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Biomedical subjects

D Summers

Publications and source records attributed to D Summers.

At least 37 records · Page 2Linked to original sources
PubMed1994

Localization of the genetic locus for Saethre-Chotzen syndrome to a 6 cM region of chromosome 7 using four cases with apparently balanced translocations at 7p21.2.

Saethre-Chotzen syndrome is a common autosomal dominant form of craniosynostosis, which results in the premature fusion of cranial sutures. Craniosynostosis is commonly associated with abnormalities of 7p; Vortkamp et al. (Nature 352, 539-540) demonstrated that the GLI3 gene in 7p13 was disrupted in, patients with Greig syndrome and, more recently, the linkage of genetic markers from 7p with the Saethre-Chotzen syndrome locus has been reported (2,3). Here we report the analysis by fluorescence in situ hybridization of four patients with Saethre-Chotzen syndrome associated with apparently balanced translocations involving band 7p21.2 and different reciprocal chromosomes. We show that in all four patients the breakpoints in 7p are situated within a 6 cM region flanked by the genetic markers D7S488 and D7S493. These results provide further evidence that the genetic locus for Saethre-Chotzen syndrome is located in distal 7p.

Acrocephalosyndactylia↗
PubMed1994

Close linkage of a gene for X linked deafness to three microsatellite repeats at Xq21 in radiologically normal and abnormal families.

We have used three highly polymorphic microsatellite repeats from Xq21 to type families in whom a gene for X linked deafness with perilymphatic gusher (DFN 3) was segregating. All three markers were tightly linked to the disease in its radiologically normal and abnormal forms, with a maximum lod score of 10.37 with DXS995 and 8.44 with DXS986 at zero recombination, and 14.03 with DXS1002 at theta = 0.01. In an isolated case of deafness of this type, DXS995 indicated either the first recombination observed between the marker and the disease gene or a new mutation in the proband. Southern blotting using a cosmid fragment from the candidate region has confirmed a de novo mutation by showing a deletion in the proband which is not present in his mother as judged by dosage analysis. We also describe a family with a paracentric inversion associated with a microdeletion and discuss how deletion mapping using these and other markers in the region has helped to define a candidate region for the gene.

Base Sequence↗
PubMed1993

Cytogenetic evidence that the Saethre-Chotzen gene maps to 7p21.2.

Evidence for the location of the Saethre-Chotzen acrocephalosyndactyly mutation on 7p21-22 is based on genetic linkage studies in families segregating for this autosomal dominant disorder. Linkage studies were guided by several reports of chromosome deletions in this region giving rise to craniosynostosis and some other manifestations of Saethre-Chotzen syndrome. We report on a family where a father and daughter carry an apparently balanced t(7;10)(p21.2;q21.2) translocation (de novo in the father) and have the Saethre-Chotzen syndrome. These observations support the localization of the Saethre-Chotzen gene to 7p21.2.

Acrocephalosyndactylia↗
PubMed1993

Chaos in a periodically forced predator-prey ecosystem model.

We subject to periodic forcing the classical Volterra predator-prey ecosystem model, which in its unforced state has a globally stable focus as its equilibrium. The periodic forcing is effected by assuming a periodic variation in the intrinsic growth rate of the prey. In nondimensional form the forced system contains four control parameters, including the forcing amplitude and forcing frequency. Numerical experiments carried out over sections of the parameter space reveal an abundance of steady-state chaotic solutions. We graph Poincaré maps and calculate Lyapunov exponents and fractal dimensions for a representative selection of strange attractors. The transitions to chaos were found to be either via a Feigenbaum cascade of period-doubling bifurcations or via frequency locking.

Animals↗
PubMed1993

Use of the frequency-tracking locus in estimating the degree of respiratory entrainment in preterm infants.

In order to define the complex interactions between external stimuli and non-linear physiological systems, a technique (the frequency-tracking locus, FTL) was devised that describes the cycle-by-cycle changes in phase angle and amplitude between two signals. Qualitative assessment of the nature of interactions between the signals can be made by examining the FTL. Quantitation of the extent of entrainment of the spontaneous physiological rhythm is possible after deriving a numerical index (the path-length index, PLI) describing the departure of the system from a fully entrained state. The FTL was applied to the study of interactions between spontaneous respiratory effort and mechanical inflation in preterm newborn babies undergoing mechanical ventilation. Stable and unstable states of 1:1 interaction were noted while integer-ratio relationships were seen at low rates of mechanical ventilation. Stable states of entrainment corresponded to a PLI value near unity, and the value of PLI increased rapidly as interactions became unstable. The FTL may be used to describe complex interactions in physiological systems, and may be used as a guide to baby-ventilator matching during mechanical ventilation of the newborn.

