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Biomedical subjects

I M Lewis

Publications and source records attributed to I M Lewis.

14 recordsLinked to original sources
PubMed2003

Prospective study of factors influencing the persistence of symptoms in hospitalised patients with acute infection.

Sequential patients, aged 18-50, admitted to an Infectious Diseases Unit of a large teaching hospital with an acute infection, completed validated psychometric questionnaires on admission and were followed up at three monthly intervals for 12 months. 34% of patients available for follow-up remained symptomatic at 3 months, but by 6 months and for the rest of the study, only about 20% of patients available for follow-up remained symptomatic. Symptoms resembled those of the initial infection at 3 months, but for the remainder of the study, most patients complained of nonspecific symptoms of tiredness and lassitude. Patients symptomatic at 3 and 6 months (S+) had significantly higher depression scores on admission compared with nonsymptomatic group (S-) (P<.05). Stepwise logistic regression revealed that case level depression on admission was predictive of a 13-fold increase in the chance of remaining symptomatic at 6 months. These associations were lost by 12 months. In conclusion, this study has supported the hypothesis that psychopathology occurring at the time of an acute infection can lead to persistent symptoms that at least in the short term resemble those of the acute illness. This relationship breaks down after 6 months, when symptoms become less specific and may be conditioned by exhausting and distressing social situations other than acute illness.

Acute Disease↗
PubMed2001

Development of bovine embryo-derived clones after increasing rounds of nuclear recycling.

This study assessed in vitro and in vivo developmental ability of bovine embryo-derived clones after one, four or seven rounds of nuclear transfer. Initial donor embryo production and all subsequent cultures were performed in vitro. Donor clonal embryo lines were vitrified and warmed either once (first generation), twice (third generation) or three times (sixth generation) before the final round of cloning. No differences were observed in fusion, cleavage and development rates to the 16-cell stage between the first six cloning generations. Likewise, neither the fusion nor cleavage rates were different between first, fourth and seventh generation clones. However, development to morulae and blastocysts decreased significantly as the number of recycling rounds increased (24.8, 15.1 and 13.6% for first, fourth and seventh generation, respectively). In addition, the proportion of blastocysts compared to morulae decreased, indicating slower developmental speed in later generation clones. After transfer of 16, 25 and 7 clones to 7, 11 and 2 recipients (first, fourth and seventh generation, respectively) initial pregnancy rates of 57, 27 and 0% were obtained. Final rates of calves to term were 25 and 4% per transferred clone for first and fourth generation clones, respectively. These results indicate greatly reduced in vitro and in vivo developmental capacity of bovine embryo-derived clones after several rounds of nuclear recycling. Whether it is caused by intrinsic factors associated with the genome modification and reprogramming as such, or by external factors such as prolonged in vitro culture period or the effects of vitrification, remains to be determined.

Animals↗
PubMed2001

Determining the immune mechanisms of protection from AIDS: correlates of immunity and the development of syngeneic macaques.

The AIDS pandemic is a global emergency and a preventive vaccine is urgently needed. CD4 and CD8 T-cell responses appear important in controlling human immunodeficiency virus (HIV)-1 in humans and simian immunodeficiency virus (SIV) in macaques. The utility of vaccines that induce high levels of SIV- or HIV-specific T cells has recently become clearer. Since T cells recognize virus-infected cells rather than free virus, T-cell-based vaccines only have the capacity to control infections (non-sterilizing immunity) and to prevent continuing or persisting infection. An HIV/SIV infection of macaques that is partially controlled by vaccine-induced T-cell responses permits a critical window of opportunity for the efficient generation and recruitment of additional T- and B-cell immune responses to the incoming viral inoculum. Although CD8-depletion experiments in macaques have defined the utility of CD8 T responses in control of SIV infections in macaques, direct evidence on the utility of either CD4 or CD8 T-cell responses in protective immunity to SIV following vaccination is lacking. The availability of genetically identical macaques would allow cell transfer studies and help define with more certainty the role of cellular immune responses in protection from AIDS. The review also focuses on the development of syngeneic macaques by twinning and cloning technologies.

