately in individual rotors mounted in a sturdy carousel with a periphery that traverses a load/unload station. There is no sample delay because of operator absence, and the capacity is fully utilized. The centrifuge can operate in a stand-alone capacity or has the capability of being integrated into a sample preparation system or as a direct front end for high-throughput analyzers.

Centrifugation↗
PubMed1998

Behavioral and single chorda tympani taste fiber responses in the common marmoset, Callithrix jacchus jacchus.

Gustatory responses of the common marmoset were studied using single fiber recordings from chorda tympani (CT) nerve and two bottle preference (TBP) tests. Hierarchical cluster analysis of 43 fibers' response profiles revealed 3 major clusters of fibers characterized by predominant sensitivity to sweeteners (S cluster), bitter compounds (Q cluster) or acids (H cluster). NaCl as well as LiCl did not stimulate CT taste fibers. The TBP tests showed relationship between a compound's ability to stimulate the taste fibers and the animals' consumption. Activity in the S cluster was associated with preference, while the activity in the Q cluster was associated with rejection. Marmosets neither preferred nor rejected sweeteners which did not stimulate any CT fibers.

Animals↗
PubMed1998

Cytokine transgene expression and promoter usage in primary CD34+ cells using particle-mediated gene delivery.

Induction or short-term transgenic expression of specific cytokines, growth factors, or other candidate therapeutic genes in hematopoietic progenitor or stem cells is potentially applicable to gene therapy for cancer. In this study, we explored the application of a gene gun technique, as an alternative to viral vectors, for ex vivo gene transfer into and transient gene expression in highly enriched CD34+ cells derived from human umbilical cord blood. Twenty-four hours posttransfection, 32.6 to 1500 pg/l x 10(6) CD34+ cells of transient gene expression was routinely obtained for specific cytokine and reporter genes. Transgene expression at the single-cell level was revealed by X-Gal staining of lacZ cDNA-transfected CD34+ cells. Expression of four candidate therapeutic genes, namely human granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, interleukin 2, and interferon gamma, was detectable for 4 to 7 days in CD34+ cells. A human elongation factor 1alpha promoter/intron 1 transcription unit was identified as a strong cellular promoter for CD34+ cells, exhibiting strength similar to that of the commonly employed cytomegalovirus immediate-early promoter. These results suggest that the nonviral, gene gun technique offers an efficient alternative approach for transient transgenic studies of hematopoietic cells and may provide new possibilities for certain cancer gene therapy strategies using CD34+ cells.

Antigens, CD34↗
PubMed1998

DNA vaccines expressing either the GP or NP genes of Ebola virus protect mice from lethal challenge.

DNA vaccines expressing the envelope glycoprotein (GP) or nucleocapsid protein (NP) genes of Ebola virus were evaluated in adult, immunocompetent mice. The vaccines were delivered into the skin by particle bombardment of DNA-coated gold beads with the Powderject-XR gene gun. Both vaccines elicited antibody responses as measured by ELISA and elicited cytotoxic T cell responses as measured by chromium release assays. From one to four vaccinations with 0.5 microgram of the GP DNA vaccine resulted in a dose-dependent protection from Ebola virus challenge. Maximal protection (78% survival) was achieved after four vaccinations. Mice were completely protected with a priming dose of 0.5 microgram of GP DNA followed by three or four subsequent vaccinations with 1.5 micrograms of DNA. Partial protection could be observed for at least 9 months after three immunizations with 0.5 microgram of the GP DNA vaccine. Comparing the GP and NP vaccines indicated that approximately the same level of protection could be achieved with either vaccine.

Animals↗
PubMed1998

Ciao 1 is a novel WD40 protein that interacts with the tumor suppressor protein WT1.

The Wilms tumor suppressor protein, WT1, is a transcription factor capable of activating or repressing transcription of various cellular genes. The mechanisms involved in regulating the transcriptional activities of WT1 are beginning to be unraveled. It appears that physical interactions of other cellular proteins (p53 and par-4) with WT1 can modulate the function of WT1. Here, we report the identification and cloning of a novel WT1-interacting protein termed Ciao 1, a member of the WD40 family of proteins. Ciao 1 specifically interacts with WT1 both in vitro and in vivo. This interaction alters the mobility of a WT1.DNA complex in gel shift assays, and results in a decrease in transcriptional activation mediated by WT1. Ciao 1 does not inhibit binding of WT1 to its consensus nucleotide sequence and does not affect the repression activity of WT1. Thus, Ciao 1 appears to specifically modulate the transactivation activity of WT1 and may function to regulate the physiological functions of WT1 in cell growth and differentiation.

Amino Acid Sequence↗
PubMed1998

Molecular characterization of the 1p22 breakpoint region spanning the constitutional translocation breakpoint in a neuroblastoma patient with a t(1;10)(p22;q21).

