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Biomedical subjects

A West

Publications and source records attributed to A West.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comparison of fluorine-18 deoxyglucose and O-15 water PET in temporal lobe epilepsy.

This study reports a comparison of Fluorine-18 deoxyglucose positron emission tomography (FDG-PET) and O-15 water (H2(15)O) PET with regard to lateralization of the seizure focus in patients with complex partial epilepsy. The analysis of 35 patients who had an anterior temporal lobectomy for medically intractable seizures indicated that FDG- and H2(15)O-PET were highly correlated in demonstrating the epileptic focus. FDG- and H2(15)O-PET showed significant asymmetries in 83% and 77% of cases respectively. The lateralization with visual analysis of MRI was found to be lower than both FDG and blood flow imaging. Ictal electroencephalography (EEG) lateralizations were concordant with sites of blood flow and FDG-PET abnormalities. Thirty-three patients (94%) were seizure-free or improved significantly after surgery. In conclusion, blood flow PET yielded similar results compared to FDG-PET and can be a valuable modality in preoperative evaluation of patients with temporal lobe epilepsy.

Adolescent↗
PubMed1999

Development of a protocol for the automated analysis of amino acids in brain tissue samples and microdialysates.

An automated precolumn derivatisation method has been developed for the measurement of fourteen amino acids in brain tissue and microdialysate samples. The method involves labelling amino acids with naphthalene-2,3-dicarboxaldehyde (NDA) in the presence of cyanide (CN-). The resulting highly stable N-substituted 1-cyanobenz[f]isoindole (CBI) derivatives were separated using a binary gradient elution profile and detected fluorometrically. The order of elution of the derivatised amino acids was confirmed by using liquid chromatography with fluorescence and mass spectrometric detection in tandem. Linear calibration plots were obtained for all amino acids in the range studied (0.2-12.5 microM). The limit of detection for CBI derivatives of amino acids was in the range 5-20 fmol (S/N=2) using a 5 microl injection volume. The method has been used for the measurement of amino acids in microdialysates from rat brain and tissue homogenates from different regions of mouse brain.

Amino Acids↗
PubMed1999

The inhibition of human cytomegalovirus (hCMV) protease by hydroxylamine derivatives.

Aryl hydroxylamine derivatives have been synthesised that are some of the most potent inhibitors of hCMV protease prepared to date (IC50 14-60 nM). Mass spectrometry studies indicate that oxazinone derived hydroxylamines inhibit the enzyme by acylation of Ser132 whereas non-oxazinone derived hydroxylamines appear to inhibit via formation of a sulfinanilide at Cys138.

Amino Acid Sequence↗
PubMed1999

Effects of alcohol on body-sway patterns in human subjects.

The vestibulospinal aspects of vestibular function are commonly neglected in the evaluation of alcohol-induced intoxication. Thus, in the present study the effect of an acute intoxication with a low or moderate quantity of alcohol was examined with respect to the equilibrium in 30 healthy subjects. The blood alcohol concentration (BAC) was measured 30 min after the ingestion of the last alcohol, ranging between 0.22 and 1.59 per thousand. Stability of stance was quantified by static platform posturography in Romberg-test conditions with eyes open and eyes closed. Among other parameters, the average body sway path (SP) and area of body sway (SA) were assessed. Posturography revealed a significant increase in body sway. There was a positive correlation between SA (or SP) and BAC both with eyes open and eyes closed. Multiple group comparisons revealed that the large-alcohol-dose group (BAC > or = 1.0 per thousand) could be clearly differentiated from test cases with BAC lower than 0.8 per thousand. Sway area was the most sensitive parameter for detecting increased body sway after alcohol ingestion. The area increase, present not only with eyes closed but with eyes open, revealed an inadequate compensation of the ethanol-induced ataxia by visual stabilization. The Romberg's quotient, which denotes eyes closed relative to eyes open, remained constant. The increase in sway path with eyes closed showed an omnidirectional sway. A comparison of the sway pattern of subjects after acute ethanol ingestion with the data of patients with permanent cerebellar lesions suggested that the acute effect of alcohol resembles that of a lesion of the spinocerebellum. This finding contrasts with earlier studies, which postulated an acute effect of ethanol resembling that in patients with an atrophy of the anterior lobe of the cerebellum due to chronic alcohol abuse. In seven cases of the lower dose group (BAC < or = 0.8 per thousand), a reduction in body sway after alcohol ingestion was observed. This finding may be consistent with a dose-related biphasic action of alcohol, which - besides its well-known depressant effects with high doses - also shows stimulatory action with small doses.

