Intracranial dural arteriovenous fistulas with retrograde cortical venous drainage: assessment with cerebral blood volume by dynamic susceptibility contrast magnetic resonance imaging.

BACKGROUND AND PURPOSE: Retrograde cortical venous drainage (RCVD) is the most major risk factor for aggressive behavior of intracranial dural arteriovenous fistulas (DAVF). The purpose of this study was to assess the efficacy of relative cerebral blood volume (rCBV) map for RCVD in patients with DAVF. METHODS: Ten patients with angiographically proven DAVF with RCVD, 2 reference patients with DAVF without RCVD, and 10 control subjects underwent examinations with dynamic susceptibility contrast (DSC)-MR imaging. Four patients with DAVF with unilateral RCVD were evaluated, before and after treatment. The calculation of mean rCBV ratio was performed on a hemispheric basis. The mean rCBV ratio was defined as the value on one side (higher value side) divided by that on the other side (lower value side). RESULTS: In all patients with DAVF with RCVD, the rCBV map showed an increase in rCBV of the angiographically proved affected hemisphere. In 2 reference patients with DAVF without RCVD and all control subjects, the rCBV map showed no increase of rCBV. The mean rCBV ratio in patients with DAVF with RCVD was significantly higher than that of control subjects (P = .0002). Treatment response for RCVD was indicated by a decrease of CBV on the rCBV map and by a decrease of 22% in the mean rCBV ratio. CONCLUSIONS: Increased rCBV by DSC-MR correlated with RCVD in patients with DVAF. The assessment with rCBV for RCVD may be more quantitative than that with angiogram.

Intestinal knockout of Nedd4 enhances growth of Apcmin tumors.

Nedd4 (Nedd4-1) is an E3 ubiquitin ligase that belongs to the HECT family and comprises a C2-WW(n)-HECT domain architecture. Although it has been reported to regulate growth factor receptors and cellular signaling, its role in cancer development has been controversial, with some studies proposing that it promotes cancer while others suggest it inhibits tumor growth. Here, we tested the effect of Nedd4 on intestinal tumor formation and growth using Nedd4-knockout mice (Nedd4 floxed (fl) mice crossed to villin-Cre mice). Although we find that knockout of Nedd4 on its own does not cause tumor growth, its knockout in the context of Apc+/min-derived colorectal tumors leads to augmentation of tumor growth, suggesting that Nedd4 normally suppresses intestinal WNT signaling and growth of colonic tumors. WNT signaling microarray, immunoblotting and immunohistochemistry analyses of tumors derived from the Villin-Cre;Nedd4fl/fl;Apc+/min colons demonstrated elevated expression of the WNT upstream effectors LEF1 (full length) and YY1 in these tumors relative to control (Apc+/min alone) tumors. Together, these results suggest that Nedd4 suppresses colonic WNT signaling and tumor growth, at least in part, by suppressing the transcription factors LEF1 and YY1.

Cell-cell adhesion-mediated tyrosine phosphorylation of nectin-2delta, an immunoglobulin-like cell adhesion molecule at adherens junctions.

We have recently found a novel functional unit of cell-cell adhesion at cadherin-based adherens junctions, consisting of at least nectin, an immunoglobulin-like cell adhesion molecule, and afadin, an actin filament-binding protein which connects nectin to the actin cytoskeleton. Among the members of the nectin family, we have found here that nectin-2delta is tyrosine-phosphorylated in response to cell-cell adhesion. Expression of E-cadherin induced tyrosine phosphorylation of nectin-2delta, while disruption of cell-cell adhesion by an anti-E-cadherin antibody reduced the tyrosine phosphorylation of nectin-2delta. An inhibitor specific for Src family kinase or expression of Csk reduced tyrosine phosphorylation of nectin-2delta. In addition, Src kinase tyrosine phosphorylates the recombinant cytoplasmic region of nectin-2delta in vitro. The major tyrosine phosphorylation site of nectin-2delta was Tyr505 in the cytoplasmic region, because the mutant nectin-2delta, of which Tyr505 was replaced by Phe, showed a loss of tyrosine phosphorylation in vivo and in vitro. These results, together with our recent observations, indicate that the cadherin-catenin system and the nectin-afadin system are closely connected to each other. The cadherin-mediated cell-cell adhesion system may link to the activation of a Src family kinase, that is, at least in part, responsible for the tyrosine phosphorylation of the cytoplasmic region of nectin-2delta. Oncogene (2000) 19, 4022 - 4028.

Mn(III)-containing acid phosphatase. Properties of Fe(III)-substituted enzyme and function of Mn(III) and Fe(III) in plant and mammalian acid phosphatases.

