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Biomedical subjects

J Todd

Publications and source records attributed to J Todd.

At least 145 records · Page 8Linked to original sources
PubMed1988

Attachment of human placental-type alkaline phosphatase via phosphatidylinositol to syncytiotrophoblast and tumour cell plasma membranes.

Phosphatidylinositol anchors human placental-type alkaline phosphatase (PLAP) to both syncytiotrophoblast and tumour cell plasma membranes. PLAP activity was released from isolated human placental syncytiotrophoblast plasma membranes and the surface of tumour cells with a phospholipase C from Bacillus cereus. This was a specific event, not the result of proteolysis or membrane perturbation, but the action of a phosphatidylinositol-specific phospholipase C in the preparation. Soluble PLAP, released with B. cereus phospholipase C and purified by immunoaffinity chromatography, ran on SDS-PAGE as a 66-kDa band. This corresponded to intact PLAP molecules. The protease bromelain cleaved lower-molecular-mass PLAP (64 kDa) from the membranes. Flow cytometry demonstrated that B. cereus phospholipase C released human tumour cell membrane PLAP in preference to other cell-surface molecules. This was in contrast to the non-specific proteolytic action of bromelain or Clostridium perfringens phospholipase C, which had no effect on membrane PLAP expression. Radiolabelling of tumour cells with fatty acids indicated PLAP to be labelled with both [3H]myristic and [3H]palmitic acid. This fatty-acid--PLAP bond was sensitive to pH 10 hydroxylamine treatment indicating an O-ester linkage.

Alkaline Phosphatase↗
PubMed1987

Quantitative assessment of infant reaching movements.

We have identified a fundamental property of human motor behavior as a tight coupling of the curvature-speed relationship in the reaching movements of 5- to 9-month-old infants. This relationship termed a movement unit, occurs regardless of the distance of duration of the reach and in spite of the developmental change that occurs in grasping during this period. Movement unit durations are tightly clustered around 200 ms regardless of overall duration or distance or the position of the unit in the reach. The curvature-speed coupling has been identified by others in adult reaching and handwriting. Models of biological motor control must account for this invariant relationship.

Journal Article↗
PubMed1987

Children with the fragile X chromosome at schools for the mildly mentally retarded.

An investigation of children in schools for the moderately mentally handicapped in Coventry demonstrated that 29 of 259 children had a significant chromosomal abnormality. 10 of 155 boys (6 per cent) and 10 of 104 girls (10 per cent) had the fragile X syndrome. The clinical features which suggested this syndrome in males were IQ in the 50 to 70 range, head circumference greater than the 50th centile and post-pubertal testicular volume greater than the 50th centile. For both males and females, large ears were a useful sign. All children with fragile X had a carrier parent. The occurrence of mental retardation among sibs was one in two for brothers and one in four sisters. Considering all the males with fragile X syndrome resident in Coventry (this and previous studies), there were twice as many in schools for the moderately mentally handicapped as there were in schools for the severely mentally handicapped. There were as many females as males in the schools for the moderately mentally handicapped.

Cephalometry↗
PubMed1987

Augmented antitumor effect of combined human natural interferon-alpha and mismatched double-stranded RNA treatment against a human malignant melanoma xenograft.

The antitumor effect of combined natural human interferon-alpha (IFN) and mismatched double-stranded RNA (dsRNA) treatment against the human malignant melanoma cell line, BRO, was studied. In vitro results, using a tissue culture antiproliferative assay, indicated that these cells were moderately sensitive to IFN-alpha. In contrast, mismatched dsRNA had no antitumor effect, and a minimal stimulation of cell growth, over part of the concentration range tested, was observed. Mismatched dsRNA did not potentiate the antitumor effect of IFN-alpha in cells receiving combination treatment. Xenografts of BRO cells, inoculated subcutaneously into nude mice, were used to evaluate the antitumor effects of IFN-alpha and mismatched dsRNA. Growth of the primary tumor was inhibited by both drugs alone or in combination (p less than 0.001), but the combined treatment was most effective and appeared to be additive. The number of spontaneous lung metastases was also inhibited (p less than 0.02) in all treatment groups. Survival, however, was significantly increased only in the IFN-alpha/mismatched dsRNA group (p less than 0.02 compared to controls, p less than 0.05 compared to mismatched dsRNA alone). Determination of splenic natural killer (NK) cell activity against BRO cells demonstrated that significantly augmented NK activity to the same extent, but that the IFN-alpha alone had no effect. These results indicate that IFN-alpha worked through direct antiproliferative mechanisms while mismatched dsRNA stimulated host immunomodulatory effects. The increased tumor growth inhibition and survival in the dual treatment group appears to result from the combined direct antiproliferative and indirect immunomodulatory effects.