Humans↗
PubMed1991

Disturbed nonlinear multispecies models in ecology.

We analyze a disturbed form of the general Lotka-Volterra model of an ecosystem with m interacting species. The disturbances act on the intrinsic growth rates of the species and are assumed to be bounded but otherwise unknown. We employ a Lyapunov technique and the concept of "reachable set" from control theory to estimate the set of all possible population densities that are attainable as a result of the disturbances. To calculate estimates for this reachable set, a number of numerical methods that entail the solution to one or more global optimization problems are developed. Specific examples involving two, three, and four species are solved. We also derive an explicit analytical expression that represents an estimate for the reachable set in the m-dimensional case. The estimate is conservative but can be evaluated without carrying out any optimization procedure. We show that methods developed in this paper can be applied to certain other types of nonlinear ecosystem models.

Animals↗
PubMed1991

Translation of hepatitis A virus RNA in vitro: aberrant internal initiations influenced by 5' noncoding region.

Hepatitis A virus (HAV) RNAs were translated in vitro in rabbit reticulocyte lysates. The pattern of proteins synthesized from full-length HAV RNA was highly complex, consisting of a continuous spectrum of polypeptides ranging from less than 20,000 to greater than 200,000 Da. The pattern was not significantly altered by varying incubation times, ion, or other reaction parameters, or by the addition of HeLa or BS-C-1 cell extracts to the translation reactions. Plasmids engineered with mutations in the 3C coding region produced transcripts which directed the synthesis of the same overall pattern of polypeptide products as those transcribed from wild-type sequences, suggesting that protein processing by 3C did not generate the complex set of protein products. Translation of RNA containing only the P3 coding region of HAV, directly adjacent to the HAV 5' noncoding region, generated a set of protein products which precisely matched a subset of those synthesized from full-length HAV RNA. The translation products of P3 RNA, full-length RNA, and mutant 3C-containing RNAs were analyzed by immunoprecipitation with antisera specific for 3D, VP1, and 2C sequences; several products were subjected to N-terminal sequence analysis. All together, the results demonstrate that translation of HAV RNA in rabbit reticulocyte lysates initiates predominantly at a large number of internal AUG codons, especially those in the P3 coding region. A minor population of products is initiated from sites in the P1 and P2 regions. The latter proteins undergo some proteolytic processing, at unidentified sites, catalyzed by 3C protein sequences. Replacement of the HAV 5' noncoding region with encephalomyocarditis virus 5' end sequences increased initiation at the correct polyprotein start site and both reduced and altered the products generated by internal initiation.

3C Viral Proteases↗
PubMed1991

Miller-Dieker syndrome with ring chromosome 17.

A girl presented at 6 weeks of age with failure to thrive and arching of the back. She had various dysmorphic features, hepatosplenomegaly, and developmental delay. The electroencephalogram and cranial ultrasound were abnormal, and a computed tomogram showed lissencephaly and apparent agenesis of the corpus callosum. Because of frequent aspiration she became oxygen dependent. She later developed intractable convulsions and died at the age of 9 months.

Abnormalities, Multiple↗
PubMed1989

The association of Angelman's syndrome with deletions within 15q11-13.

The inheritance of Angelman's syndrome, a disorder characterised by mental retardation, epilepsy, ataxia, and a happy disposition, is debated because affected sibs occur less frequently than expected with autosomal recessive inheritance. After discovering two unrelated patients with a small deletion of the proximal long arm of chromosome 15, 10 further patients with Angelman's syndrome were reassessed. Five had apparently normal karyotypes, four had a deletion within 15q11-13, and one had a pericentric inversion, inv(15)(p11q13) involving the same chromosomal region. In the latter case, the healthy mother had the same pericentric inversion, indicating that the patient also had a submicroscopic mutation on his other chromosome 15. These data map the Angelman locus to 15q11-13 and suggest that de novo visible deletions (associated with a low recurrence risk) and autosomal recessively inherited cases combine to give an overall sib recurrence risk of less than 25%.

Ataxia↗
PubMed1987

cDNA probes of individual genes of human rotavirus distinguish viral subgroups and serotypes.

