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Biomedical subjects

D N Black

Publications and source records attributed to D N Black.

At least 19 recordsLinked to original sources

Leukotomy revisited: late cognitive and behavioral effects in chronic institutionalized schizophrenics.

BACKGROUND: In the 1940s and 1950s, prefrontal lobotomy was widely used to treat aggressive, disruptive and psychotic behavior in schizophrenics. Subsequent observations have confirmed its ineffectiveness in schizophrenia. Few studies have addressed its long-term consequences. METHODS: We conducted tests of frontal function, behavior (Frontal Behavioral Inventory), psychopathology (PANSS), neurological examinations and CT scans in 19 chronically institutionalized schizophrenic patients (mean age 74) who had undergone orbitofrontal leukotomy between 1948 and 1972 and 11 controls (mean age 74) matched for age, length of hospitalization, education, and diagnosis. RESULTS: There were no significant differences between leukotomized patients and controls on: Folstein Mini-Mental score (leuko 22.13+/-5.66; controls 23.55+/-5.93), utilization behavior, Luria alternating written and motor sequences, verbal fluency, imitation behavior, motor impersistence, primitive reflexes, or psychopathology. Significant differences were found on clock drawing and on the go/no-go test, which may reflect the presence of an orbitofrontal lesion in the leukotomized group. There was a tendency for the leukotomized group to have fewer indices of frontal behavioral dysfunction. Both groups showed comparable impairment on the Stroop test and cognitive rigidity on the Odd Man Out test of category shifting. CONCLUSIONS: With few exceptions, elderly leukotomized and nonleukotomized schizophrenic patients show varying degrees of distractibility, difficulty in set shifting, poor planning and organization, susceptibility to interference, primitive reflexes and signs of global cognitive impairment. Allowing for the small sample size, variability in the surgical frontal lesion, and the long interval from surgery to testing, these observations likely reflect the long-term consequences of severe schizophrenia in both groups.

Aged↗

Cree leukoencephalopathy: neuroimaging findings.

PURPOSE: To describe the computed tomographic (CT) and magnetic resonance (MR) imaging findings in Cree leukoencephalopathy. MATERIALS AND METHODS: The authors retrospectively reviewed the medical records and neuroimaging studies in 12 infants with Cree leukoencephalopathy (CT in 12 infants, MR in six). The diagnosis was established clinically in six patients and at autopsy in the other six. RESULTS: At CT, extensive, diffuse, and symmetric hypoattenuation was seen in the cerebral and cerebellar white matter in all 12 patients. Hypoattenuation was also seen in the corpus callosum in 11 (92%), internal capsule in 10 (83%), globus pallidus in nine (75%), brainstem in nine (75%), and thalamus in four (33%). The caudate nucleus and putamen were spared. On T2-weighted MR images in six patients, the cerebral and cerebellar white matter, including the subcortical arcuate fibers, was hyperintense as were the internal capsule, corpus callosum, corticospinal tracts, and globus pallidus. The thalamus was affected in four (67%) patients, pons in five (83%), and medulla in four (33%). The caudate nucleus and putamen were not affected. CONCLUSION: Cree leukoencephalopathy causes striking symmetric and diffuse involvement of the cerebral and cerebellar white matter and brainstem with sparing of the caudate nucleus and putamen.

Encephalitis↗

[Neurologic sequelae secondary to acute lithium poisoning].

OBJECTIVE: To review the literature on the permanent neurological sequelae resulting from acute lithium poisoning. METHOD: Sixty-six articles were reviewed in English and in French. They were accessed through Medline and cover the period from 1968 to 1997. RESULTS: Fifty-nine case studies were broken down into 3 groups: lithium intoxications without a neuroleptic that has provoked a cerebellar syndrome; those in which there was a neuroleptic; and those with diverse neurological consequences, with or without a neuroleptic. CONCLUSIONS: Lithium has an intrinsic toxicity for the central nervous system and provokes a tropism specific to the cerebellum. The association with neuroleptics appears to increase toxicity as well as some associated factors, including infections and the rapid correction of the lithium level in the blood. We discuss the psychopathological mechanisms invoked to explain lithium's neurotoxicity.

Antipsychotic Agents↗

Trial of a capripoxvirus-rinderpest recombinant vaccine in African cattle.

