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Biomedical subjects

W Taylor

Publications and source records attributed to W Taylor.

At least 55 records · Page 3Linked to original sources
PubMed1998

The position of the ZEBRA activation domain does not influence its biological activity.

Epstein-Barr virus (EBV) is a human herpesvirus which latently infects B lymphocytes. EBV encodes a unique transcriptional activator, known as ZEBRA, which can disrupt viral latency in B cells and induce lytic viral replication. Furthermore, ZEBRA has been shown to bind at the EBV origin of lytic replication, and is necessary for viral DNA replication to occur. Previously we demonstrated that heterologous activation domains can fully substitute for the ZEBRA activation domain. Here we extend those results by showing that the position of the ZEBRA activation domain or a heterologous replacement domain does not influence its ability to function in the disruption of EBV latency. In this study three novel clones were constructed in which the ZEBRA activation region was repositioned to the carboxy terminus of the protein. These mutants were used to demonstrate that the ability of ZEBRA's wild type domain to function in the complex biological process of virus activation is not compromised by altering its position within the protein.

B-Lymphocytes↗
PubMed1998

Factors affecting inverted repeat stimulation of recombination and deletion in Saccharomyces cerevisiae.

Inverted DNA repeats are an at-risk motif for genetic instability that can induce both deletions and recombination in yeast. We investigated the role of the length of inverted repeats and size of the DNA separating the repeats for deletion and recombination. Stimulation of both deletion and recombination was directly related to the size of inverted repeats and inversely related to the size of intervening spacers. A perfect palindrome, formed by two 1.0-kb URA3-inverted repeats, increased intra- and interchromosomal recombination in the adjacent region 2,400-fold and 17,000-fold, respectively. The presence of a strong origin of replication in the spacer reduced both rates of deletion and recombination. These results support a model in which the stimulation of deletion and recombination by inverted repeats is initiated by a secondary structure formed between single-stranded DNA of inverted repeats during replication.

Chromosomes, Fungal↗
PubMed1998

Prognostic value of K-ras mutations, ras oncoprotein, and c-erb B-2 oncoprotein expression in adenocarcinoma of the lung.

This trial was undertaken to determine the prognostic role of K-ras (p21), c-erb B-2 (p185) protein expression, and the presence or nonpresence of a K-ras gene mutation in patients with adenocarcinoma of the lung. This was a retrospective study of 103 patients with adeno- or large-cell carcinoma of the lung who had available paraffin-stored tumor material. The relation of several clinical variables to survival was analyzed. Immunohistochemical techniques were used to determine expression of p21 and p185. Polymerase chain reaction (PCR) and sequencing were used to determine K-ras mutation status. Tumor stage was the only nonmolecular clinical variable predictive of survival (p=0.0001). A combination of K-ras mutation and p 185 expression (p=0.0144), ras mutation and strong p21 expression (p=0.0137), and K-ras mutation and the combined expression of p21 and p185 were predictive of poor survival (p=0.0415) in univariate analysis of all patients. The sole presence of K-ras mutation was predictive of survival. Additionally, when combined with elevated p21 or p185 expression in a subset of patients with 4 or more years of follow-up, negative correlation with survival was observed.

Adenocarcinoma↗
PubMed1998

Long-term outcome of brain manganese deposition in patients on home parenteral nutrition.

Manganese intoxication has been described in children on long term parenteral nutrition presenting with liver and nervous system disorders. Cases are reported of a brother and sister on long term parenteral nutrition with hypermanganesaemia and basal ganglia manganese deposition, detected by magnetic resonance imaging (MRI), without overt neurological signs. Following reduction of manganese intake, basal ganglia manganese was monitored by repeated MRI, and neurological and developmental examinations. An MRI intensity index of the globus pallidus declined over a three year period from 0.318 and 0.385 to 0.205 and 0.134 with concomitant falls in whole blood manganese from 323 and 516 to 226 and 209 nmol/l (normal range, 73-210 nmol/l). Unlike adult experience these children developed normally without neurological signs. In conclusion, deposited manganese is removed from neural tissue over time and the prognosis is good when neurological manifestations and liver disease are absent.

Basal Ganglia↗
PubMed1998

Oral sodium bicarbonate reduces proximal renal tubular peptide catabolism, ammoniogenesis, and tubular damage in renal patients.

