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Biomedical subjects

B J Williams

Publications and source records attributed to B J Williams.

At least 19 recordsLinked to original sources
PubMed1995

Loss of chromosome 17 loci in prostate cancer detected by polymerase chain reaction quantitation of allelic markers.

Using a polymerase chain reaction/microsatellite marker system, we demonstrated that 6 of 22 (27%) clinical stage B (early) primary prostate tumors showed loss of heterozygosity at one or more of five loci on chromosome 17. The sensitivity of this study was increased by use of a PhosphorImager and statistical analysis of replicate tumor-normal DNA pairs. Two patients showed tumor-specific interstitial loss at a locus in close proximity to the familial breast cancer gene BRCA1. These findings suggest that genes on the proximal long arm of chromosome 17 play a pivotal role in the early development of at least a subset of prostatic tumors.

Alleles↗
PubMed1995

Molecular cytogenetic analysis of a t(7;10) in a human glioblastoma cell line.

Glioblastoma multiforme (GBM) is the most malignant glial brain tumor in humans. The fact that deleted copies of chromosome 10 are observed frequently in primary GBM tumors supports the hypothesis that one or more tumor suppressor genes located on chromosome 10 occupy crucial growth control checkpoints for glial cells. Deletion mapping in primary GBM tumors using the loss of heterozygosity (LOH) test has implicated the 10q24-10qter region as one possible site for a gene. We report here on the molecular cytogenetic analysis of chromosome 10 abnormalities in a human GBM cell line, JBSA. LOH testing showed that JBSA cells were hemizygous for chromosome 10. Molecular cytogenetic analysis showed that the undeleted homologue was involved in a reciprocal translocation t(7;10)(p21;q22). The translocation breakpoint on chromosome 10 lay within band q22 between D10S19 and D10S4. The fact that JBSA cells lack one homologue of chromosome 10 and carry a translocation breakpoint on the remaining one, proximal to the smallest region of overlap reported in primary tumor deletions, suggests that 10q22 may be another possible site for a tumor suppressor gene involved in GBM.

Brain Neoplasms↗
PubMed1995

Social evaluation and cardiovascular response: an active coping approach.

Cardiovascular effects of social evaluation were examined under different task conditions. In Experiment 1, systolic responses in women were greater under public than private conditions when a fixed behavioral challenge was difficult, but not when the challenge was easy. In Experiment 2, social evaluation potentiated systolic responsivity in men and women when a behavioral challenge was unfixed, but not when a behavioral challenge was fixed and easy to meet. Results are discussed in terms of a recent integrative analysis of effort and cardiovascular response as well as alternative conceptions that posit, or might be taken to imply, an association between publicity and physiologic activation.

Adaptation, Psychological↗
PubMed1995

Mutation of the MXI1 gene in prostate cancer.

The Mxi1 protein negatively regulates Myc oncoprotein activity and thus potentially serves a tumour suppressor function. MXI1 maps to chromosome 10q24-q25, a region that is deleted in some cases of prostate cancer. We have detected mutations in the retained MXI1 alleles in four primary prostate tumours with 10q24-q25 deletions. Two tumours contained inactivating mutations, whereas two others contained the identical missense mutation. Fluorescence in situ hybridization also demonstrated loss of one MXI1 allele in an additional tumour lacking chromosome 10 abnormalities. MXI1 thus displays allelic loss and mutation in some cases of prostate cancer that may contribute to the pathogenesis or neoplastic evolution of this common malignancy.

Alleles↗
PubMed1995

Cytogenetic and molecular studies of Down syndrome individuals with leukemia.

