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Biomedical subjects

D J Alexander

Publications and source records attributed to D J Alexander.

At least 109 records · Page 6Linked to original sources
PubMed1991

CFC replacements: safety testing, approval for use in metered dose inhalers.

HFA-134a and HFA-227 (chlorine free hydrofluoro-alkanes) are at present in extensive nonclinical safety testing sponsored by two joint research consortia (IPACT-I, IPACT-II) of companies interested in metered dose inhalers (MDI). The rationale for toxicity testing of these CFC replacements is to predict safety of their use as drug propellants in MDI. Frequency of use, intervals and systemic exposure levels are key parameters. Intact animals and in-vitro systems repeatedly exposed to multiples of patient doses, under conditions comparable to human administration should not show adverse reactions. With an emphasis different from non-U.S. Health Authorities, the U.S. FDA insists on proof of toxic effects which may require excessive doses. This principle is questioned for essentially inert gases such as CFCs and HFA-134a and HFA-227 which only through the effects of oxygen deprivation at unreasonably high concentrations of the inhaled propellant/air mixture indirectly cause mild toxic effects in animals. Provided that no intrinsic toxic effects will be detected, chances are good that these CFC replacements will eventually be approved. In view of the estimated 5-year testing time frame and the risks involved, CFCs should remain available for MDI for some time in the future.

Administration, Inhalation↗
PubMed1990

Duck virus enteritis in Great Britain, 1980 to 1989.

During the decade 1980 to 1989, 513 submissions of material suitable for the isolation of duck enteritis herpesvirus were received. Of these, 238 (46.4 per cent) were from suspected cases of duck viral enteritis, which was confirmed by the isolation of duck enteritis herpesvirus in 106 cases. Other viruses were isolated from 86 submissions. Ninety-eight (92.5 per cent) of the confirmed cases of the disease occurred in the months April to June, and there was a noticeable increase in the number of suspected and confirmed cases in the second half of the decade.

Animals↗
PubMed1990

Echocardiographic evaluation of the spectrum of cardiac anomalies associated with trisomy 13 and trisomy 18.

To investigate the role that cardiac anomalies play in the early death frequently seen in the trisomy 13 and the trisomy 18 syndromes, two-dimensional and Doppler echocardiograms from 31 newborn infants with cytogenetic confirmation of these syndromes seen at one institution over a 4.5 year period (1983 to 1988) were reviewed. The mean age at echocardiography was 1.5 days, and the median age at death was 14 days. Significant cyanosis was present in 58%. Cardiac anomalies that would be considered lethal within the neonatal period were present in only 19% of patients. The most common lesions were atrial septal defect (81%), ventricular septal defect (61%) and patent ductus arteriosus (85%). Most ventricular septal defects and patent ductus arteriosus were large. Valvular dysplasia of one or more valves, graded as mild in most cases, was found in 68%, but was not associated with Doppler evidence of significant regurgitation or stenosis in any subject. Of the four valves, the pulmonary valve, followed by the tricuspid valve, was the most commonly dysplastic. Doppler evidence suggestive of elevated pulmonary artery pressure (low velocity bidirectional flow across the ventricular septal defect and patent ductus arteriosus), although expected, was accompanied by greater than normal mean right ventricular cavity and free wall dimensions in these patients. Thus, although the cardiac anomalies most frequently encountered in trisomy 13 and trisomy 18 are nonlethal, the combined findings of frequent cyanosis and increased right ventricular dimensions suggest that other factors such as pulmonary hypertension, perhaps related to maldevelopment of the pulmonary vasculature, may contribute to early death in some of these infants.

Abnormalities, Multiple↗
PubMed1990

Avian Paramyxoviridae--recent developments.

This paper reviews the recent developments related to members of the Paramyxoviridae family which infect avian species. These developments include: (1) The identification of the virus responsible for the diseases turkey rhinotracheitis and swollen head syndrome in chickens as a member of the Pneumovirus genus, the first of this type to be isolated from birds. (2) The use of monoclonal antibodies prepared against Newcastle disease virus (NDV) and other avian paramyxoviruses which has enabled more exact and rapid diagnosis and greater understanding of the epizootiology of these viruses. (3) The nucleotide sequencing of the genome of NDV and subsequent amino acid sequencing of the major virus proteins have resulted in greater understanding of the pathogenicity of this economically important virus.