Animals↗
PubMed1986

The frequency of the fragile X chromosome among schoolchildren in Coventry.

A population study has been carried out among schoolchildren in the City of Coventry in order to ascertain the frequency of mental retardation associated with the fragile X chromosome. The prevalence of the fragile X mental retardation syndrome in the 11 to 16 year age group (the age of greatest ascertainment) was about 1.0 per 1,000 and therefore indicates that the syndrome is a major cause of mental retardation.

Adolescent↗
PubMed1986

Twelve families with fragile X(q27).

Through a community study of boys requiring special education for the severely mentally retarded, 12 families were ascertained in which the fragile X was found to be segregating. By assiduous follow up of these families, it was found that in only four of them could male transmission be ruled out from the grandparents' or great grandparents' generation and that the segregation ratios are disturbed.

Cells, Cultured↗
PubMed1985

Is it possible to make a clinical diagnosis of the fragile X syndrome in a boy?

Clinical observations were made on a series of 156 boys with severe mental retardation, before cytogenetic results were known. The clinical features that helped to distinguish the 14 boys with the fragile X chromosome from those without were: head circumference over the 50th centile, postpubertal testicular volume over the 50th centile, and an IQ between 35 and 70. If the above clinical features were all present, then the chance of finding the fragile X chromosome was 1 in 3.6, whereas the chance of finding this abnormality in any boy with severe idiopathic mental retardation, regardless of his clinical features, was 1 in 9. Two boys with fragile X syndrome did not, however, possess any of the above clinical features. Moreover, some of the other retarded boys had clinical features of the syndrome, or an X linked pedigree, but lacked the chromosome abnormality.

Birth Weight↗
PubMed1985

A community study of severe mental retardation in the West Midlands and the importance of the fragile X chromosome in its aetiology.

This paper describes a community based study of 156 boys with idiopathic, severe mental retardation. The boys were examined and a pedigree taken before the cytogenetic results were known. The prevalence of the fragile X chromosome among this group of boys was high: 9% in the whole group and 11% after 39 boys with specific features had been excluded. The fragile X syndrome is therefore an important cause of idiopathic, severe retardation. Its clinical features of large head, large testes, and IQ in the 35 to 70 range were often but not always present in the 14 boys identified in this study. In the whole group, the recurrence of severe mental subnormality was high: 1 in 8 for brothers and 1 in 25 for sisters. This high recurrence was partly due to the fragile X syndrome, partly to X linked mental retardation not accompanied by cytogenetic abnormalities, and partly due to autosomal recessive disease. Autosomal recessive disease was perhaps higher in the West Midlands than elsewhere (such as British Columbia, for example 1) because of the disproportionate contribution by Asian immigrants.

Adolescent↗
PubMed1983

Inhibition by estradiol of the lactogenic effect of prolactin in primate mammary tissue: reversal by antiestrogens LY 156758 and tamoxifen.

Increasing concentrations of estradiol (E2) ranging from 0.01 to 10 nM were found to inhibit partially but significantly the lactogenic effect of ovine prolactin (oPRL) on alpha-lactalbumin production in primate mammary tissues maintained in organ culture for 9 days. E2 at 10 nM inhibited by 38% (mean) PRL-stimulated alpha-lactalbumin production measured by radioimmunoassay. E2 antagonized the effect of oPRL by reducing new alpha-lactalbumin synthesis as determined by specific immunoprecipitation of alpha-lactalbumin and by analysis with NaDodSO4 gel electrophoresis. In immunoprecipitation studies, the mean inhibition of alpha-lactalbumin production was 57.6%. E2 in the absence of oPRL had no effect on alpha-lactalbumin production. In contrast to previous observations in rodents, progesterone was found to be a much weaker inhibitor of PRL-induced alpha-lactalbumin production than was E2 in primate breast tissues. Mean inhibition of oPRL-stimulated alpha-lactalbumin production was 32.3% with 10 microM progesterone and 8.3% with 10 nM. The inhibitory effect of E2 on oPRL-stimulated alpha-lactalbumin production was significantly reversed by both tamoxifen and a new antiestrogen, LY 156758. Although exact comparison of the effects of these two antiestrogens was not possible, it was apparent that LY 156758 was more potent in blocking the E2 inhibitory effect. In summary, these studies provide evidence that physiologic concentrations of estradiol partially block the lactogenic effect of PRL in primate mammary glands, suggesting a new role for estrogen in mammary physiology. The inhibitory effect of estrogen treatment on milk production in women after parturition may possibly be explained by this direct antagonism between E2 and PRL.

