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Biomedical subjects

A Scott

Publications and source records attributed to A Scott.

At least 271 records · Page 15Linked to original sources

The preparation, characterization and application of monoclonal antibodies to human prostatic acid phosphatase (PAP).

Hybridoma cells secreting anti-PAP were produced by fusion of NS-1 myeloma cells with spleen cells from immunized Balb/c mice. Three of 32 hybrids secreted antibodies. Dilution cloning of the two hybrids producing the highest antibody titres showed that each antibody was monoclonal. One clone from each hybrid (clones ES2 and ES8) was selected for further study. The specificity of the antibodies appeared satisfactory, no inhibition of 125I-PAP binding to antibody being seen with extracts of bone, intestine, kidney, leucocytes, liver or lung. The association constants of the antibodies from ES2 and ES8 were 1.7 X 10(8) and 1.7 X 10(9) l/mol respectively, both were of the IgG1 class. For the immunoradiometric (IRMA) assay of serum PAP 125I-labelled monoclonal antibody was incubated with serum and the PAP-labelled antibody complex was separated by addition of solid-coupled polyclonal anti-PAP. The wide working range of the response curve (0.3-400 micrograms/l) and the rapid analysis time (4 h) offer practical advantages over RIA procedures. Clinical evaluation of the assay is in progress. ES8 antibody also appears to have good specificity for immunocytochemical applications. Localisation of micrometastases in bone in prostatic carcinoma was readily achieved.

Acid Phosphatase↗

Evaluation of monoclonal antibodies to blood group A.

Balb/c mice were immunized with human blood-group A2 active cyst fluid glycoprotein. Fusion of spleen cells with NS-1 myeloma cell line produced a total of 11 blood group antibody secreting hybridomas of which seven were apparently specific for blood-group A and were subjected to further evaluation. Of these 2 were IgM class and 5 IgG class. Two anti-A supernatants showed a significant decrease in avidity time against A2B cells when ionic strength was increased to 0.25. Tube titres of all anti-A supernatants were unaffected by ionic strength. pH had no effect on the avidity time or tube titre of any of the antibodies tested. The supernatant from one hybrid (ES-9) was selected for further evaluation as a blood grouping reagent. This supernatant had a tube titre of 1:128 and was used without concentration for comparison of its serological reactivity with two examples of commercial monoclonal anti-A and one example of human anti-A. Monoclonal anti-A (ES-9) was found to be a potentially useful red cell grouping reagent.

ABO Blood-Group System↗

A monoclonal antibody to human blood group B. Performance, evaluation and optimisation.

A monoclonal anti-B antibody (ES-4) was obtained by fusing spleen cells from a mouse immunized with soluble human blood group B substance with mouse myeloma cell line NS-1. The antibody was shown to agglutinate optimally group B cells at pH 7.2 and 0.15 ionic strength. Increasing the ionic strength to 0.24 gave optimal reactivity over a wider pH range. Culture supernatant containing anti-B (ES-4), after pH and ionic strength adjustment could be used in unconcentrated form as a red cell typing reagent. Anti-B (ES-4) agglutinated five examples of cells of the Bweak (Bw) phenotype and one example of acquired B phenotype. In contrast three of the Bw cells and the acquired B phenotype were not agglutinated by a commercial monoclonal anti-B by a tube technique. The data suggested that the equilibrium constant of the monoclonal anti-B (ES-4) was higher than that of the commercial reagent.

ABO Blood-Group System↗

A bovine papilloma virus vector with a dominant resistance marker replicates extrachromosomally in mouse and E. coli cells.

We describe the construction of a bovine papilloma virus-based vector (pCGBPV9) which contains a dominant selectable marker and replicates autonomously in both mouse and Escherichia coli cells. This vector contains the complete bovine papilloma virus genome, a ColE1 replication origin and a dominant selectable marker conferring resistance to kanamycin in bacteria and G418 in eukaryotic cells. A high number of G418R colonies are obtained after transfer of pCGBPV9 into mouse C127 cells. These G418R colonies contain vector DNA which replicates autonomously at approximately 10-30 copies per cell. The molecules are in most cases unrearranged and can be rescued into E. coli cells by bacterial transformation.

Animals↗

Small-for-dates babies at the age of four years: health, handicap and developmental status.

221 small-for-dates (SFD) and 244 average-for-dates (AFD) children were personally examined at birth, and seen thereafter at regular intervals up to 4 years, when a thorough assessment was made. There was an excess of SFD children with major congenital abnormalities; but no difference between the groups in the number of children who were handicapped without congenital abnormality. Their general health was good, and the prevalence of specific disease or major ill-health did not differ. SFD girls seemed to have less acute hearing than AFD girls; but there was not difference for boys. The prevalence of squint, impaired vision, speech defects, and abnormalities of gross and fine motor movements were equally low in both groups. At 4 years the mean scores for five sectors of development were significantly lower in the SFD than the AFD group. Within group analyses of 16 variables and their effects on developmental scores showed no associations in either group according to maternal height and weight, birthweights of previous siblings, the presence or not of hypertension and pre-eclampsia, bleeding during pregnancy, asphyxia and injury at birth, or birth order. Within each group the net effect of the remaining eight factors was assessed; adjustment being made for the other seven variables. In the SFD group social class and method of delivery made a significant contribution to total scores. In the AFD group significant differences were found according to social class, sex, gestational age at birth and smoking. Method of infant feeding just failed to achieve significance. When all the children were considered together, and birthweight group included as an additional variable, no significant differences remained between the SFD and AFD groups for any sector of development.