Amino Acid Sequence↗
PubMed1989

Characterization of paramyxoviruses isolated from penguins in Antarctica and sub-Antarctica during 1976-1979.

Nine paramyxovirus isolates obtained from penguins were tested for antigenic relationships amongst themselves and to other avian paramyxoviruses. One of the isolates was shown to be a lentogenic Newcastle disease virus (NDV), i.e., of PMV-1 serotype. By serological tests and analysis of structural polypeptides the other penguin isolates could be placed into three groups. No relationship with other avian paramyxoviruses could be determined except that six of the penguin viruses, representing two of the groups, showed reaction with a monoclonal antibody raised against NDV Ulster 2C and three of the isolates, representing one of the penguin groups, also reacted with another PMV-1 directed monoclonal antibody.

Animals↗
PubMed1989

Evaluation of mouse monoclonal antibodies raised against an isolate of the variant avian paramyxovirus type 1 responsible for the current panzootic in pigeons.

Nine monoclonal antibodies raised against "pigeon variant" avian paramyxovirus type 1 isolate pigeon/England/617/83 were tested for their ability to react with "classical" and other "pigeon variant" isolates. Two of the monoclonal antibodies appeared to be specific for 617/83 reacting with no other virus. The remaining seven monoclonal antibodies bound to cells infected with all other "pigeon" isolates in indirect immunoperoxidase (IIP) tests but four distinct groups of other PMV-1 viruses were formed on the basis of the binding patterns. One of the monoclonal antibodies 161/617 caused haemagglutination inhibition (HI) of all the "pigeon" isolates tested but none of the other PMV-1 viruses and these results reflected the IIP results with this monoclonal antibody. 161/617 was also shown to inhibit viruses of the avian paramyxovirus type 3 serogroup in HI tests. This reaction and the ability to bind to infected cells in IIP tests appeared to be restricted to PMV-3 viruses isolated from exotic birds and did not occur with viruses of ostensively the same serotype from turkeys.

Animals↗
PubMed1989

Location of neutralizing epitopes on the fusion protein of Newcastle disease virus strain Beaudette C.

A panel of eight neutralizing monoclonal antibodies (MAbs) against the fusion (F) protein of Newcastle disease virus (NDV) has been shown to locate a major antigenic site on the basis of competitive binding assay and additivity index studies. Five epitopes (A1 to A5) have been located within this site on the F protein of the Beaudette C strain of NDV on the basis of cross-resistance plaque assays of MAb-resistant mutants raised against these MAbs. Epitopes A1, A4 and A5 are distinct; epitope A2 partially overlaps epitope A3. Nucleotide sequence analysis of the F genes of MAb-resistant mutants showed that each predicted single amino acid substitutions ranging from amino acid residues 157 to 171 for epitope A4 and at residues 72, 78, 79 and 343 for epitopes A1, A2, A3 and A5 respectively. These locations indicate that both the F1 and F2 fragments are involved in the formation of a single antigenic site and suggest the involvement of extensive protein folding in the active form of this F protein.

Amino Acid Sequence↗
PubMed1989

[Comparative studies of paramyxovirus isolates from wild birds].

As a result of a surveillance programme in North-Germany, paramyxovirus-isolates of serogroup 1 with different pathogenicity were isolated from different species of feral birds (Black-headed gull, mallard, tawny owl, tree sparrow, mute swan). In chick embryo fibroblast monolayers these isolates produced plaques exhibiting different plaque morphology. After cloning the isolates, further physicochemical, serological and pathogenicity testings were performed. On the basis of mean death time and intracerebral pathogenicity index, two of the isolates were found to be avirulent (lentogenic), whereas the others proved to be virulent (velogenic). SDS-Polyacrylamide-gel-electrophoresis showed polypeptide patterns similar to that of the PMV-1 reference strains. Summarizing all relevant findings of these investigations under consideration of the suggestions for the virological description of avian PMV (Alexander, 1987; Alexander et al., 1987; Who-Expert-Committee, 1980), including the recently established serotyping by means of monoclonal antibodies, the following designations of the PMV isolates tested herein are proposed: 1. PMV-1/black-headed gull/Germany/SSP-233/83, lentogenic NDV, monoclonal antibody group G 2. PMV-1/mallard/Germany/SSP-284/83, lentogenic NDV, monoclonal antibody group H 3. PMV-1/tawny owl/Germany/SSP-262/84, velogenic NDV, monoclonal antibody group B 4. PMV-1/tree sparrow nestling/Germany/SSP-352/84, velogenic NDV, monoclonal antibody group B 5. PMV-1/mute swan/Germany/SSP-204/85, velogenic NDV, monoclonal antibody group B.