Cattle were vaccinated with differing doses of an equal mixture of capripox-rinderpest recombinant viruses expressing either the fusion protein (F) or the haemagglutinin protein (H) of rinderpest virus. Animals vaccinated with 2 x 10(4) p.f.u. or greater of the combined viruses were completely protected against challenge, 1 month later, with both virulent rinderpest and lumpy skin disease viruses. Vaccination with any of the doses did not induce any adverse clinical response in the animals or transmission of the vaccine virus between animals. All cattle challenged 6 or 12 months after vaccination with 2 x 10(5) p.f.u. of the mixture of recombinant viruses were protected from severe rinderpest disease. Ten out of 18 were completely protected while the remaining 8 developed mild clinical signs of rinderpest. Cattle vaccinated with the recombinant vaccines after prior infection with the parental capripox virus showed more marked clinical signs of rinderpest after challenge with virulent rinderpest, but 9 out of 10 recovered, compared with 80% mortality in the unvaccinated controls.

Animals↗

Expression of the major core structural protein (VP7) of bluetongue virus, by a recombinant capripox virus, provides partial protection of sheep against a virulent heterotypic bluetongue virus challenge.

A recombinant capripox virus was constructed containing a cDNA copy of genome segment 7 of bluetongue virus (BTV) serotype 1 from South Africa (BTV 1SA), which expressed high levels of the major BTV core protein VP7 in infected lamb testis (LT) cells. Sheep vaccinated with this recombinant virus developed antibodies to VP7 (detected by ELISA) but no neutralizing antibodies to either the homologous or heterologous BTV serotype, prior to challenge (BTV 1 or BTV 3, respectively). Following challenge with a virulent heterotypic strain of BTV (BTV3 SA), all of the animals developed clinical signs of disease, indicating that they were infected and that the challenge virus did replicate. While all of the control animals died, six of the eight animals that were vaccinated with the recombinant capripox virus expressing VP7 recovered fully. This is the first report of a significant level of cross serotype protection against the lethal effects of a challenge with virulent BTV, produced by vaccination with a single BTV core protein, which did not generate a neutralizing antibody response.

Animals↗

Sequence analysis of HindIII Q2 fragment of capripoxvirus reveals a putative gene encoding a G-protein-coupled chemokine receptor homologue.

The DNA sequence of the HindIII Q2 fragment near the left terminus of the capripoxvirus (KS-1 strain) genome was determined. The sequence contains two complete open reading frames (ORFs) and a part of a third. Analysis of the deduced amino acid sequence of one of these ORFs, Q2/3L, revealed that this gene has the capacity to encode a protein which is related to members of the G-protein coupled chemokine receptor subfamily, the swinepoxvirus K2R and the human cytomegalovirus US28 ORFs. It has the key structural characteristics of the G-protein-coupled receptor superfamily, e.g., seven hydrophobic regions, predicted to span the cell membrane, and the cysteine residues in the first and second extracellular loops that are implicated in formation of a disulfide bond. Southern blot analysis showed that all three species of the Capripoxvirus genus, i.e., sheep pox, goat pox, and lumpy skin disease of cattle, contain copies of this putative G-protein-coupled chemokine receptor homologue.

Amino Acid Sequence↗

Protection of goats against peste des petits ruminants with recombinant capripoxviruses expressing the fusion and haemagglutinin protein genes of rinderpest virus.

Goats were protected against a lethal challenge of peste des petits ruminants (PPR) virus following vaccination with a recombinant capripoxvirus containing either the fusion (F) gene of rinderpest virus or the haemagglutinin (H) gene of rinderpest virus. The H gene recombinant produced high titres of neutralizing antibody to rinderpest virus in the vaccinated goats, whereas the F gene recombinant failed to stimulate detectable levels of neutralizing antibody. A similar response to the two recombinant vaccines has previously been reported for cattle. Neither recombinant produced detectable levels of specific antibodies to PPR virus.

Animals↗

Protection of cattle against rinderpest and lumpy skin disease with a recombinant capripoxvirus expressing the fusion protein gene of rinderpest virus.

Cattle were protected against challenge with rinderpest and lumpy skin disease viruses by vaccination with a recombinant capripoxvirus containing the fusion protein (F) gene of rinderpest virus. The minimum protective immunising doses for rinderpest and lumpy skin disease were 5.5 x 10(4) plaque forming units (pfu) and 1.5 x 10(3) pfu, respectively.

Animals↗

Recombinant capripoxvirus expressing the hemagglutinin protein gene of rinderpest virus: protection of cattle against rinderpest and lumpy skin disease viruses.

A cDNA clone containing the complete coding sequence of the hemagglutinin (H) protein gene of the RBOK vaccine strain of rinderpest virus, under the control of the vaccinia late promoter p11, was inserted by homologous recombination into the thymidine kinase gene of the KS-1 strain of capripoxvirus. The recombinant virus produced authentic H protein as judged by its electrophoretic mobility, transport to the cell surface of infected lamb testis cells, and reactivity with monoclonal antibodies specific for the H protein of rinderpest virus. The recombinant virus induced significant levels of rinderpest virus neutralizing antibodies in vaccinated cattle and protected them from clinical rinderpest after challenge with a lethal dose of a highly virulent heterologous strain of the virus. Protection was achieved using vaccine doses lower than those used with a similar recombinant expressing the fusion protein gene of rinderpest. The parental KS-1 virus is widely used as a vaccine against capripox viruses and so the rinderpest recombinant acts as a dual vaccine to protect cattle against both rinderpest and lumpy skin disease.