There is an increased risk of leukemia in Down syndrome (DS) patients, with estimates ranging from 14 to 30 times the incidence rate observed for chromosomally normal children. Furthermore, one type of leukemia, called "transient leukemia" (TL), occurs almost exclusively in DS infants. The basis of the association between DS and leukemia is unknown, but we and others have hypothesized that it may be influenced by the mechanism of origin of the extra chromosome. Therefore, we initiated a cytogenetic and molecular study of nondisjunction in leukemia DS individuals. To date, we have obtained blood and/or tissue samples from 55 individuals consisting of 17 cases with TL, 7 cases of acute nonlymphocytic leukemia subtype M7 (ANLL-M7, or acute megakaryoblastic leukemia, postulated to be related to TL), and 31 cases of other forms of leukemia. Analysis of these cases suggests differences between DS children with TL and those with other types of leukemia or DS individuals with no history of leukemia. Specifically, the TL and ANLL-M7 cases have a highly significant increase in the frequency of "atypical" constitutional karyotypes (i.e., mosaic trisomies, rings, and/or isochromosomes) and are almost always male. Additionally, genetic mapping studies suggest an increase in the frequency of disomic homozygosity, especially in proximal 21q, in DS individuals with TL and ANLL-M7.

Adolescent↗
PubMed1994

My new image.

Explore the source record for details and available documents.

Attitude of Health Personnel↗
PubMed1994

Evaluation of 20 archival prostate tumor specimens by fluorescence in situ hybridization (FISH).

Analysis of 20 primary prostatic tumors (local Gleason grades ranging from 1 to 4) was performed on archival material obtained from formalin-fixed, paraffin-embedded blocks. Alpha satellite probes specific for the pericentric regions of chromosomes 12, 17, X, and Y were used in fluorescence in situ hybridization (FISH) assays for the examination of aneusomies for these chromosomes. Eighty percent of specimens (16/20) showed significant loss of chromosome 17 and 55% (11/20 specimens) also showed significant loss of chromosome 12; all specimens that lost chromosome 12 lost chromosome 17. Gain of the X chromosome was observed in 40% (8/20) of specimens, all but one of which also showed loss of chromosome 17. While the specimens showing gain of the X chromosome may represent polyploid cells, only one specimen also showed significant gain of chromosomes 12 and 17, suggesting that both of these chromosomes may be lost in hyperdiploid prostate cancers. Loss of the Y chromosome was not statistically significant. This study thus indicates that loss of chromosome 17 is a frequent and likely early event in prostatic cancer.

Aged↗
PubMed1994

The anticonvulsant and behavioural profile of L-687,414, a partial agonist acting at the glycine modulatory site on the N-methyl-D-aspartate (NMDA) receptor complex.

1. The anticonvulsant and behavioural effects of the glycine/NMDA receptor partial agonist, L-687,414 (R(+)-cis-beta-methyl-3-amino-1-hydroxypyrrolid-2-one) have been investigated in rodents. 2. L-687,414 dose-dependently antagonized seizures induced by N-methyl-D,L- aspartic acid (NMDLA, ED50 = 19.7 mg kg-1), pentylenetetrazol (PTZ, ED50 = 13.0 mg kg-1) and electroshock (ED50 = 26.1 mg kg-1) when given intravenously 15 min before test, in male Swiss Webster mice but was most potent against audiogenic seizures induced by a 120 dB bell in DBA/2 mice (ED50 = 5.1 mg kg-1, i.p., 30 min before test). 3. L-687,414 also induced impairments of performance in a rotarod test in both Swiss Webster and DBA/2 mice and the ratio [rotarod MED:anticonvulsant ED50] varied between 0.9 and 5, depending on the convulsant used. 4. Similar behaviours to those seen after administration of the non-competitive NMDA receptor antagonist, MK-801 (head weaving, body rolling, hyperlocomotion) were seen in the mouse after giving L-687,414, although the peak effect occurred at a dose (100 mg kg-1) which was 5-20 times the anticonvulsant ED50S, depending on the convulsant used. Unlike MK-801, however, doses of L-687,414 that were behaviourally stimulant did not increase dopamine turnover in the nucleus accumbens. 5. Consistent with the interaction of L-687,414 with the glycine/NMDA receptor, the anticonvulsant, ataxic and motor stimulant effects of the compound were significantly attenuated by the glycine/NMDA receptor agonist, D-serine (10-100 micrograms per mouse, i.c.v.). 6. The results show that L-687,414 is a potent, orally active anticonvulsant with a more benign pharmacological profile than antagonists acting at the ion channel of the NMDA receptor complex. The compound is a useful tool with which to probe the functional role of the glycine co-agonist site in vivo.