Adult↗
PubMed1999

Virus removal by filtration.

Advances in membrane technology have allowed the expansion of the size-exclusion removal principle to viruses of concern in the processing of pharmaceutical drug products derived from biological fluids and cell-culture techniques. Direct flow- and cross-flow filters are complementary techniques for virus removal and may be used either independently or as an adjunct to other virus clearance methods. Representative virus titre reduction data for microfiltration and ultrafiltration membranes are presented along with a validation model using bacteriophages as challenge viruses. Non-destructive filter integrity tests before and after filtration and a stringent process validation regime are applied to enhance product safety.

Animals↗
PubMed1998

Benzothiopyran-4-one based reversible inhibitors of the human cytomegalovirus (HCMV) protease.

A novel class of CMV protease inhibitors based on a benzothiopyran-S,S-dioxide nucleus has been discovered. Enzyme kinetic data supports a reversible mode of inhibition for a representative member of this class, 2-(3-pyridyl-N-oxide)benzothiopyran-4-one-S,S-dioxide, 1. Experiments in the presence and absence of the disulfide reducing agent DTT suggest that the inhibition by 1 is not due to oxidative inactivation of the enzyme. Also presented are results of some SAR studies of the benzothiopyranone ring system.

Amino Acid Sequence↗
PubMed1998

Chromosome localization and genomic structure of the KiSS-1 metastasis suppressor gene (KISS1).

The identification and sequence of KiSS-1 (HGMW-approved symbol, KISS1), a human malignant melanoma metastasis-suppressor gene, was recently published. In this report, we present a corrected genomic sequence, genomic structure, and refined chromosomal location for KiSS-1. The genomic organization of the sequence reveals a gene consisting of four exons. The first two exons are not translated; the third exon contains 38 5' noncoding bases followed by the translational start site and another 100 translated bases. The terminal exon contains a further 332 translated bases, the translational stop codon, and the polyadenylation signal. The gene maps to chromosome 1q32 as determined by radiation hybrid mapping and FISH analysis. The relatively simple organization of this gene will facilitate analyses for mutations and abnormal expression in human tumors.

Amino Acid Sequence↗
PubMed1998

Apoptotic response of spermatogenic cells to the germ cell mutagens etoposide, adriamycin, and diepoxybutane.

In testis, apoptosis is a way to eliminate damaged germ cells during their development. In this study, we evaluated the ability of three germ cell mutagens to induce apoptosis (or programmed cell death) at specific stages of rat seminiferous epithelial cycle. These chemicals include the cancer chemotherapy drugs etoposide and adriamycin and the butadiene metabolite diepoxybutane. According to our results, etoposide is a very potent inducer of apoptosis in male rat germ cells and the cell types most sensitive to it include all types of spermatogonia, zygotene, and early pachytene spermatocytes and meiotically dividing spermatocytes. Also, adriamycin causes an increase in apoptosis at specific stages of seminiferous epithelial cycle and the most sensitive cell types are type A3-4 spermatogonia, preleptotene, zygotene, and early pachytene spermatocytes. Diepoxybutane does not cause any significant increase in the frequency of apoptosis in rat testis. In addition, we studied whether p53 is taking part in the apoptotic response of spermatogenic cells by studying the levels of p53 protein in testis before and after chemical treatment. No accumulation of p53 in testis was seen after treatment with these three chemicals. The expression of two p53-regulated genes, p21WAF1 and mdm2, was also studied but no increase in the levels of mRNA of these genes was observed after treatment. The results indicate that apoptosis should be taken into consideration when the genotoxic effects of chemicals are evaluated in germ cells.

Animals↗
PubMed1998

Proof of fatal air embolism.

Venous air embolism is a rare cause of death. Entry of gas into the circulation is caused by trauma, mostly surgical or therapeutic, and sometimes resulting from criminal intervention. The detection of air embolisms requires special precautions during autopsy. An aspirometer has to be used for the detection, measurement and storage of gas originating from the heart ventricles. The aspirometer has to be filled completely with distilled water containing two drops of Tween 80 to reduce the surface tension of the water and to prevent adherence of small air bubbles to the wall of the aspirometer. Subsequently the gas has to be analysed by gas chromatography. When the results correspond with the main criteria defined by Pierucci and Gherson [2] the diagnosis "air embolism" is justified. The technique for the detection of air embolism is simple but requires a careful procedure which is described in detail.

