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Biomedical subjects

L Jones

Publications and source records attributed to L Jones.

At least 217 records · Page 12Linked to original sources
PubMed1996

Expansion of 50 CAG/CTG repeats excluded in schizophrenia by application of a highly efficient approach using repeat expansion detection and a PCR screening set.

Studies of the transmission of schizophrenia in families with affected members in several generations have suggested that an expanded trinucleotide repeat mechanism may contribute to the genetic inheritance of this disorder. Using repeat expansion detection (RED), we and others have previously found that the distribution of CAG/CTG repeat size is larger in patients with schizophrenia than in controls. In an attempt to identify the specific expanded CAG/CTG locus or loci associated with schizophrenia, we have now used an approach based on a CAG/CTG PCR screening set combined with RED data. This has allowed us to minimize genotyping while excluding 43 polymorphic autosomal loci and 7 X-chromosomal loci from the screening set as candidates for expansion in schizophrenia with a very high degree of confidence.

Alleles↗
PubMed1996

Life expectancy of rigid gas permeable and high water content contact lenses.

PURPOSE: The purpose of this study was to evaluate the life expectancy of various rigid gas permeable (RGP) lens materials used on a daily wear basis and to compare these results with the life expectancy of a matched group of soft lens wearers. METHODS: We retrospectively analyzed the records of 600 contact lens wearing patients (300 soft contact lens users and 300 RGP lens users fit between September 1987 and September 1994. None of the subjects wore lenses on a planned replacement system. For the purpose of the study, RGP lenses were divided into three groups: < or = 40 Dk were considered low-Dk; 41-89 Dk were considered mid-Dk; and > or = 90 Dk were considered high-Dk. All soft lenses were high water content lenses (> or = 60% water content). Lenses were included if they were replaced due to loss, breakage, deposition, or poor wettability but not if replaced because of changes in fit or prescription. RESULTS: The mean (+/- SD) life-spans of each lens type in months were 19.9 +/- 17 for low-Dk RGP lenses, 15.9 +/- 13.3 for mid-Dk RGP lenses, 9.0 +/- 8.2 for high-Dk RGP lenses, and 6.4 +/- 5.2 for high water content soft lenses. Statistical analysis using a one-way ANOVA on ranks indicated that these results were statistically significant (P < 0.0001). CONCLUSIONS: Patients should be informed that high-Dk lenses (RGP and soft) provide substantial clinical benefits and that they should except to replace high-Dk RGP lenses after approximately 6 months. This lends further credence to the use of high-Dk lenses on a planned replacement basis.

Adult↗
PubMed1996

Linkage, association and mutational analysis of the dopamine D3 receptor gene in schizophrenia.

This study follows the observation of an association between homozygosity of an Mscl polymorphism in exon 1 and schizophrenia, which gives rise to a glycine to serine substitution and may alter the functional properties of the receptor. Alternatively the polymorphism may not itself be of functional significance but may be in linkage disequilibrium with another genetic variant in the coding or regulatory regions. To examine the second possibility we have screened all six exons of DRD3 by single-stranded conformational polymorphism analysis (SSCP) in 36 cases and 36 controls. Our findings suggest that the gene is highly conserved since we found no other mutations which alter protein structure. However we did detect a 5-bp deletion in the 3' intronic sequence flanking exon 5 which occurred in 7-8% of subjects within both case and control samples. A single bp substitution (g to a) in exon 3, which does not alter an amino acid was found in one affected individual. In addition we carried out a linkage study of 24 families multiply affected with schizophrenia and a non-parametric linkage study of 90 affected sibling pairs. These studies give no support for either major or moderate gene effects on schizophrenia susceptibility. Finally we have extended our association sample and observe a non-significant excess of homozygotes for the Mscl polymorphism in the sample overall (chi 2 = 2.09, 1 d.f., P = 0.15). The excess of homozygotes is specific to males (chi 2 = 4.617, 1 d.f., P = 0.032) and not females (chi 2 = 0.243, 1 d.f., NS). When these data are added to our previous published data a highly significant excess of homozygotes is observed in males (chi 2 = 13.766, 1 d.f., P = 0.00021) but not females (chi 2 = 0.606, 1 d.f., NS). In conclusion the accumulated data suggest strongly that genetic variation at the DRD3 locus increases susceptibility of schizophrenia, at least in males. At present the Mscl polymorphism in exon 1 of the gene remains a candidate for bringing about functional change in the receptor but this has not been formally tested. Other coding region polymorphisms have not been detected but it remains possible that variation within the promoter may alter receptor function.