Oral sodium bicarbonate (NaHCO3) is widely used to treat acidosis in patients with renal failure. However, no data are available in man on the effects on proximal renal tubular protein catabolism or markers of tubular injury. We have developed methods to allow such studies, and both increased tubular catabolism of 99mTc-labelled aprotinin (Apr*), as well as tubular damage were found in association with increased ammonia (NH3) excretion in patients with nephrotic range proteinuria. We now examine the effects of reducing renal ammoniogenesis, without altering proteinuria, using oral NaHCO3 in 11 patients with mild/moderate renal impairment and proteinuria. Renal tubular catabolism of Apr* was measured before and after NaHCO3 by renal imaging (Kidney uptake, K% of dose) and urinary excretion of free 99mTcO4- (metabolism, Met% of dose/h) over 26 h. Fractional degradation (Frac) was calculated from Met/K (/h). Fresh urine was also analyzed for NH3 excretion every fortnight from 6/52 before treatment. Total urinary N-acetyl-beta-D-glucose-aminidase (NAG) and the more tubulo-specific NAG "A2" were measured. 51CrEDTA clearance and 99mTc-MAG 3 TER were also assessed. After NaHCO3 Met over 26 h was significantly reduced (from 1.3 +/- 0.2% of dose/h to 0.9 +/- 0.1% dose/hr, p < 0.005), as was Frac of Apr* (from 0.06 +/- .006/h to 0.04 +/- 0.005/hr, p < 0.003). NH3 excretion also fell significantly (from 0.9 +/- 0.2 mmol/h to 0.2 +/- 0.05 mmol/h, p < 0.007), as did both total urinary NAG (from 169 mumol/24 h, 74-642 mumol/24 h to 79 mumol/ 24 h, 37-393 mumol/24 h, p < 0.01), and the NAG 'A2' isoenzyme (from 81.5 mumol/24 h, 20-472 mumol/24 h to 35.0 mumol/24 h, 6-388 mumol/24 h, p < 0.001). Proteinuria remained unaltered, and there was no change in blood pressure nor in glomerular haemodynamics. Oral NaHCO3 may thus pro-tect the proximal renal tubule and help delay renal disease progression.

Acetylglucosaminidase↗
PubMed1997

Anomalous venous drainage in a case of non-syndromic craniosynostosis.

The authors describe the clinical and radiological findings in a case of non-syndromic craniosynostosis affecting multiple sutures, in which the intracranial venous drainage was grossly anomalous. Investigation by magnetic resonance imaging and angiography revealed that almost all of the intracranial venous blood was draining from the dural sinuses transosseoussly via enlarged emissary veins to the external jugular veins and the vertebral veins. Although present, both internal jugular veins were small. This discovery represented a contraindication for the vault expansion surgery that had been recommended as treatment for the patient's raised intracranial pressure, and it has important implications for the management of all types of craniosynostosis.

Cerebral Angiography↗
PubMed1997

A subset of gestational trophoblastic disease characterized by abnormal chromosome 8 copy number detected by fluorescence in situ hybridization.

The present paper describes the results of research conducted to ascertain whether the report by Mark et al. [1], describing the concurrence of congenital trisomy 8 mosaicism and gestational trophoblastic disease (GTD) in a 42 year-old Gravida IV, Para IV patient was an isolated event. In contrast to other cases described in the literature, the patient described in Mark et al. [1] had no additional confounding chromosomal abnormalities other than trisomy 8. To the best of our knowledge, ours was the only reported case of constitutional trisomy 8 mosaicism associated with gestational trophoblastic disease, a rare gynecological disease entity. The question arises whether there exists a subset of patients with GTD characterized by an abnormal chromosome 8 copy number. The implicit hypothesis is that an abnormal number of chromosome 8 somehow predisposes to cancer. A pilot study of 10 cases of GTD was conducted using fluorescence in situ hybridization (FISH) and a commercial chromosome 8-specific alpha-satellite probe on formalin-fixed, paraffin-embedded patient tissues. Among eight informative cases successfully completed, two cases (25%) were found to be trisomic, when a cut-off point of 10% trisomic cells is adopted. Another two cases (25%) were found to be triploid. The results of our FISH study indicated that an abnormal chromosome 8 copy number found in Mark et al. [1] is unlikely to be an isolated event. Our data are consistent with the hypothesis that a subset of GTD indeed may exist which is characterized by more than two copies of chromosome 8. The present findings corroborate those recently found in breast, prostate, and other cancers.

Adult↗
PubMed1997

Acute risperidone overdose.

Risperidone (Risperdal) is a recently released novel antipsychotic medication. It is different from the conventional neuroleptics, such as haloperidol, as it has both serotinergic and dopaminergic activity. It has a more tolerable side-effect profile compared with other antipsychotic medications. We review the literature regarding the side effects of risperidone use, describe a case of overdose with risperidone, and discuss the clinical sequelae and management of such an overdose.

Adult↗
PubMed1997

Stage I and stage II infiltrating ductal carcinoma of the breast analyzed for chromosome 8 copy number using fluorescent in situ hybridization.

We previously reported the results of 30 informative samples (from a total of 34 specimens gathered) of archival breast cancer tissue, including infiltrating ductal carcinoma (NOS), ductal carcinoma in situ, lobular carcinoma, papillary carcinoma and benign lesions of the breast. The study was conducted using fluorescent in situ hybridization (FISH) and a chromosome 8 alpha-satellite probe. Subsequently, a total of 34 cases of infiltrating ductal carcinoma of the breast (NOS, 17 cases stage I and 17 cases stage II) were studied, again using interphase cytogenetics. The aim of the present study is to confirm and extend the results of our initial study of stage I and stage II disease. Towards this end, 36 additional specimens of formalin-fixed paraffin-embedded breast cancer tissue have been analyzed cytogenetically under blinded conditions for the frequency of abnormal chromosome 8 copy numbers using FISH and the previously described protocol optimized for our laboratory. Of these, 18 were stage I and 18 were stage II. The frequency of trisomy 8 among stage I tumors was found to be 28% (5 out of 18). The frequency of trisomy 8 among stage II tumors was found to be 61% (11 out of 18). These results, while less striking, are consistent with those reported in our initial study of stage I and stage II disease, where the frequencies of trisomy 8 among stage I and stage II tumors were 24% (4 out of 17) and 82% (14 out of 17). These results not only establish that chromosome 8 trisomy is a recurrent finding in breast cancer, but also confirm that a higher frequency of trisomy 8 was observed with a higher clinical stage (stage II) than with a lower stage (stage I). It will be of interest to extend the findings in stage I and stage II breast cancer to other stages as well.