Animals↗
PubMed1982

Estradiol inhibits prolactin induced alpha-lactalbumin production in normal primate mammary tissue in vitro.

The effect of estradiol on prolactin induced alpha-lactalbumin production in normal primate mammary tissue was studied by maintaining tissues in organ culture with or without various combinations of oPRL and 17 beta-estradiol. As expected alpha-lactalbumin was increased byoPRL. 17 Beta-estradiol was found to have a significant inhibitory effect on oPRL-induced alpha-lactalbumin production. By 9 days in culture estradiol (10(-11) M) caused a mean 31% inhibition of prolactin-induced alpha-lactalbumin; with estradiol (10(-8) M) the inhibition was 40%. In the absence of oPRL, estradiol did not inhibit alpha-lactalbumin production. Thus it appears that estradiol directly antagonizes the lactogenic effect of prolactin on the normal primate mammary gland.

Animals↗
PubMed1981

The syndrome of Capgras.

Three new cases of the syndrome of Capgras are presented. An unusual variant of the syndrome is recorded. It is contended that the definition of the syndrome should be widened to include impersonators who exhibit slight differences from the prototype, and that ambivalence and projection cannot explain all cases. The syndrome is critically reviewed.

Adult↗
PubMed1980

Pergolide mesylate: a potent day-long inhibitor of prolactin in rhesus monkeys and patients with Parkinson's disease.

The effect of a new synthetic ergot alkaloid, pergolide mesylate, on the inhibition of PRL during 24-h periods was evaluated in four rhesus monkeys and three patients with Parkinson's disease. In the monkeys, the mean PRL level during the 24-h period fell to 24% of control in response to 50 micrograms. With 1000 micrograms pergolide daily and to 6.6% of control with 200 micrograms pergolide daily, PRL was unmeasurable in the great majority of samples over 24 h. In addition, the marked episodic fluctuation in PRL occurring in controls was not observed in treated animals. In three patients with Parkinson's disease, treatment with pergolide also resulted in uniform 24-h suppression of PRL. In one patient on pergolide (100 micrograms/day), the mean 24-h PRL level fell to 18% of control, and in two other patients on 200 and 600 micrograms pergolide, respectively, whose mean PRL levels were 4.1 and 7.4 ng/ml, respectively, before treatment, no PRL was detected in any of the blood samples obtained during the 24-h periods. These data provide evidence that pergolide is a potent inhibitor of PRL in rhesus monkeys and in patients with Parkinson's disease; the effect is iniform over 24-h periods.

Animals↗
PubMed1980

Evidence that human growth hormone is a potent lactogen in primates.

To help determine if human GH (hGH) plays a physiological role in normal mammary function or diseases of the human breast, a study was undertaken to examine the lactogenic potency of hGH in a subhuman primate system. hGH was previously considered a relatively weak lactogen when tested in avian crop sac and rodent mammary assays. The effect of hGH on the production of alpha-lactalbumin in organ cultures of primate mammary tissue was compared with the effect of equal concentrations of ovine PRL (oPRL). Mammary tissues from seven adult rhesus monkeys were maintained in culture for 9 days (medium changed every 3 days) without and with oPRL or hGH in doses ranging from 30-1000 ng/ml. hGH was consistently more effective than oPRL in the stimulation of alpha-lactalbumin production in over 90% of the cases. For example, mean (+/- SEM) alpha-lactalbumin production at the 6-day time period in response to 1000 ng/ml hormone was 12.9 +/- 3.3 ng/ml for oPRL and 61.9 +/- 18 ng/ml for hGH. Overall, it was calculated that hGH had 328% the potency of oPRL in adult rhesus monkey mammary tissue. In pigtail macaques, hGH was also a more potent stimulant of alpha-lactalbumin production than oPRL, but the differences wer not as great as in rhesus monkeys. alpha-Lactalbumin in medium was higher in hGH-containing dishes than in those containing oPRL in over 85% of the cases. It was calculated that the lactogenic potency of hGH in macaque tissue was 160.5% that of oPRL. The differences between species were significant. These results indicate that hGH is a more effective lactogen in subhuman primates than oPRL and suggest the possibility of GH may be a lactogen which has physiological importance.

Animals↗