Autopsy↗
PubMed1998

The piloting of a group for the fathers of children with Down syndrome.

The health services often struggle in their attempts to engage and support fathers. This paper describes the piloting of a small group for the fathers of children with a disability, in this case Down Syndrome. The group is described from conception to conclusion and limitations of the study are discussed. The group approach meets a need for a proportion of fathers who prove able to explore their experiences and feelings.

Adaptation, Psychological↗
PubMed1998

Peroxisome proliferator-activated receptor-gamma agonist, rosiglitazone, protects against nephropathy and pancreatic islet abnormalities in Zucker fatty rats.

Rosiglitazone (BRL 49653), a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist and potent insulin action-enhancing agent, was given in the diet (50 micromol/kg of diet) to male Zucker rats ages 6-7 weeks for 9 months (prevention group). In this treatment mode, rosiglitazone prolonged the time to onset of proteinuria from 3 to 6 months and markedly reduced the rate of its subsequent progression. Progression was also retarded when treatment was commenced (intervention group) after proteinuria had become established (4 months; ages 24-25 weeks). In either treatment mode, rosiglitazone normalized urinary N-acetyl-beta-D-glucosaminidase activity, a marker for renal proximal tubular damage, and ameliorated the rise in systolic blood pressure that occurred coincidentally with the development of proteinuria in Zucker fatty control rats. The renal protective action of rosiglitazone was verified morphologically. Thus in the prevention group there was an absence of the various indexes of chronic nephropathy that were prominent in the Zucker fatty control group, namely, glomerulosclerosis, dilated tubules containing proteinaceous casts, a loss of functional microvilli on the tubular epithelium, and varying degrees of chronic interstitial nephritis. An intermediate pathology was observed in the intervention group. Also, pancreatic islet hyperplasia, ultrastructural evidence of beta-cell work hypertrophy, and derangement of alpha-cell distribution within the islet were prominent features of Zucker fatty control rats, but these adaptive changes were ameliorated (intervention group) or prevented (prevention group) by rosiglitazone treatment. These data demonstrate that treatment of Zucker fatty rats with rosiglitazone produced substantial protection over a prolonged period against the development and progression of renal injury and the adaptive changes to pancreatic islet morphology caused by sustained hyperinsulinemia.

Acetylglucosaminidase↗
PubMed1997

High-performance liquid chromatographic analysis of complex N-linked glycans derivatized with 2-aminoacridone.

2-Aminoacridone (2-AMAC) has been used to derivatize mixtures of N-linked oligosaccharides released from alpha(1)-acid glycoprotein and immunoglobulin G. In each case, the HPLC profile obtained for the derivatized glycans was compared to that obtained after digestion with sialidase and a two-enzyme array system made up of sialidase and alpha-fucosidase, prior to derivatization by 2-AMAC. These studies are rapid and provide a wealth of preliminary information about the degree of sialylation and core fucosylation in the corresponding parent glycans. Moreover, collection of glycans from one single injection has provided enough material for molecular weight determination by MALDI-MS analysis. In this study we have also carried out limited MS-MS studies on enriched fractions of 2-AMAC-glycans using a nanospray orthogonal quadrupole time-of-flight mass spectrometer.

Aminoacridines↗
PubMed1997

Stage-specific expression and phosphorylation of retinoblastoma protein (pRb) in the rat seminiferous epithelium.

To assess the potential role of retinoblastoma protein (pRb) in the regulation of cell cycle during spermatogenesis, the expression of retinoblastoma (Rb) mRNA and protein, as well as the phosphorylation states of pRb, in the rat seminiferous epithelial cycle, were studied. Two transcripts, 5.4 kb and 3.4 kb long, were detected in total RNA from the adult rat testis and only the 5.4 kb transcript was detected in poly (A)+-RNA from 8, 14 and 23-day old rat testes by Northern hybridization. Polysome analysis revealed that only a small portion of both Rb transcripts could be efficiently translated. By in situ hybridization, Rb mRNA was localized to germ cells from stage V pachytene spermatocytes to step 13 spermatids along the epithelial cycle. pRb immunoreactivity was detected in Sertoli cells and spermatogonia at all stages, as well as in the elongated steps 14-19 spermatids by immunohistochemistry. The amount of pRb and the phosphorylation status varied in a stage-specific manner in Western blots. These results show that pRb is expressed in the rat seminiferous epithelium in a cyclic fashion and suggest that it is involved in the regulation of proliferation of spermatogonia and maintenance of the differentiation status of Sertoli cells and spermatids.