To characterize the breakpoint in a neuroblastoma patient with a constitutional rearrangement we have constructed a yeast artificial chromosome (YAC) contig extending approximately 6 Mbp in the chromosome 1p22 region that spans the D1S435 and D1S236 loci. This contig has been confirmed by the coincidence of a number of markers in different overlapping YACs. For several of these YACs the overlap was demonstrated following the isolation and sequencing of end clones from which STS markers were generated. The majority of the YACs have been shown not to be chimeric either through the analysis of somatic cell hybrids or fluorescence in situ hybridization. Following the establishment of the contig we have been able to construct a physical map of the region that incorporates six STS and three newly assigned eSTS markers. The generation of this physical map has allowed the reordering of markers in the genetic linkage map for 1p. The physical order is; tel-D1S435-D1S188-D1S424-D1S236-D1D415- D1S420. With the reordering of D1S435 we have been able to join this contig with another reported previously, thereby generating a well characterized 15 Mbp YAC contig in the 1p22-31 region. The 6 Mbp contig described here spans the chromosome 1 constitutional translocation break-point seen in a patient with a t(1;10)(p22;q21) and who had a stage 4S neuroblastoma. YAC fragmentation has been used to define a 200 Kb region within this contig containing the 1p22 breakpoint. Restriction enzyme analysis demonstrates that there are three NotI sites in this region, one of which lies close to the translocation breakpoint site.

Chromosomes, Artificial, Yeast↗
PubMed1998

MRI using hyperpolarized noble gases.

The aim of this study was to review the physical basis of MRI using hyperpolarized noble gases as well as the present status of preclinical and clinical applications. Non-radioactive noble gases with a nuclear spin 1/2 (He-3, Xe-129) can be hyperpolarized by optical pumping. Polarization is transferred from circularly polarized laser light to the noble-gas atoms via alkali-metal vapors (spin exchange) or metastable atoms (metastability exchange). Hyperpolarization results in a non-equilibrium polarization five orders of magnitude higher than the Boltzmann equilibrium compensating for the several 1000 times lower density of noble gases as compared with liquid state hydrogen concentrations in tissue and allows for short imaging times. Hyperpolarization can be stored sufficiently long (3 h to 6 days) to allow for transport and application. Magnetic resonance systems require a broadband radio-frequency system - which is generally available for MR spectroscopy - and dedicated coils. The hyperpolarized gases are administered as inhalative "contrast agents" allowing for imaging of the airways and airspaces. Besides the known anesthetic effect of xenon, no adverse effects are observed in volunteers or patients. Pulse sequences are optimized to effectively use the non-renewable hyperpolarization before it decays or is destroyed, using fast low-flip-angles strategies to allow for dynamic/breath-hold imaging of highly diffusible (He) or soluble (Xe) gases with in vivo T1-times well below 1 min. Since helium is not absorbed in considerable amounts, its application is restricted to the lung. Xe-129 is also under investigation for imaging of white matter disease and functional studies of cerebral perfusion. Magnetic resonance imaging using hyperpolarized gases is emerging as a technical challenge and opportunity for the MR community. Preliminary experience suggests potential for functional imaging of pulmonary ventilation and cerebral perfusion.

Adult↗
PubMed1998

[Acute vascular perforation with shunt formation in the right ventricle after percutaneous transluminal coronary angioplasty. Magnetic resonance tomography and Doppler ultrasound detection of shunt flow].

A coronary artery perforation is a rare complication after percutaneous transluminal coronary angioplasty. The therapy will be determined by the hemodynamic failure of the left or right ventricle. A case of a coronary artery perforation with a shunt from the right coronary artery to the right ventricle after coronary angioplasty is reported. The shunt was detected by coronary angiography and confirmed by magnetic resonance imaging and doppler echocardiography.

Aged↗
PubMed1998

[Flow quantification of intracardiac shunt volumes using MR phase contrast technique in the breath holding phase].

PURPOSE: Comparison of a breath-hold, velocity-encoded, phase-difference magnetic resonance (MR) sequence for intracardiac shunt flow measurement with the invasive shunt size determination by oximetry. PATIENTS AND METHODS: 10 patients with different cardiac shunts (6 ASD/3 VSD/1 PDA) and four healthy individuals were investigated using a 1.5 Tesla Siemens Vision system. For flow measurements a breath-hold, velocity-encoded, phase-difference magnetic resonance (MR) sequence was used ('through plane', FLASH 2D-sequence, TR/TE 110/5 ms, 'velocity encoding' 250 cm/s). Mean flow (ml/R-R interval) in the ascending aorta, the pulmonary trunk, and the right and left pulmonary arteries was determined. The ratio of the mean flow in the pulmonary circulation (Qp: sum of the mean flows in the right and left pulmonary arteries) and the systemic circulation (Qs: mean flow in the proximal aorta) was compared with the Qp/Qs ratios determined by the invasive oxymetric technique. Oximetry was performed within 24 hours after MR imaging. RESULTS: In the 4 healthy individuals MR flow measurement yielded a Qp/Qs ratio of 0.96 +/- 0.15. In the 10 patients with the various shunt defects, the non-invasive shunt determination by MR gave a Qp/Qs ratio of 2.09 +/- 0.67. The percentage of the calculated shunt sizes was 47.05 +/- 17.45%. In the comparison with the results determined by the invasive oxymetric technique, the MR data showed a strong correlation of r = 0.87. CONCLUSIONS: Breath-hold, velocity-encoded, phase-difference MR-technique enables a reliable quantification of cardiac shunts within a short acquisition time.

Adult↗