AIDS Vaccines↗
PubMed2001

Somatic cell cloning without micromanipulators.

Until now, micromanipulators have been regarded as indispensable for somatic cell nuclear transfer. This paper describes an improved zona-free nuclear transfer procedure with manual bisection of oocytes, selection of cytoplasts by Hoechst staining, and two-step fusion of somatic cells from primary granulosa cell cultures with two cytoplasts. Blastocyst rates in the three systems tested for zona-free embryo culture were 0%, 18%, and 36% for microdrops, well of the wells (WOW system), and microcapillaries (GO system), respectively. This simple, rapid, and inexpensive procedure may become a useful alternative to the existing techniques for somatic cell nuclear transfer for large-scale application of the technology.

Animals↗
PubMed1998

The effect of recipient oocyte volume on nuclear transfer in cattle.

This study compared the developmental potential of bovine nuclear transfer embryos with varying amounts of cytoplasm. Embryos formed from single cytoplasts fused to blastomeres by a single electrical pulse or from double cytoplasts using a double electrical pulse resulted in reconstituted embryos containing 75% and 150% of the original oocyte volume. No differences in fusion, cleavage, or development rates to blastocysts were observed between the groups. Mean cell numbers 2 days after fusion were significantly lower in single-cytoplast clones. Cell numbers of resulting blastocysts were likewise significantly lower in single-cytoplast clones. Embryos formed by fusion of blastomeres with single cytoplasts using a single electrical pulse or from double cytoplasts using either a single or a double pulse resulted in reconstituted embryos containing 50%, 100% and 100% of the original oocyte volume. Again, no differences in fusion or cleavage rates were observed between groups, but the development to blastocysts at day 7 was significantly higher in double cytoplasts constructed with one fusion pulse than in single cytoplasts (P < 0.05). Mean cell numbers 2 days after fusion were significantly lower in single-cytoplast clones (P < 0.05), but at the blastocyst stage, no statistically significant differences in cell numbers were observed. The results of this study show that cytoplasmic volume plays a role in the development of nuclear transfer embryos. When using crude enucleation methods such as oocyte bisection, normal cytoplasmic volumes can be achieved by fusing double cytoplasts with embryonic blastomeres.

Animals↗
PubMed1998

Genetically identical primate modelling systems for HIV vaccines.

There is an urgent need for a safe and effective vaccine to prevent human immunodeficiency virus (HIV) infection. Several HIV vaccine candidates have shown promise, but many concerns regarding the safety and efficacy of current vaccines remain. A major hindrance in HIV vaccine development is a poor understanding of precisely what functions HIV vaccines are required to perform in order to protect humans from HIV-1. Only higher primates (i.e. macaques, chimpanzees and humans) are susceptible to HIV-1 or the closely related virus 'simian immunodeficiency virus'. These species are outbred and there are remarkable genetic differences in both the immune responses to vaccines and their susceptibility to infection. The development of genetically identical macaques would be a major step towards dissecting what immune responses are required to protect from HIV infection. For example, live attenuated HIV-1 vaccines are likely to be highly efficacious, but will induce disease in a substantial proportion of recipients. Defining why a live attenuated vaccine is effective should allow safer vaccines to be developed, retaining only the immunologic properties of an effective vaccine. The reduction in 'background genetic noise' obtained by studying genetically identical primates would provide concise answers to critical HIV vaccine issues, by studying a minimal number of animals. Such an approach could potentially be employed in other diseases where non-human primates are the only available model. Small studies can be performed where identical twins are generated by embryo bisection; however, larger studies where multiple immune parameters are simultaneously evaluated would be facilitated by cloning technology. Despite the technical difficulties to be overcome, the potential gains in human health from the development of genetically identical non-human primates are worthy of careful consideration.