Animals↗
PubMed1997

Comparison of HPLC and CE for the analysis of dichlorprop in a case of intoxication.

A 49-year-old white male was found lying unconscious at home. He had vomited, his mouth was filled with a white foam and a pungent odour filled the room. After emergency treatment blood, urine and stomach contents were screened for drugs after acid and alkaline extraction with subsequent derivatisation and GC-MS analysis. Large quantites of 2,4-dichlorophenoxypropionic acid (dichlorprop, 2,4-DP) were found in all acid extracts. The man died 3 h later in hospital. Body fluids and tissues obtained at autopsy were analysed for 2,4-DP by high-performance liquid chromatography and capillary electrophoresis. The concentrations of 2,4-DP in cardiac blood, stomach contents, bile, liver, spleen, kidney and brain found by both methods were very similar.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1997

Inducible gene expression in mammalian cells and transgenic mice.

Advances in biomedicine have accentuated the need to develop methods to deliberately modulate gene activity. In addition to improved versions of the system based on components of the tetracycline resistance operon, several strategies have recently emerged to control gene function at the transcriptional level. Particularly promising are approaches based on non-mammalian steroid hormones, and on small molecules that bind immunophilins.

Animals↗
PubMed1997

Expression of the mouse interleukin-2 receptor gamma chain in insect cells using a baculovirus expression vector--comparison with the human common gamma chain.

The gene encoding the gamma-chain of the mouse Interleukin-2 receptor was expressed in lepidopteran insect cells using the baculovirus expression vector system. The corresponding gene was inserted under the polyhedrin promoter of the Autographa californica nuclear polyhedrosis virus and expressed in the Spodoptera frugiperda insect cell line Sf9 during viral infection. The recombinant receptor protein was identified by immunoblotting in cell lysates prepared from insect cells infected with the produced recombinant virus VL1392-mIL-2R gamma. Kinetic analysis demonstrated that the corresponding protein could be detected as an approximately 50 kDa protein already at 24 h post-infection. Intrinsic labelling with [35S]-methionine/cysteine and SDS-PAGE analysis of the recombinant baculovirus infected insect cells verified the immunoblotting data. The expressed IL-2R gamma protein could also be determined on the surface of infected insect cells by flow cytometric analysis. Comparison of the molecular weights between baculovirus expressed human and mouse IL-2R gamma chains indicated differences in the glycosylation pattern despite similar numbers of N-linked glycosylation sites.

Animals↗
PubMed1997

p21WAF1 expression during spermatogenesis of the normal and X-irradiated rat.

The cyclin dependent kinase inhibitor p21WAF1 has been shown to be upregulated during differentiation and after DNA damage in somatic cells. We examined the expression of p21WAF1 mRNA during the differentiation of germ cells in normal and X-irradiated rat testis by in situ hybridization and Northern blotting. p21WAF1 was normally expressed in primary spermatocytes of the pachytene phase, but could also be detected in round spermatids. In preparations of defined segments of the seminiferous tubules, the strongest hybridization signals were detected in the segments containing stages VII VIII and IX XII of the seminiferous epithelium. Ionizing radiation (1-12 Gy) induced the expression of p21WAF1 in a dose-dependent manner and the lowest dose that showed a clear increase in mRNA levels was 3 Gy. The p21WAF1 mRNA levels peaked after 3-4 hours, but remained high compared with the control levels during the 24-h follow-up. No change in the in situ hybridization pattern was seen when comparing unirradiated and irradiated tissue. Thus, it appears that X-irradiation induces p21WAF1 in the pachytene spermatocytes. Since p21WAF1 mRNA was found in pachytene spermatocytes and in round spermatids in normal testis, the protein may take part in the regulation of meiosis and in the 'terminal' differentiation of the male germ cells.

Animals↗