Biomedical subjects
Publications and source records attributed to N A Nelson.
The 2-(aminomethyl)-2-decarboxy analogs of prostaglandin F2 alpha (PGF2 alpha), (15S)-15-methyl-PGF2 alpha, 16-phenoxy-omega-tetranor-PGF2 alpha and 16,16-dimethyl-PGF2 alpha were synthesized. The amino analogs closely resemble the parent PGF2 alpha compounds as antifertility agents in the hamster.
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This paper reports the synthesis of 11-dehydrothromboxane B2 methyl ester (II), 15-dehydrothromboxane B2 methyl ester (III), 15-dehydro-13, 14-dihydrothromboxane B2 (XII) and 2,3-dinorthromboxane B2 methyl ester (XV). These compounds, as their free acids, have been reported to be thromboxane metabolites.
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A double-blind study of 62 normal women was carried out to determine if there was any correlation between the mean score of six weekly leucocyte-migration-inhibition tests (L.M.T.) against breast-cancer antigen, xeromammographic findings, and the presence of other epidemiological risk factors for the development of breast cancer. 36 women had abnormal mammograms, and 11 of these 26 (30.5%) had a mean L.M.T. score greater than or equal to 10%. 26 women had normal mammograms, and only 1 of these (3.8%) had a mean value greater than or equal to 10%. This difference was significant (p less than 0.02). A family history of breast cancer and/or previous surgery for cystic and proliferative disease also correlated significantly with L.M.T. score (p less than 0.05); the combined presence of epidemiological risk factors and an abnormal mammogram correlated most strongly with L.M.T. score (p less than 0.01). Although the results may indicate an "immunological risk factor" towards the development of breast cancer, the biological relevance of this observation remains to be proven.
In a cohort of 23,146 pregnant females followed for 37-56 months subsequent to collection of prenatal sera, 57 cases of carcinoma of the cervix were encountered. Three controls were selected for each case from the residual cohort matched to cases for age, residence, number of prior cytology smears taken, and the data of entry to the study. The antibody activity to herpesvirus type 1 and type 2 was examined by the indirect hemagglutination test. The proportion of cases positive for HSV-2 infection was greater than that of the controls; however, the difference was not significant at the 5% level. The relative risk value for the association between HSV-2 infection and carcinoma of the cervix was found to be 2.33. The geometric mean titers of IHAT revealed that the cases of cervical cancer had a higher titer than the controls with respect to HSV-1 as well as HSV-2 antibodies. A sufficiently longer follow-up, yielding a larger sample size, is desired to assess the specific role of HSV-2 infection in development of cervical anaplasia.
In an attempt to describe epidemiologic features to generate etiological hypotheses and to study natural history, 121 cases of childhood CNS neoplasms under 15 years of age, occurring during 1950-66 in Manitoba, were analyzed. The incidence of CNS neoplasms in childhood (2.4/100 000 per annum) ranks second only to leukemia in Manitoba. For both sexes somewhat elevated incidences were noted for both extreme age groups; i.e. 0-4 and 10-14. Such peaks were more prominent for gliomas, which may indicate differential factors operation in the genesis of gliomas between early and late childhood. The former may be related to genetic and/or perinatal environmental factors and the latter, to environmental factors, in early childhood. Excess occurrences of gliomas among Irish, Scottish and Icelandic offsprings were observed, which possibly indicates the importance of either genetic or environmental factors peculiar to these ethnic groups. There was no evidence of time clustering (i.e. season and year) by estimated conception or by birth. Further investigation into the relative role of genetic and environmental factor in the genesis of childhood gliomas are in order.
The relative binding affinities for both the prostaglandin (PG)E1 and PGF2alpha specific bovine luteal binding sites were determined for five PGE and fourteen PGF derivatives and analogs. Relative binding affinity was determined in vitro using membranes prepared from bovine corpora luteal (CL) obtained from the slaughterhouse. The parent structure of the analog was a dominant feature in determining the affinity for the respective PG binding site. Luteolysis was determined in cattle following intramuscular injection of various doses of prostaglandin once between days 6 and 14 after estrus and measuring CL regression by ovarian palpation per rectum, interval between injection and return to estrus and duration of the subsequent estrous cycle. A dose which was luteolytic was established for each of eight PGF-type compounds, and a dose which was not luteolytic was also established. There appeared to be limited association between the relative affinity for the PGF2alpha specific site in vitro and the estimated luteolytic dose range of these PGF analogs when tested in cattle. Differences in in vivo luteolytic potency for the compounds tested could not be explained by differences in binding affinity. Differences in metabolism and absorption may also be important in the determination of in vivo potency.
To determine the incidence of and risk factors in cerebrovascular disease in Manitoba, all 1367 new cases in defined areas (population, 660 391) in an 18-month period were studied. Pertinent data were collected from hospital records, death certificates and autopsy reports. The annual incidence of cerebrovascular disease in these areas was 138/100 000 and the incidence was generally higher in men than in women. The incidence of cerebral infarction (INF) and that of hemorrhage (HGE) were similar in men and women less than 50 years old; thereafter the incidence of INF increased faster with age than did that of HGE, the disparity being greater in men than in women, whereas the incidence of HGE increased at similar rates in the two sexes. The incidence of INF was significantly greater in men than in women in urban areas, and in men it was greater in urban than in rural areas. Elevated concentrations of serum lipids and smoking are implicated as risk factors in INF, and hypertension as a risk factor in HGE.
The synthesis of dl-4,5,6-trinor-3,7-inter-m-phenylene-3-oxaprostaglandins of the E1 and F1alpha series from 6-endo-(1-heptenyl)-bicyclo[3:1:0]hexan-3-one (III), is described. Preliminary biological screening data for gerbil colon smooth muscle stimulation, rat blood pressure and substrate specificity toward 15-hydroxyprostaglandin dehydrogenase is presented. Platelet function studies, both in vitro and in vivo of dl-4,5,6-trinor-3,7-inter-m-phenylene-3-oxa-PGE1, methyl ester (VIII) are presented.
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This report describes the 20-year blood pressure behaviour of 3869 selected young North American males.Initial mean systolic and diastolic pressures were higher than those recorded five years later; after that pressures increased progressively. The effect of initial selection was evident for the first 10 years of exposure.A significant relationship was demonstrated between all initial systolic and diastolic levels and the 20-year blood pressure behaviour. Systolic pressure was not affected by age until age 50 and diastolic until age 45. After that a significant relationship was demonstrated.In 20 years multiple readings >/= 140 and/or >/= 90 mm. Hg were recorded in 26% of the population. Increases in pressure usually extended over many years. Commonly they were labile, fluctuating above and below 140/90 mm. Hg. In a small, clearly defined group, accelerated increases reached high levels in three to 10 years.
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