The use of cDNA probes for detection of rotaviruses has been investigated using plasmids containing inserts specific for each of the eleven genes of human rotavirus strain Wa. In a dot-blot detection system in which radioactive DNA probes were hybridized to viral RNA extracted from cultivatable rotavirus strains, cDNAs of genes 7, 8, 10 and 11, were found to be the most reliable probes for detecting a range of rotavirus strains. Unexpectedly, rotaviruses could be distinguished with respect to subgroup and subtype specificities when cDNAs of genes 6 and 9, which encode the immunologically relevant proteins VP6 (group-specific antigen) and VP7 (type-specific antigen), were used as probe, even though the nucleic acid sequences of these genes are known to have a high degree of sequence homology.

Child, Preschool↗
PubMed1985

Molecular cloning and characterization of the genome of wound tumor virus: a tumor-inducing plant reovirus.

The double-stranded RNA genome of the tumor-inducing plant pathogen, wound tumor virus, was converted to double-stranded DNA and cloned into plasmid pBR322. Multiple apparent full-length copies of 9 of the 12 wound tumor virus genome segments were identified. The entire sequence of cloned genome segment S12, the smallest of the genome segments, was determined. This genome segment was found to be 851 nucleotides in length and to possess a single long open reading frame that extends 178 codons from the first AUG triplet (residues 35-37): information sufficient to encode a protein of the size estimated for the smallest of the previously identified wound tumor virus primary gene products, Pns 12. Sequence data obtained from analysis of cloned cDNA copies of several genome segments and from direct analysis of the 3' termini of the double-stranded genome RNAs revealed that each wound tumor virus genome segment possesses the common terminal sequences: (+) 5'GGUAUU ... UGAU 3' (-) 3'CCAUAA ... ACUA 5'.

Base Sequence↗
PubMed1985

Biomechanical time-tolerance of fresh cadaveric human spine specimens.

Changes in the biomechanical properties of fresh cadaveric spinal specimens due to long-term freeze storage and long test periods have been investigated. Fresh cadaveric specimens were divided into three groups: Group A specimens were tested fresh on the 1st day and 13 subsequent days; Group B specimens were tested on the 1st day, frozen in sealed bags at -18 degrees C for 21 days, and tested for 13 consecutive days after thawing; and Group C specimens were frozen for up to 232 days and tested for 14 consecutive days after thawing. We could not find any significant differences between the behavior of the three test groups. This implies that freezing and storage, even for long periods, do not significantly alter the physical properties of cadaveric spinal specimens. Concerning the differences observed on a daily basis, the mean value of the maximum displacement for the 1st day did not differ significantly from the corresponding mean value for the 13 consecutive days. This was true for all three groups, although there was some indication that the fresh group specimens showed greater variation than the two frozen groups.

Adult↗
PubMed1985

Multimer resolution systems of ColE1 and ColK: localisation of the crossover site.

We have identified and characterised a stability function encoded by the high copy plasmid ColK. The function is analogous to ColE1 cer and maximises stability by maintaining plasmids in the monomeric state. In vivo recombination between cer and ckr (which share more than 90% homology at the DNA sequence level) produced a functional hybrid. Sequence analysis of hybrids indicates that recombination involving cer and ckr is site-specific and occurs within a 35 bp region of DNA which contains palindromic symmetry.

Bacteriocin Plasmids↗
PubMed1985

Diagnosis of rotavirus infection with cloned cDNA copies of viral genome segments.

The diagnostic potential of cloned cDNA copies of human rotavirus (strain WA) genome segments for the detection of rotavirus in clinical specimens has been determined. A hybridization assay in which a mixture of 32P-labeled cDNAs representing the 11 rotavirus segments was used as a probe compared favorably with three frequently used diagnostic tests for rotavirus in terms of both specificity and sensitivity. Significantly, clinical isolates could be readily distinguished when cloned cDNA copies of individual genome segments were used independently as a probe. In assays in which genome RNA from rotaviruses of known subgroups and serotypes were tested, cloned probes that encode nonstructural viral proteins hybridized efficiently to genome RNAs of all strains, whereas cloned probes corresponding to genome segments 6 and 9 exhibited the potential for differentiating strains of different subgroups and serotypes. Cloned cDNA copies of rotavirus genome segments therefore offer considerable potential for improved general diagnosis of rotavirus in clinical specimens, as well as for epidemiological studies in which virus isolates can be distinguished on the basis of nucleotide sequence homology of individual genome segments.

Cloning, Molecular↗