Animals↗
PubMed1988

Redecoration of external leaded paintwork and lead-in-dust concentrations in school playgrounds.

Playground lead-in-dust concentrations have been measured immediately after the external redecoration of 216 schools in 1983/4 and of 63 schools in 1984/5. Schools were divided into four age categories: A, pre-1914; B, 1914-1939; C, 1945-1965; and D, post-1965. The results show that concentrations can vary widely from school to school within a given age category. For each school, dust samples were collected from an area adjacent to the facade which had been redecorated, referred to here as the 'corridor' area, and from the 'remaining' playground area. The highest mean corridor concentrations were found in playgrounds of schools of age categories A and B, the highest mean value being 74,400 micrograms g-1. The highest value for age category D schools was 2600 micrograms g-1. The mean concentration for all schools in age categories A to D, was respectively 4720, 2820, 820 and 630 micrograms g-1 for the corridor area and 1180, 730, 400 and 440 micrograms g-1 for the remaining area. The highest lead-in-dust concentrations tended to occur within 2.5 m of the building facade. A limited number of measurements showed that concentrations in the corridor area tended to reduce with time, falling to half their initial value (after correcting for the local background level) in about 90-170 days. A model is suggested linking lead-in-dust concentrations in the corridor and remaining areas to lead-in-paint debris dust concentrations.

Child↗
PubMed1987

Strain specific antibodies revealed by immunoabsorption studies with avian infectious bronchitis virus.

Rabbit antisera prepared against the Massachusetts 41 (M41) strain of avian infectious bronchitis virus (IBV) and absorbed with chick embryo immunoabsorbent produced multiple precipitin lines in immunodouble-diffusion (IDD) tests with homologous or heterologous strains of virus. These precipitin lines were all removed by absorption with concentrated M41 virus preparations, but repeated absorption with concentrated, purified preparations of IBV strains: T, Holte, Connecticut, Beaudette or H120 failed to remove all precipitin lines produced to M41 virus, although all those to the heterologous viruses were removed. The remaining line(s) produced with M41 virus by sera absorbed with different heterologous viruses showed identity in IDD tests and was associated with the surface projections of the virus.

Animals↗
PubMed1987

Molecular analyses of the hemagglutinin genes of H5 influenza viruses: origin of a virulent turkey strain.

Comparative sequence analysis of the hemagglutinin (HA) genes of a highly virulent H5N8 virus isolated from turkeys in Ireland in 1983 and a virus of the same subtype detected simultaneously in healthy ducks showed only four amino acid differences between these strains. Partial sequencing of six of the other genes and antigenic similarity of the neuraminidases established the overall genetic similarity of these two viruses. Comparison of the complete sequence of two H5 gene sequences and partial sequences of other virulent and avirulent H5 viruses provides evidence for at least two different lineages of H5 influenza virus in the world, one in Europe and the other in North America, with virulent and avirulent members in each group. In vivo studies in domestic ducks showed that all of the H5 viruses that are virulent in chickens and turkeys replicate in the internal organs of ducks but did not produce any disease signs. Additionally, both viruses isolated from turkeys and ducks in Ireland were detected in the blood. These studies provide the first conclusive evidence for the possibility that fully virulent influenza viruses in domestic poultry can arise directly from viruses in wild aquatic birds. Studies on the cleavability of the HA of virulent and avirulent H5 viruses showed that the principles established for H7 viruses (F. X. Bosch, M. Orlich, H. D. Klenk, and R. Rott, 1979, Virology 95, 197-207; F. X. Bosch, W. Garten, H. D. Klenk, and R. Rott, 1981, Virology 113, 725-735) also apply to the H5 subtype. These are (1) only the HAs of virulent influenza viruses were cleaved in tissue culture in the absence of trypsin and (2) virulent H5 influenza viruses contain a series of basic amino acids at the cleavage site of the HA, whereas avirulent strains contain only a single arginine with the exception of the avirulent Chicken/Pennsylvania virus. Thus, a series of basic amino acids at the cleavage site probably forms a recognition site for the enzyme(s) responsible for cleavage.

Amino Acid Sequence↗