Animals↗
PubMed1993

Cyclic peptides as selective tachykinin antagonists.

Twenty homodetic cyclic peptides based on the C-terminal sequence of substance P were prepared (Table I) by a combination of solid-phase techniques and cyclizations using azide coupling procedures. Incorporation of dipeptide mimics based on substituted gamma-lactams were used in some cases to restrict their conformational mobility. Five of these cyclic peptides were shown to have high tachykinin antagonist activity (pA2 > 6) at NK-2 receptors (rat vas deferens). The two most potent of this series, XVII, cyclo(Gln-Trp-Phe-Gly-Leu-Met) (pA2 = 8.1), and I cyclo(Gln-Trp-Phe(R)Gly[ANC-2]Leu-Met) (pA2 = 6.7), were selective for NK-2 receptors compared with the other tachykinin receptors (Table II).

Amino Acid Sequence↗
PubMed1993

Difficulty as a determinant of cardiovascular response: moderating effect of instrumentality in an alleviation paradigm.

Female subjects performed 40 trials of an easy or difficult digit-recognition task while being exposed to intermittent presentations of a noxious noise. Half (high instrumentality) were told that, if they performed well, there was a high chance that they would work without noise in a subsequent trial period. The rest (low instrumentality) were told that, if they performed well, there was a low chance that they would work without noise in the subsequent trial period. Thus, a good performance insured either a high or low probability of alleviating the aversive stimulus. Results indicated that systolic responsiveness was proportional to task demand when the instrumentality of alleviative behavior was high, but low under both task conditions when the instrumentality of alleviative behavior was low. Reaction time and performance data were generally consistent with the view that these effects were due to group differences in task engagement, or 'active coping'. The main findings conceptually replicate and extend results from two previous studies that crossed difficulty and instrumentality manipulations. They also call further into question familiar theoretical conceptions that intimate direct effects of incentive value and perceived control on cardiovascular reactivity.

Adaptation, Psychological↗
PubMed1993

Ultraviolet recall associated with etoposide and cyclophosphamide therapy.

Ultraviolet recall (UR) or sunburn reactivation is an infrequently reported phenomenon. It is characterized by an erythematous eruption in the distribution of previous ultraviolet-induced sunburn. The timing of the eruption correlates well with the speculation that it is induced by the administration of a chemotherapeutic agent(s). The case of a young man who developed UR after treatment with etoposide (VP16) and cyclophosphamide is reported.

Adult↗
PubMed1992

Interactive effects of difficulty and instrumentality of avoidant behavior on cardiovascular reactivity.

College-aged subjects performed 35 trials of an easy or difficult digit-recognition task. Half were told that a good performance would ensure a high chance of avoiding a blast of noise, and half were told that a good performance would ensure a low chance of avoiding the noise. Results indicated that heart rate and systolic blood pressure reactivity were higher in the difficult condition than in the easy condition only when the probability of avoiding the noise (given success) was high. When the probability of avoiding the noise (given success) was low, heart rate and systolic responsivity were low regardless of task difficulty. It also was found that (1) performance quality was poorer overall among difficult subjects than among easy subjects, and (2) that the difference in performance quality between the easy and difficult groups was somewhat (not significantly) greater in the low-probability conditions than in the high-probability conditions. Major findings are considered in terms of Obrist's reasoning regarding the psychophysiological consequences of active coping and a motivational model by Brehm, which specifies conditions under which individuals will be more and less task engaged.

Adaptation, Psychological↗
PubMed1991

Correlation of Histoplasma capsulatum polysaccharide antigen with the severity of infection in murine histoplasmosis.

