Receptor-binding and down-regulatory properties of 22000-Mr human growth hormone and its natural 20000-Mr variant on IM-9 human lymphocytes.

Our earlier binding studies of the 22000- and 20000-Mr variants of human growth hormone (somatotropin) to pregnant-rabbit liver and mammary receptors [Closset, Smal, Gomez & Hennen (1983) Biochem. J. 214, 885-892] suggested that the 20000-Mr variant was a lower-affinity analogue of the 22000-Mr molecule. Since the receptor population in these tissues is not fully characterized, we have now investigated the binding of both variants to the well-characterized and highly specific human-growth-hormone receptor of the human lymphocyte IM-9 cell line. The maximum bindability of radioiodinated 22000- and 22000-Mr to IM-9 cells was 60 and 45% respectively. Both hormone variants have essentially the same binding characteristics: slow association (equilibrium reached in 8-10h at 30 degrees C), poor reversibility ('tight binding'), linear Scatchard plot, same specificity as shown by lack of competition by bovine, porcine or equine growth hormones or human growth hormone-(32-46)-(missing in the 20000-Mr variant),-(1-134)- and -(141-191)-peptides. Both unlabelled hormones inhibit binding of both tracers completely, with the 20000-Mr variant being only half as potent as the 22000-Mr one. The apparent affinity is 2.8 X 10(9)M-1 for the 22000-Mr variant and 1.6 X 10(9)M-1 for the 20000-Mr variant. This decreased affinity of the 20000-Mr variant appears to be due to a lower association rate constant. Concentrations (5 ng/ml) of the two variants that occupy about 15% of the total sites induce a marked down-regulation of the receptors after 18h incubation, but the 20000-Mr variant (50% decrease) has a smaller effect than the 22000-Mr variant (75% decrease). Thus the only consequence of the residues-32-46 deletion in the 20000-Mr variant is a lower association rate and affinity for the IM-9 lymphocyte human-growth-hormone receptor. The close binding characteristics of the two forms suggest that the known differences in their insulin-like effects cannot be explained by differences in the nature of their interaction with the human-growth-hormone receptor.     

Prevalence,control and awareness of high blood pressure among Canadian adults. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To estimate the prevalence and distribution of elevated blood pressure (BP) among Canadian adults and to determine the level of control, treatment, awareness and prevalence of other risk factors among adults with high BP. DESIGN: Population-based cross-sectional surveys. SETTING: Nine Canadian provinces, from 1986 to 1990. PARTICIPANTS: A probability sample of 26,293 men and women aged 18 to 74 years was selected from the health insurance registers in each province. For 20,582 subjects, BP was measured at least twice. Nurses administered a standard questionnaire and recorded two BP measurements using a standardized technique. Two further BP readings, anthropometric measurements and a blood specimen for lipid analysis were obtained from those subjects who attended a clinic. OUTCOME MEASURES: Mean values of systolic and diastolic BP, prevalence of elevated BP using different criteria, and prevalence of smoking, elevated blood cholesterol, body mass index, physical activity and presence of diabetes by high BP status are reported. MAIN RESULTS: Sixteen percent of men and 13% of women had diastolic BP of 90 mm Hg or greater or were on treatment (or both). About 26% of these subjects were unaware of their hypertension, 42% were being treated and their condition controlled, 16% were treated and not controlled, and 16% were neither treated nor controlled. Use of non-pharmacologic treatment of high BP with or without medication was low (22%). Hypertensive subjects showed a higher prevalence of elevated total cholesterol, high body mass index, diabetes and sedentary lifestyle than normotensive subjects. Most people with elevated BP were in the 90 to 95 mm Hg range for diastolic pressure and 140 to 160 mm Hg range for systolic pressure. Prevalence of high isolated systolic BP sharply increased in men (40%) and women (49%) 65 to 74 years old. CONCLUSIONS: The relatively low level of control of elevated BP calls for population and individual strategies, stressing a non-pharmacologic approach and addressing isolated systolic hypertension in the elderly.     

The differential effects of the carcinogen dimethylnitrosamine on isocitrate and 6-phosphogluconate metabolism in single intact cells

A microspectrofluorimetric study is made of the influence of dimethylnitrosamine on NADP reduction, following sequential microinjections into the same L cell, of two substrates: (1) isocitrate, with activity of isocitrate dehydrogenase both in the extramitochondrial and intramitochondrial compartments, (2) 6-phosphogluconate, with activity of the dehydrogenase in the extramitochondrial compartment. In control L cells a two-step reduction of NAD(P) is obtained followed by relatively slow reoxidation. In the minutes which follow addition of carcinogen, e.g., dimethylnitrosamine, to the cell medium the isocitrate and 6-phosphogluconate-induced transient NADP reoxidation is decreased in magnitude compared to control, while the rate constant of NADPH reoxidation is considerably accelerated, possibly due to requirements at the level of the microsomal metabolizing system. Observations within the first hour of carcinogen addition suggest an interesting system for evaluating the immediate actions of carcinogens at extranuclear sites: i.e., a comparative study of NADP reduction-reoxidation rate constants via injection of substrates for extra- vs. intramitochondrial pathways.     

Effect of retinoic acid on the aggregation of erythrocytes and leukocytes in the blood

Human and animal blood smear staining with PAPh has revealed mononuclear leukocyte-erythrocyte aggregates. Administration of retinoic acid increased concentration and dimensions of these aggregates and was followed by preferential accumulation of PAPh-negative osmotically unstable erythrocytes. Similar changes were detected in the blood samples of women engaged in the production of retinoic acid. Aggregate concentration showed positive correlation with erythrocyte sedimentation rate and no correlation with prothrombin time.     

Fowler central slip tenotomy for old mallet deformity

Fowler's central slip tenotomy for old mallet deformity is a well-known, but apparently seldom used procedure. Although the vast majority of patients with mallet finger can be successfully treated by well-known conservative techniques, occasional patients, such as the 11 reported here, will have enough difficulty with a chronic mallet finger to warrant rebalancing of the extensor apparatus by means of central slip tenotomy.