Animals↗

Western blot analysis of virus-specific antibody responses for capripox and contagious pustular dermatitis viral infections in sheep.

This paper reports the development and evaluation of serological tests for the differentiation of antibodies in animals infected with capripox and parapox viruses. Agar-gel immunodiffusion tests using sera from sheep with naturally-acquired infections and from sheep experimentally inoculated with orf or capripox viruses showed cross reactions. Virus-specific antibody responses to structural proteins of the viruses were analysed by Western-blot analysis. This analysis readily differentiated the infections as either capripox or contagious pustular dermatitis. The antibody responses to the 32 kDa and 26 kDa proteins of capripoxvirus provided a firm basis for differentiation.

Animals↗

Single capripoxvirus recombinant vaccine for the protection of cattle against rinderpest and lumpy skin disease.

A recombinant capripoxvirus has been constructed containing a full-length cDNA of the fusion protein gene of rinderpest virus. The gene was inserted in the thymidine kinase gene of the capripox genome under the control of the vaccinia virus major late promoter p11 together with the Escherichia coli gpt gene in the opposite orientation under the control of the vaccinia early/late promoter p7.5. A vaccine prepared from this recombinant virus protected cattle against clinical rinderpest after a lethal challenge with a virulent virus isolate. In addition, the vaccine protected the cattle against lumpy skin disease.

Animals↗

A capripoxvirus pseudogene whose only intact homologs are in other poxvirus genomes.

Equivalent regions from within the inverted terminal repeats (ITRs) of the genomes of two capripoxviruses, KS-1 and InS-1, were sequenced. The sequence from KS-1 DNA covers the major part of three contiguous open reading frames (ORFs), which match three contiguous ORFs from within the genomic ITRs of the leporipoxvirus Shope Fibroma Virus (SFV). The sequenced region of InS-1 DNA contains only two of the three ORFs. The region homologous to the third ORF has no coding potential due to the presence of several stop codons, resulting from small frameshifting deletions and insertions. The significance of a degenerate poxvirus gene, intact homologs of which are only found in other poxvirus genomes, is discussed.

Amino Acid Sequence↗

The characterization of African strains of capripoxvirus.

Isolates of capripoxvirus collected from sub-Saharan Africa were compared in sheep, goats and cattle and by restriction endonuclease digestion of their purified DNA. Biochemical techniques were used to precisely identify strains of capripoxvirus for epidemiological investigations. Strains of capripoxvirus infecting cattle have remained very stable over a 30-year period and are closely related to strains recovered from sheep in Africa.

Africa↗

Poxvirus genetic recombination during natural virus transmission.

We have compared detailed physical maps of the genomes of four capripoxvirus isolates, representing four capripoxvirus genome types. The comparisons strongly suggest that the progenitor of one of these isolates arose by genetic recombination between members of two of the other three types.

Animals↗

The nucleotide sequence around the capripoxvirus thymidine kinase gene reveals a gene shared specifically with leporipoxvirus.

We have extended previous comparisons of genetic organization between poxvirus genera by sequencing a 2.5K genomic fragment from isolate KS-1 (Kenya sheep-1) of the genus capripoxvirus. The fragment is located in the central region of the capripoxvirus genome and contains three complete and two incomplete open reading frames (ORFs). One of the complete ORFs is a gene for thymidine kinase (TK). This gene, with one of the other two complete ORFs and both the incomplete ORFs, are homologous to four contiguous ORFs from the central region of vaccinia virus (VV) DNA. They also match four ORFs of fowlpox virus (FPV) DNA, three of which are contiguous and the fourth, the FPV TK gene, is located elsewhere on the FPV genome. The third complete ORF of the capripoxvirus DNA fragment is located between the TK gene and the capripoxvirus homologue of the ORF immediately downstream of the VV TK gene. We show that a homologue to this third ORF is absent from VV and FPV DNAs, but is present downstream of the TK gene on Shope fibroma virus DNA. The sequence immediately upstream of the capripoxvirus homologue of a VV late gene contains a motif which is required for VV late gene expression. The motif required for VV early gene transcription termination is present in eight positions in the capripoxvirus sequence, and five of these positions are consistent with the motif having an equivalent function in capripoxvirus to that in VV.

Amino Acid Sequence↗