We sought to determine if Histoplasma capsulatum polysaccharide antigen (HPA) levels correlate with the extent of infection in murine of histoplasmosis. Separate groups of mice were inoculated intratracheally with varying numbers of H. capsulatum yeast cells. After 1 week, HPA levels and fungal burden (quantitative culture of lung and spleen and histopathologic stain of lung) were determined in lung and spleen, and HPA levels in serum. HPA levels, cultures and histopathological stain results of lung and spleen tissue showed a direct correlation with increasing inoculum size. HPA levels in serum also correlated with the size of inoculum. H. capsulatum antigen in lung correlated with silver stain scores of lung tissue, (R = 0.948, P less than 0.001) and with quantitative culture scores of lung, (R = 0.929, P less than 0.001). HPA levels in spleen tissue also correlated with spleen culture scores, (R = 0.724, P less than 0.001). These results indicate that determination of HPA level in serum and tissue may be a useful test in evaluating the severity of diseases as well as efficacy of antifungal therapy in histoplasmosis.

Animals↗
PubMed1991

Kynurenic acid derivatives. Structure-activity relationships for excitatory amino acid antagonism and identification of potent and selective antagonists at the glycine site on the N-methyl-D-aspartate receptor.

Derivatives of the nonselective excitatory amino acid antagonist kynurenic acid (4-oxo-1,4-dihydroquinoline-2-carboxylic acid, 1) have been synthesized and evaluated for in vitro antagonist activity at the excitatory amino acid receptors sensitive to N-methyl-D-aspartic acid (NMDA), quisqualic acid (QUIS or AMPA), and kainic acid (KA). Introduction of substituents at the 5-, 7-, and 5,7-positions resulted in analogues having selective NMDA antagonist action, as a result of blockade of the glycine modulatory (or coagonist) site on the NMDA receptor. Regression analysis suggested a requirement for optimally sized, hydrophobic 5- and 7-substituents, with bulk tolerance being greater at the 5-position. Optimization led to the 5-iodo-7-chloro derivative (53), which is the most potent and selective glycine/NMDA antagonist to date (IC50 vs [3H]glycine binding, 32 nM; IC50's for other excitatory amino acid receptor sites, greater than 100 microM). Substitution of 1 at the 6-position resulted in compounds having selective non-NMDA antagonism and 8-substituted compounds were inactive at all receptors. The retention of glycine/NMDA antagonist activity in heterocyclic ring modified analogues, such as the oxanilide 69 and the 2-carboxybenzimidazole 70, suggests that the 4-oxo tautomer of 1 and its derivatives is required for activity. Structurally related quinoxaline-2,3-diones are also glycine/NMDA antagonists, but are not selective and are less potent than the 1 derivatives, and additionally show different structure-activity requirements for aromatic ring substitution. On the basis of these results, a model accounting for glycine receptor binding of the 1 derived antagonists is proposed, comprising (a) size-limited, hydrophobic binding of the benzene ring, (b) hydrogen-bond acceptance by the 4-oxo group, (c) hydrogen-bond donation by the 1-amino group, and (d) a Coulombic attraction of the 2-carboxylate. The model can also account for the binding of quinoxaline-2,3-diones, quinoxalic acids, and 2-carboxybenzimidazoles.

Animals↗
PubMed1991

Subperiosteal abscesses of the orbit due to sinusitis in childhood.

This paper reports 16 cases of subperiosteal abscesses of the orbit due to acute sinusitis in childhood. They comprise 12.4% of 129 patients presenting with an 'acute orbit'. Acute ethmoidal sinusitis was the predominant cause. The typical clinical features, as well as CT scanning of the paranasal sinuses, orbit and brain, should assist in early diagnosis. If possible, the subperiosteal abscess and sinuses should be drained before loss of visual acuity or intracranial complications occur. Streptococcus milleri was the pathogen most commonly cultured. One patient in this series had intracranial complications, but no other patients had major complications and there were no deaths.

Abscess↗