Breast Feeding↗

Large-for-dates babies at the age of four years: health, handicap and developmental status.

236 Average-for-dates (AFD) and 212 large-for-dates (LFD) children were personally examined at birth, and seen thereafter at regular intervals up to 4 yr, when a thorough assessment was made. No differences were found in the prevalence of handicap, health problems, speech and hearing defects, impaired vision or squint; and abnormalities of gross and fine-motor movements were equally low in both groups. At 4 yr the mean scores for five sectors of development were slightly higher in the LFD group, and the difference in total scores was significant; but when adjustment was made for sex and social class the difference became insignificant. Within group analyses of 16 variables and their effects on developmental scores showed no associations in either group according to maternal weight, height and siblings birthweight; hypertension, pre-eclampsia or bleeding during pregnancy; asphyxia or injury at birth. Within each group the net effect of eight factors was assessed; adjustment being made for the other seven variables. In the AFD group significant differences in total scores were found according to sex, social class, smoking, and method of infant feeding. In the LFD group social class and method of delivery made a significant contribution to total scores.

Analysis of Variance↗

A randomized placebo-controlled trial of ultraviolet light in the treatment of superficial pressure sores.

Ultraviolet (UV) light treatment of pressure sores enjoyed widespread popularity for many years, but recently its effectiveness has been increasingly questioned. Surprisingly, it appears that this form of treatment has never been tested by a randomized placebo-controlled trial. Eighteen patients residing in the Extended Care Unit of the Health Sciences Centre Hospital at the University of British Columbia and suffering from superficial pressure sores of recent onset were therefore randomly assigned to active and placebo treatment groups. Since treatment procedures appeared identical in both groups, both patients and hospital staff were blind as to individual allocation. Sixteen patients completed the study. Mean time to complete healing was 6.3 weeks in the UV treated group, significantly (P less than .02) less than the mean of 8.4 weeks in the placebo group. This difference persisted unchanged when each patient's age and the initial size of the sore were taken into account by an analysis of covariance. Thus, in spite of growing skepticism about its effectiveness, it appears that UV light may play a useful role in the treatment of pressure sores, and a systematic evaluation of different treatment protocols seems to be justified.

Aged↗

The relative contribution of different maternal factors in large-for-gestational-age pregnancies.

Relative and attributable risks were calculated to assess the potency of different maternal factors associated with large-for-gestational age (LGA) babies in individuals and in the population as a whole. In multiparous women the most important factor was the fast fetal growth rate demonstrated in previous pregnancies. Non-smoking also made a large contribution to the LGA population (43.65%) and the risk to individual patients was doubled. The relative risk for height steadily rose with increasing stature, but the effect was much more marked for weight. Heavy women made a considerable contribution to the LGA population (26%) and the effect of increasing weight is such that very heavy women (more than +2 SD) are nine times more likely to have an LGA baby than those of average weight. The relative risk also rose sharply with increasing parity. Nevertheless, 27.5% women in our LGA group were having their first baby. The possibility that a very obese non-smoking primiparous woman may be bearing a very large baby should not be overlooked.

Birth Weight↗

Cytotoxic activity of peripheral blood and cerebrospinal fluid lymphocytes from patients with multiple sclerosis and other neurological diseases. Analysis at the single cell level using morphological and surface marker phenotype criteria.

The large granular lymphocyte (LGL) has been identified in normal individuals' MNC population as the NK-K cell (Ault and Weiner 1978; Timonen et al. 1981); it bears the OKM1 surface antigen (Breard et al. 1981; Fast et al. 1981) and while negative for T cell antigens OKT4 and OKT8, is a low avidity E-rosette forming cell. However, in a unfractionated nylon wool passed peripheral blood lymphocyte (NWP PBL) population, we show that not more than 50% of KN activity in normal or OND control NWP PBL and 30% NK activity in MS NWP PBL can be attributed to this cell. Nevertheless, 100% of control K cell activity and 50% of MS K cell activity can be mediated by an LGL. MS patients have normal proportions of LGLs in their NWP PBL. The proportion of LGLs in CSF of MS and OND patients is too low to account for the number of CSF K cells. While in control NWP PBLs, the LGLs are OKM1+ and mediate NK and ADCC, in MS the LGL NK effectors are probably different from LGL-K cell effectors. In MS both populations include effector cells with cell surface antigens. Thus, the OKM1+ LGL characteristics may not be used in analysis of NK and K cells in multiple sclerosis.

Acute Disease↗

Growth in the first four years: I. The relative effects of gender and weight for gestational age at birth.

