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F Graham

Publications and source records attributed to F Graham.

29 records · Page 2Linked to original sources
PubMed1995

Therapeutic serum concentrations of human alpha-1-antitrypsin after adenoviral-mediated gene transfer into mouse hepatocytes.

Alpha-1-antitrypsin is a relatively common genetic deficiency that results in early emphysema. The liver as the natural source of most alpha-1-antitrypsin synthesis was the target organ selected for gene replacement therapy studies. Previous work used recombinant retroviral vectors that encode the human alpha-1-antitrypsin cDNA for ex vivo and direct in vivo transduction of hepatocytes in dogs and rodents. This approach led to low levels of human protein in the serum of recipients. In this study, recombinant adenoviral vectors that express the human alpha-1-antitrypsin cDNA under the transcriptional control of the phosphoglycerate kinase (PGK) or RSV-LTR promoters have been constructed and used for the direct transduction of mouse hepatocytes in vivo. The animals transduced with the recombinant adenoviral vectors had therapeutic serum levels of human alpha-1-antitrypsin of up to 700 micrograms/mL. Thus, adenovirus-mediated gene transfer of the hAAT cDNA into the liver was able to produce therapeutic serum concentrations of protein.

Adenoviridae↗
PubMed1994

Attitudes of parents of young children to sperm donation--implications for donor recruitment.

An anonymous questionnaire was circulated to parents of young children to survey exposure to publicity about and attitudes to sperm donation (n = 192 couples; 50% response rate). Of those surveyed, 55% of men and women had seen or heard of the need for sperm donors; for 26% of couples, one or both partners had considered donation, and among half of those (13% of total) no objections to donating were raised. However, only two men had approached the clinic as donors. Objections to donation centred mainly on discomfort at having children outside their family, worry about future contact with donor insemination children, and worry about incest. Women were three times as likely to raise these objections as men. Of all respondents, 20% thought a donor should be used for only one recipient couple, while 50% suggested three or fewer families. Overall, 41% rated having non-identifying information about the recipient couple(s) as an important aspect of sperm donation, although only 9% of men and 17% of women considered personal contact important. While many people are aware of and receptive to the idea of being donors, very few act. Many would prefer that their spermatozoa were used for only one or a few couples about whom they had some information.

Adult↗
PubMed1983

Covalently closed circles of adenovirus 5 DNA.

The genome of adenoviruses is a double-stranded linear DNA molecule with inverted terminal repeats about 100 base pairs (bp) in length and a terminal protein covalently linked to the 5' nucleotide of each strand. Both of these features permit the formation of DNA circles, the inverted repeats allowing the circularization of single-stranded DNA and the terminal protein the joining of one or more molecules to yield double-stranded circles or concatemers. However, although the existence of covalently closed circles has been postulated, double-stranded viral DNA purified from virions or infected cells by conventional methods (that is, using proteases and phenol or chloroform) has always been obtained in a linear form. Here, we present evidence for the existence in adenovirus 5 (Ad5) infected cells of novel structures resulting from covalent head-to-tail joining of viral DNA molecules and show that these structures are due at least in part to the formation of covalently closed circles.

Adenoviridae↗
PubMed1976

The effect of freeze rate, duration of phase transition, and warming rate on survival of frozen canine kidneys.

The effect of cooling rate, warming rate, and duration of phase transition upon survival of frozen canine kidneys was investigated. In the present study, 11 kidneys out of 14 rapidly cooled (2--4degreesC/min) to --22degreesC and thawed (70--110degreesC/min) were viable following contralateral nephrectomy. The serum creatinine and BUN levels rose to a maximum of 8.4 and 30 mg%, respectively, on the eighth day post-contralateral nephrectomy. Average survival time was 10 days; however, two of the dogs in this group were allowed to survive, one for 3 months and one for over 2 years. Eight kidneys out of 16 slowly cooled (0.25-1.0degreesC/min) and either rapidly or slowly warmed (20-30degreesC/min) had function to produce small amounts of urine; however, they did not survive more than 5 days after contralateral nephrectomy. Cooling rates of 0.1 and 10degreesC/min were too harmful to the kidney to have renal function after reimplantation. The minimum renal cell damage as assessed by LDH and GOT in the post-freeze perfusate was found in the 2-4degreesC/min cooling rate following rapid warming (70degrees-110degreesC/min). Correlation of the duration of phase transition time to renal cell damage was linear for LDH and GOT (r=0.93). This result suggests that the duration of phase transition time also is an important factor during the freezing process, affecting post-thaw survival of canine kidneys.

Animals↗