Base Sequence↗
PubMed1996

Preclinical anticancer activity of cryptophycin-8.

Cryptophycin-8 was prepared by the conversion of the epoxide group on cryptophycin-1 to a chlorohydrin. In the studies reported here, cryptophycin-8 was evaluated for preclinical activity against subcutaneous tumors of both mouse and human origin. At the highest non-toxic single course treatment, the following results were obtained (Table A). Cryptophycin-8 was less potent than cryptophycin-1 by approximately 4-fold; however, it was both more water soluble and had greater therapeutic efficacy, as demonstrated by % T/C, tumor cell log kill values, range of dose effectiveness and host cures.

Animals↗
PubMed1995

Essential Ca(2+)-binding motif for Ca(2+)-sensitive inactivation of L-type Ca2+ channels.

Intracellular calcium (Ca2+) inhibits the opening of L-type (alpha 1C) Ca2+ channels, providing physiological control of Ca2+ entry into a wide variety of cells. A structural determinant of this Ca(2+)-sensitive inactivation was revealed by chimeric Ca2+ channels derived from parental alpha 1C and alpha 1E channels, the latter of which is a neuronal channel lacking Ca2+ inactivation. A consensus Ca(2+)-binding motif (an EF hand), located on the alpha 1C subunit, was required for Ca2+ inactivation. Donation of the alpha 1C EF-hand region to the alpha 1E channel conferred the Ca(2+)-inactivating phenotype. These results strongly suggest that Ca2+ binding to the alpha 1C subunit initiates Ca2+ inactivation.

Amino Acid Sequence↗
PubMed1995

On a front line.

Like the patients, doctors in Sarajevo depend largely on humanitarian aid; everyone in the public sector has worked without pay for almost three years. The hospital is on a front line; yet the psychiatric department continues to function, even conducting large scale studies of psychosocial aspects of war in Bosnia-Hercegovina. The type of inpatient morbidity and treatment patterns have changed. A plethora of psychosocial rehabilitation programmes has emerged, including counselling, drop in centres, and attending to special needs of elderly people, schoolchildren, and women. The most prominent psychological symptoms were exhaustion at the prospect of a third winter of war and bewilderment at the Western stereotype of Bosnians as Muslim fundamentalists.

Bosnia and Herzegovina↗
PubMed1995

Mind that child.

Explore the source record for details and available documents.

Child Day Care Centers↗
PubMed1995

Autosomal dominant rolandic epilepsy and speech dyspraxia: a new syndrome with anticipation.

We describe a family of 9 affected individuals in three generations with nocturnal oro-facio-brachial partial seizures, secondarily generalized partial seizures, and centro-temporal epileptiform discharges, associated with oral and speech dyspraxia and cognitive impairment. The speech disorder was prominent, but differed from that of Landau-Kleffner syndrome and of epilepsy with continuous spike and wave during slow-wave sleep. The electroclinical features of this new syndrome of autosomal dominant rolandic epilepsy resemble those of benign rolandic epilepsy, a common inherited epilepsy of childhood. This family shows clinical anticipation of the seizure disorder, the oral and speech dyspraxia, and cognitive dysfunction, suggesting that the genetic mechanism could be expansion of an unstable triplet repeat. Molecular studies on this syndrome, where the inheritance pattern is clear, could also be relevant to identifying a gene for benign rolandic epilepsy where anticipation does not occur and the mode of inheritance is uncertain.

Adult↗
PubMed1995

Arthroscopic resection of a chondroblastoma in the knee.

A 13-year-old boy with the diagnosis of osteochondritis dissecans underwent arthroscopic examination of his knee joint. At surgery a cartilaginous mass in the medial femoral condyle was identified. Biopsy samples confirmed the diagnosis of chondroblastoma, which was removed completely through the arthroscope. A second arthroscopic examination of the knee was conducted at 6 months, and showed no residual disease. Clinical and radiographic follow-up of the affected joint 5 years after surgery was satisfactory. Arthroscopic removal of an intra-articular tumor is an attractive treatment alternative, provided the lesion is accessible and there is no suggestion of a malignancy.

Adolescent↗
PubMed1995

Persistence and transmission of tick-borne viruses: Ixodes ricinus and louping-ill virus in red grouse populations.