Adult↗
PubMed1997

Systemic immune response to Acanthamoeba keratitis in the Chinese hamster.

Recrudescence is a common and troubling feature of Acanthamoeba keratitis and suggests that corneal infection with this organism fails to stimulate the systemic immune apparatus. The present study examined the cell-mediated and humoral immune responses to Acanthamoeba keratitis in the Chinese hamster. Corneal infection with A. castellanii failed to induce either delayed-type hypersensitivity (DTH) or serum IgG antibody against parasite antigens. The failure to induce cell-mediated and humoral immunity did not result in anergy or tolerance since subsequent intramuscular (i.m.) immunization with parasite antigens elicited robust DTH and IgG antibody responses. The inability of corneal infections to induce primary cell-mediated immune responses was due to the absence of resident antigen-presenting cells in the central cornea because induction of Langerhans cell (LC) migration into the central cornea prior to infection with Acanthamoeba promoted the development of parasite-specific DTH. Although the presence of resident LC did not promote the development of a primary humoral immune response, subsequent i.m. immunization elicited heightened parasite-specific IgG antibody production which was indicative of an anamnestic response. Collectively, the results indicate that in the absence of resident antigen-presenting cells, corneal infection with Acanthamoeba fails to stimulate primary cell-mediated or humoral immunity. Induction of peripheral LC into the central corneal epithelium promotes the development of parasite-specific DTH, but does not exacerbate corneal disease.

Acanthamoeba↗
PubMed1996

Study design and baseline characteristics of the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E: SECURE.

Atherosclerotic cardiovascular disease remains a major cause of mortality and morbidity in most developed countries. Experimental and clinical evidence suggests that angiotensin-converting enzyme inhibitors and vitamin E therapy may retard the atherosclerotic process; however, definitive proof in humans is lacking. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE) is designed to assess the effects of ramipril--an angiotensin-converting enzyme inhibitor, at 2 doses: 2.5 mg daily (which has little effect on lowering blood pressure) and 10 mg daily--and the antioxidant vitamin E, 400 IU daily, on atherosclerosis progression in 732 patients using a factorial 3 x 2 study design. High-risk patients with a documented history of significant cardiovascular disease or with diabetes and additional risk factors were enrolled and will be followed for 4 years. The extent and progression of atherosclerosis are assessed noninvasively by B-mode carotid ultrasonography. The SECURE trial is a substudy of the larger Heart Outcomes Prevention Evaluation (HOPE) study of 9,541 high-risk patients evaluating the effects of ramipril and vitamin E on major cardiovascular events (cardiovascular death, myocardial infarction, and stroke). The 2 studies are complementary. Whereas HOPE is expected to provide information on major clinical outcomes, SECURE will shed light on the mechanisms by which these effects may be mediated.

Aged↗
PubMed1996

Overexpression of the normal phosphoribosylpyrophosphate synthetase 1 isoform underlies catalytic superactivity of human phosphoribosylpyrophosphate synthetase.

To define the enzymatic and genetic basis of X-linked phosphoribosylpyrophosphate synthetase (PRS) catalytic superactivity, we measured concentrations of X-linked PRS1 and PRS2 isoforms in cultured fibroblasts and lymphoblasts by immunoblotting after separation by polyacrylamide-urea isoelectric focusing. PRS1 comprised >80% of measurable PRS isoforms in all fibroblast strains, but PRS1 concentrations in cells from six affected males exceeded those in normal cells by 2-6-fold. PRS absolute specific activities (activity per mg of PRS isoforms) were comparable in all fibroblast strains and in purified recombinant normal PRS1, confirming selectively increased levels of PRS1 isoform as the enzymatic basis of PRS catalytic superactivity. Cloning, sequencing, and expression of normal subject- and patient-derived PRS cDNAs predicted normal translated region sequences for both PRS isoforms and revealed no differences in catalytic properties of recombinant PRS1. Normal and patient PRPS1 transcribed but untranslated DNA sequences were also identical. Northern blot analysis showed selective increase in relative concentrations of PRS1 transcripts in patient fibroblasts. In PRS catalytic superactivity, overexpression of the normal PRS1 isoform thus appears to result from an altered pretranslational mechanism of PRPS1 expression. In lymphoblasts, however, expression of this alteration is attenuated, explaining the absence of phenotypic expression of PRS catalytic superactivity in these cells.

Base Sequence↗