The growth of 238 small-for-dates (SFD), 246 average-for-dates (AFD) and 241 large-for-dates (LFD) babies was assessed at regular intervals from birth to four years. At all ages, and for both sexes, the mean weight, length or height, and head circumference values for the two extreme groups differed significantly from the AFD group (P less than 0.001). During the first six months actual and relative growth was highest in the SFD group and lowest in the LFD group. With the exception of length in the LFD group it was higher for boys than for girls. Thereafter differences in actual values were slight, while the proportional increases for the three groups were almost identical. Differences from the AFD mixed-sex mean value were plotted for each group and sex combination. Stabilization of the mean trajectories in the two extreme groups occurred at six months for weight and head circumference, but not until 12 months for length. For each child a straight line was fitted on a log scale to these differences from six months (12 months for length) to four years, and analyses of variance of the slopes and intercepts obtained. The sex difference for weight and height gradually decreased, but for head circumference held constant. Estimates of the difference in intercepts of the birthweight groups and sexes showed that within the LFD group the difference in height between boys and girls was much less than in the other two groups. The sex difference for head circumference was slightly larger than the difference between SFD and AFD groups, and twice the difference between the LFD and AFD groups. At the age of four years the mean value for AFD boys was higher than LFD girls (P less than 0.01), and those for SFD boys and AFD girls were almost identical.

Birth Weight↗

Growth in the first four years: II. Diversity within groups of small-for-dates and large-for-dates babies.

238 small-for-dates (SFD), 246 average-for-dates (AFD) and 241 large-for-dates (LFD) infants were personally examined at birth, and measured thereafter in their own homes at the ages of 2, 6, 12 and 18 months, 2, 3 and 4 years. At each age weight, length or height, and head circumference measures in the SFD and LFD groups were distributed around the appropriate sex AFD mean values. In both extreme groups major shifts towards the mean occurred in the first six months for all three measures. From one year onwards only small within group fluctuations were seen. Correlations between one and four year values for weight, height and head circumference were high. At four years about 50% SFD children were within 1 S.D. of the mean, and 10% were still very small. Slightly more LFD children (55-60%) were near to the mean at this age, particularly for their head circumference values (70%), and only about 8% LFD children had very large heads. Trajectories of individual SFD and LFD children illustrate the great diversity of growth patterns within and between groups.

Birth Weight↗

Growth in the first four years: III. The effects of maternal factors associated with small-for-dates and large-for-dates pregnancies.

Relationships between maternal factors associated with very slow and very fast fetal growth rate, and the postnatal growth patterns within groups of 238 small-for-dates (SFD) and 241 large-for-dates (LFD) children were examined. Within the SFD group significant differences were found in their weight, height, and to a lesser extent head circumference, according to maternal weight, height, parity, social class, and the birthweights of previous siblings. In the LFD group no differences were found according to maternal weight or the birthweights of previous siblings. Maternal height affected only weight and height; first-born were heavier, and children in the upper social classes had larger heads than the rest. After adjustment for sex, the proportion of the variance in size between one and four years accounted for by all these factors was: SFD group 16% for weight and height, and 10% for head circumference; LFD group 6% for all three measures.

Adult↗

Growth in the first four years: IV. Correlations with parental measures in small-for-dates and large-for-dates babies.

Parent-child correlations for weight, height and head circumference on eight occasions between birth and 4 years were estimated within groups of 212 small-for-dates (SFD), 208 average-for-dates (AFD) and 221 large-for-dates (LFD) children. For mothers and fathers in the SFD and AFD groups, and fathers in the LFD group, correlations for weight were generally low in the first year, with moderate increases up to 4 years. No correlations for weight at any age were found between mothers and LFD children. There was a gradual rise in correlations for length in all three groups for both mothers and fathers between birth and 4 years. Head circumference correlations in the AFD and LFD groups were relatively high at birth and showed little change thereafter. Mother-child correlations for head circumference in the SFD group were absent at birth, but then rose sharply to a value comparable with the AFD parents' correlations at 18 months, with the little change thereafter. No SFD father-child correlations for head circumference were found at any age. Children's standards of weight and head circumference adjusted for mid-parental measures would, in some cases, be misleading.

Adult↗

Social class and birthweight: a new look.

The effects of social class on birthweight, and its interactions with other maternal factors, were examined in groups of women bearing small-for-dates (SFD), average-for-dates (AFD) and large-for-dates (LFD) babies. The relative risk of a lower social class woman having an SFD baby steadily decreased from 1.75 to 1.20 as adjustment was cumulatively made for smoking, hypertension, maternal age and height. The subsequent addition of weight and weight-for-height made little change. The unadjusted risk of a lower social class woman having a LFD baby was very close to unity (0.99). Adjustment for other maternal factors, in the same order as at the other extreme, showed a steady rise to a significant level (1.45) when height was included; but there was a sharp reversal to a non-significant risk of 1.12 when weight was added. The large contribution of obesity in the lower classes seems to counterbalance those for height, age and smoking in the upper classes in the LFD group. The interactional effects of other maternal factors and social class are not operating to an equal and opposite degree at the two extremes of the birthweight range.

Birth Weight↗