The population dynamics of tick-borne disease agents and in particular the mechanisms which influence their persistence are examined with reference to the flavivirus that causes louping-ill in red grouse and sheep. Pockets of infection cause heavy mortality and the infection probably persists as a consequence of immigration of susceptible hosts. Seroprevalence is positively associated with temporal variations in vectors per host, although variation between areas is associated with the abundance of mountain hares. The presence of alternative tick hosts, particularly large mammals, provides additional hosts for increasing tick abundance. Grouse alone can not support the vectors and the pathogen but both can persist when a non-viraemic mammalian host supports the tick population and a sufficiently high number of nymphs bite grouse. These alternative hosts may also amplify virus through non-viraemic transmission by the process of co-feeding, although the relative significance of this has yet to be determined. Another possible route of infection is through the ingestion of vectors when feeding or preening. Trans-ovarial transmission is a potentially important mechanism for virus persistence but has not been recorded with louping-ill and Ixodes ricinus. The influence of non-viraemic hosts, both in the multiplication of vectors and the amplification of virus through non-viraemic transmission are considered significant for virus persistence.

Animals↗
PubMed1995

Pressor response to cycle ergometry in the midtrimester of pregnancy: can it predict preeclampsia?

Ninety-seven primigravid patients were prospectively studied to assess the predictive value of the pressor response to aerobic exercise as a screening test for preeclampsia. The blood pressure response to cycle ergometry exercise to a maternal pulse of 140 beats/min was recorded on each subject. Each subject was studied in the second trimester of pregnancy at a mean gestational age of 23 weeks (range, 18 to 27). Three of the study subjects developed hypertension with proteinuria in the third trimester. A rise in systolic blood pressure of at least 30 mm Hg occurred in 29 patients, but this did not predict third trimester preeclampsia (p = 0.21). A rise in diastolic blood pressure of 20 mm was observed in 18 patients, two of whom developed preeclampsia (p = 0.08). An increase of diastolic pressure of 20 mm Hg with moderate cycle ergometry exercise in the second trimester may predict a subset of patients at elevated risk of preeclampsia in the third trimester. However, the positive predictive value of this 20 mm Hg pressor increase (11%) limits its applicability as a screening test. Thus, we cannot recommend the use of an exercise screening test at this time.

Blood Pressure↗
PubMed1995

Antigenic determinants of the OmpC porin from Salmonella typhimurium.

The antigenic determinants of Salmonella typhimurium OmpC were investigated by the analysis of cyanogen bromide (CNBr)-generated porin peptides with antiporin monoclonal antibodies (MAbs). We identified six bands (f1 to f6) with estimated molecular masses of 35.5, 31.0, 25.0, 22.5, 13.8, and 10.0 kDa, respectively. In addition, two small fragments (f7 and f8; 3.0 to 6.0 kDa) were detected only infrequently. The OmpC monomer or its CNBr-generated peptides were electrophoretically transferred to a polyvinylidene difluoride membrane and then subjected to amino acid composition analysis and N-terminal sequencing. A comparison of the amino acid composition data with known compositions of Escherichia coli and Salmonella typhi OmpC showed some differences; however, the amino acid sequences of 71 residues identified in S. typhimurium showed 88 and 98% identity with OmpC from E. coli and S. typhi, respectively. The screening of CNBr peptides with the 12 anti-(S. typhimurium) OmpC MAbs by Western blot (immunoblot), in conjunction with the prediction of the OmpC folding pattern based on the known three-dimensional structure of E. coli OmpF, showed that four MAbs reacted with surface-exposed epitopes on loops L2, L8, and L4 to L7, four MAbs reacted with a region in the eyelet structure on loop L3, and four MAbs reacted with the buried epitopes on transmembrane beta strands. The MAbs reacting with surface-exposed loops showed no cross-reaction with E. coli OmpC, whose sequence has diverged extensively from that of S. typhi and (probably) S. typhimurium OmpC only in regions of the externally exposed loops. In contrast, MAbs reacting with transmembrane beta strands, whose sequence is strongly conserved, showed strong cross-reaction with E. coli OmpC. These results show that comparison with the E. coli OmpF structure predicts the folding pattern of S. typhimurium OmpC rather accurately and that evolutionary divergence in sequences is confined to the external loops. The possible roles of these surface-exposed and buried epitopes as potentially useful antigenic regions for diagnostic assays and vaccine development are discussed.

Amino Acid Sequence↗