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Biomedical subjects

H M Wallace

Publications and source records attributed to H M Wallace.

At least 73 records · Page 4Linked to original sources

Infant mortality in Sweden and Finland: implications for the United States.

Sweden had the lowest reported infant mortality rate (IMR) among countries of the world from 1920 until 1980. Since 1981, Sweden, Japan, and Finland have shared this number one ranking on a somewhat rotating basis. The United States ranks 18th. In 1985, the reported IMRs in Japan, Sweden, and Finland were 5.5, 6.8, and 6.3, respectively, while that of the United States was 10.6 per 1000 live births. This article presents detailed data on IMR in Sweden, Finland, and the United States. It also includes data on neonatal mortality, postneonatal mortality, age of death, and incidence of low birth-weight in the three countries. The paper briefly describes background information on maternal and infant care in Sweden and Finland, including prenatal care, labor and delivery, sex education, family planning, abortion, infant care, and social benefits in Sweden and Finland. The paper gives possible reasons for the achievement of the low IMR in Sweden and Finland, and considers the implications for the United States.

Birth Weight↗

Influence of cyclosporin A and alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, on two rodent T-cell cancers in vivo.

We have examined the influence of cyclosporin A (CsA), administered together with the polyamine antimetabolite, alpha-difluoromethylornithine (DFMO), on growth of the Roser acute T-cell leukaemia in PVG rats and on growth of the EL4 lymphoma in C57BL/6 mice. CsA or DFMO alone, administered from the time of tumour injection, markedly reduced numbers of circulating lymphoblasts in leukaemic rats, although survival was prolonged only in those animals given DFMO. Drug combination further reduced blood-borne tumour cells, but had no additional effects on tumour growth within organs or on host survival, compared to that achieved with DFMO treatment alone. Neither CsA nor DFMO, administered from the time of tumour-cell injection, nor both drugs in combination, affected peritoneal growth of the EL4 lymphoma or organ infiltration. Host survival was prolonged by DFMO. As anticipated, DFMO inhibited polyamine synthesis in vivo, but the observed anti-tumour effect of CsA was not accompanied by an alteration in polyamine biosynthesis. By reducing polyamine synthesis, however, DFMO may enhance the vulnerability of those malignant T cells which are susceptible to the as yet unexplained selective inhibitory action of CsA in vivo.

Animals↗

Teenage pregnancy in Sweden and Finland. Implications for the United States.

Fertility and the rates of pregnancy, live births, and abortion in teenagers in the United States are considerably higher than in most other developed countries of northern and western Europe. Fertility rates in teenagers in Sweden have declined significantly. The teaching of family life education is universal in Sweden and almost universal in Finland. Sex is openly discussed within society in both countries. Family planning and abortion services are geographically very available in both countries and both services and supplies are free. The educational level of both males and females is high in both countries. The United States has the opportunity to reduce teenage pregnancy by applying the experience of Sweden and Finland in the fields of family life education and family planning services.

Abortion, Therapeutic↗

Acetylation of spermidine and methylglyoxal bis(guanylhydrazone) in baby-hamster kidney cells (BHK-21/C13).

Treatment of BHK-21/C13 cells with methylglyoxal bis(guanylhydrazone) (MGBG) induced the cytosolic form of spermidine N1-acetyltransferase. It stabilized the enzyme against proteolytic degradation, but the drug did not affect the enzyme activity in vitro. MGBG was itself acetylated by BHK-21/C13 cells, but at only one-tenth the rate at which spermidine was acetylated. Acetylation occurred almost exclusively in the nuclear fraction. The product was identified as N-acetyl-MGBG by h.p.l.c., by using [3H]acetyl-CoA and [14C]MGBG as co-substrates. The results suggest that the acetylation of MGBG by BHK-21/C13 cells occurs by a different acetyltransferase enzyme from that which acetylates spermidine.

Acetylation↗

Factors affecting polyamine excretion from mammalian cells in culture. Inhibitors of polyamine biosynthesis.

Canavanine, diaminopropane, alpha-methylornithine and methylglyoxal bis(guanylhydrazone) decreased the intracellular polyamine concentrations in growing baby hamster kidney cells. Each of the inhibitors also prevented polyamine efflux into the extracellular medium. Concomitant with the decrease in polyamine excretion was a change in the distribution of polyamines in the extracellular medium. In each case there was a decrease in the amount of radioactivity present as free spermidine and an increase in that found as acetyl polyamines. The magnitude of this shift correlated with the degree of inhibition of excretion. It may be that acetyl polyamines play a role in the regulation of polyamine excretion.

Acetylation↗

Elevation of monoacetylated polyamines in human breast cancers.

Normal tissues contain only trace amounts of monoacetylated polyamines. N1-Acetylspermidine is present in high concentrations in mouse liver cells damaged by hepatotoxins and is also found in specialised cells of the hamster epididymis. In the present study human breast cancers were analysed for the presence of monoacetylated polyamines because N1-acetylspermidine is selectively elevated in human colorectal cancers. Free and monoacetylated polyamines (N1-acetylspermidine, N8-acetylspermidine and N1-acetylspermine), measured by high-performance liquid chromatography, were expressed as nmol/g wet wt of breast cancers (n = 54) or normal breast tissue (n = 15). Putrescine and monoacetylated polyamines were absent from normal breast tissue. Mean total content of monoacetylated polyamines in breast cancers 14.9 +/- 5.3 (S.E.) exceeded the mean total content of free polyamines (8.3 +/- 1.0) in normal breast tissue. Detectable levels of at least two of the monoacetylated polyamines were found in all breast cancers: N1-acetylspermidine was present in 51 (13.1 +/- 6.3), N8-acetylspermidine in 32 (0.6 +/- 0.1) and N1-acetylspermine in 28 tumours (1.2 +/- 0.3). There was no correlation between monoacetylated polyamine content of breast cancers and factors known to affect survival, i.e. tumour size, histological grade, oestrogen receptor status and node status. Monoacetylated polyamines are present in human breast cancers but not in normal breast tissue, implying that polyamine catabolism in breast cancers differs from that in normal breast tissue.

Breast Neoplasms↗

Activation of ADP-ribosyltransferase in polyamine-depleted mammalian cells.

Mammalian fibroblasts were cultured in the presence of alpha-methylornithine and/or methylglyoxal bis(guanylhydrazone), which inhibit the synthesis of polyamines. This led to a decrease in the cellular content of the polyamines spermine and spermidine by up to 60% when the cells were grown in the presence of both drugs together. The activity of the chromatin-associated enzyme ADP-ribosyltransferase was enhanced 2-3-fold in the drug-treated cells when measured in cells subsequently rendered permeable to exogenous NAD+, the substrate for the transferase. This is a novel and surprising observation, since the transferase is invariably activated by the addition of polyamines to a suitable incubation system such as permeabilized cells, isolated nuclei or the purified enzyme. We found no evidence that the activation was due to the appearance of DNA strand breaks, by using a variety of procedures including both neutral [the 'nucleoid' technique of Cook & Brazell [(1975) J. Cell Sci. 19, 261-279; (1976) J. Cell Sci. 22, 287-302]] and alkaline sucrose-gradient centrifugation and gel electrophoresis, suggesting that this therefore may not be the only means of regulating the activity of ADP-ribosyltransferase and that polyamines may have a role to play in this regard in vivo.

Adenosine Diphosphate Ribose↗