AIDS Vaccines↗
PubMed1998

Large-scale applications of cloning technologies for agriculture: an industry perspective.

The present costs and efficiencies of producing cloned embryos, pregnancies and offspring using the simplified nuclear transfer techniques developed in the authors' laboratories are compared with those required for the large-scale application of such cloning technologies in cattle. The current costs in the laboratory of producing large numbers of genetically identical cloned embryos for transfer is around $15.00 per blastocyst, which is within the cost estimated to be commercially viable for cloned female dairy embryos for transfer. However, the pregnancy and calving rates from the transfer of such embryos are still well below that required for large-scale commercial application for which ongoing pregnancy rates of at least 50% per recipient will be required. The current pregnancy rate (30-40 days post-transfer) following the transfer of an average of three cloned embryos per recipient is 37%, and the calving rate 17%, representing high losses between pregnancy diagnosis and term. In the beef industry and in some dairy situations the final product (cloned bulls for natural mating) will have a much higher inherent value and different parameters will therefore apply. Recent developments in the technologies that are likely to increase the probabilities of large-scale application are discussed, including recycling nuclear transfer embryos, somatic cell cloning, new cryopreservation techniques and automated oocyte harvesting.

Animals↗
PubMed1977

A clotting defect in an Arab colt foal.

A multiple clotting defect in a 3 month old Arab colt foal associated with a deficiency in Factors VIII, IX, and XI is described. No abnormalities in clotting factors were detected in the colt's sire, dam, half-sister and half-brother.

Animals↗
PubMed1975

The distribution of delta5-3beta-hydroxysteroid dehydrogenase in the graafian follicle of the mare.

Graafian follicles of various sizes obtained from mares at different stages of the oestrous cycle were examined histologically and histochemically for delta5-3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity and related enzymes. The 3beta-HSD activity was not found in the theca interna of any follicles but was present in the membrana granulosa of well-vascularized large follicles in the late luteal phase of the cycle and at oestrus. These findings indicate that pregnenolone cannot be converted into progesterone in the theca interna. It is suggested that this conversion occurs in the membrana granulosa and that progesterone then passes into the theca interna where it is converted into oestrogen. Participation of both granulosa and thecal cells in oestrogen production is also discussed from a morphological view-point.

Animals↗
PubMed1975

Physiological variations in levels of 2,3-diphosphoglycerate in horse erythrocytes.

The levels of 2,3-diphosphoglycerate (2,3-DPG), which affects the transport of oxygen by haemoglobin, were examined in horse blood. Resting levels of erythrocyte 2,3-DPG were established in thoroughbred horses, and levels of 2,3-DPG together with haemoglobin levels, were examined in a variety of conditions. A negative correlation was observed between erythrocyte 2,3-DPG and haemoglobin levels. Mares had higher erythrocyte 2,3-DPG levels was observed during training, and this variation may have a significant effect on haemoglobin oxygen transport. Erythrocyte 2,3-DPG levels were not affected by age or exercise.

Age Factors↗
PubMed1975

Oxygen affinity responses to 2,3-diphosphoglycerate, and methaemoglobin formation in horse and human haemoglobins.

The oxygen affinities of horse and human haemoglobins were compared in the absence and presence of the allosteric effector 2,3-diphosphoglycerate (2,3-DPG). Horse haemoglobin solutions showed significantly smaller responses to the presence of 2,3-DPG, and this difference may be due to different amino acid substitutions at position NA2(2)beta. Horse haemoglobin solutions from erythrocytes containing different ratios of the two different haemoglobin types showed similar oxygen affinities in the absence and presence of 2,3-DPG. Horse haemoglobins in solution were found to autoxidise to methaemoglobin much more readily than human haemoglobin under the same conditions, and this is an important consideration when measuring the oxygen affinity of horse haemoglobin solutions. This difference could be due to different amino acid residues at position NA2(2)beta.

Animals↗