The function of Mn(III) in plant acid phosphatase has been investigated by a metal-substitution study, and some properties of the Fe(III)-substituted enzyme were compared with those of the native Mn(III) enzyme and mammalian Fe(III)-containing acid phosphatases. 19F nuclear magnetic resonance (NMR) and proton relaxation rate measurements showed that inhibitors such as F- and nitrilotriacetic acid interact with paramagnetic Mn(III) active site. The 31P-NMR signal of the enzyme-phosphate complex was also broadened by the paramagnetic effect of Mn(III). In the metal-substitution experiments of the Mn(III)-acid phosphatase with Fe(III), Zn(II) and Cu(II), only the iron gave satisfactory substitution. The Fe(III)-substituted plant acid phosphatase exhibited an absorption maximum at 525 nm (epsilon = 3000), typical high-spin ferric ESR signal at g = 4.39, and lower pH optimum (pH 4.8) than the native Mn(III)-enzyme (pH 5.8). The phosphatase activity of the Fe(III)-substituted enzyme was reduced to about 53% of that of the native enzyme. The substrate specificities of both metallophosphatases were remarkably similar, but different from that of the Fe(III)-containing uteroferrin. The present results indicate that Mn(III) and Fe(III) in the acid phosphatase play an important role on effective binding of phosphate and acceleration of hydrolysis of phosphomonoesters at pH 4-6.

Spectroscopic studies on bleomycin-iron complexes with carbon monoxide, nitric oxide, isocyanide, azide, and cyanide and comparison with iron-porphyrin complexes.

The bleomycin-iron complexes with CO, NO, C2H5NC, OH-, N-3, CN-, and CH3NH2 were characterized by electronic, ESR, 1H-NMR, and Mössbauer spectroscopies and the findings were compared with the corresponding hemoprotein complexes. The 1H-NMR and Mössbauer features for the CO and C2H5NC adducts of the bleomycin-Fe(II) complex are consistent with an S = 0 ferrous assignment. The OH-, CH3NH2, and N-3 adducts of the bleomycin-Fe(III) complex show the ESR, 1H-NMR, and Mössbauer spectra typical of a low-spin Fe(III). The unique Mössbauer parameters of the bleomycin-Fe(II)-NO complex demonstrate mixing between the NO pi- and the Fe 3d-orbitals. The magnitude of the proton chemical shifts over +/- 50 ppm indicates a high-spin ferric type for the bleomycin-Fe(III)-CN complex. The Mössbauer parameters (delta EQ = 0.89 and delta = 0.48 mm/s) of the CN- adduct differ substantially from those of typical low-spin hemoprotein-cyanide complexes. Except for the CN- adduct, the Mössbauer and crystal field parameters of these bleomycin-iron complexes are similar to those of the corresponding hemoprotein complexes.

Elucidation of the thermal stability of the neutral proteinase II from Aspergillus oryzae.

The neutral proteinase II from Aspergillus oryzae (NpII) is a zinc proteinase with three intramolecular disulfide bonds. NpII is most unstable after 10 min at about 75 degrees C, but regains stability beyond this temperature and is relatively stable at 100 degrees C. We analyzed the thermal stability of wild-type NpII and apo NpII. The results suggested that NpII unfolds reversibly upon incubation up to 100 degrees C, and that the irreversible inactivation observed is mainly due to autoproteolysis. To further understand the stability, a mutant NpII (Cys78-->Ala) lacking one of the disulfide bonds, was produced in a heterologous yeast expression system. The mutant NpII showed a similar stability profile, but the most unstable temperature and the most catalytically active temperature decreased to the same extent (around 10 degrees C), confirming that autoproteolysis is the main cause of the irreversible inactivation. Several lines of evidence presented in this study demonstrated that the thermal stability of o++NpII is attributed to reversible thermal unfolding and autoproteolysis.

The obese gene product, leptin: possible role in obesity-related hypertension in adolescents.

OBJECTIVE: The mechanism of the association between obesity and hypertension is not clear. The recently discovered obese gene product, leptin, the levels of which increase in obese subjects, has been shown to reduce food intake and increase sympathetic nervous system activity in animal studies. The present study was undertaken to elucidate the relationship between blood pressure and factors related to obesity, including leptin, in different age groups. METHODS: The subjects were 348 Japanese male adolescents (15-17 years old) and 165 men (40-59 years old) not taking medication for hypertension, diabetes mellitus or hyperlipidaemia. Height, weight, blood pressure, heart rate, plasma glucose, lipid profiles, serum insulin and leptin levels were measured in the morning after an overnight fast RESULTS: Body mass index (BMI), serum leptin level and the homeostasis model insulin resistance index increased in the order of blood-pressure category (i.e. normotensive < high normal < hypertensive) in both the male adolescents and the middle-aged men. In addition, simple linear regressions revealed that both systolic and diastolic blood pressure correlated significantly with serum leptin and the insulin resistance index in both groups. Even after adjustment for age and BMI, the correlation of mean blood pressure with leptin remained in the obese adolescents (r2 = 0.390, P = 0.02). The heart rate also correlated with leptin in the adolescents (r = 0.18, P< 0.001), but not in the middle-aged subjects (r = 0.04). Even after adjustment for age and BMI in adolescents, serum leptin correlated significantly with heart rate. CONCLUSION: These results suggest a role for leptin in obesity-related hypertension, especially in adolescents.

Determinants for the development of hypertension in adolescents. A 6-year follow-up.

OBJECTIVE: This study was aimed to evaluate the determinants of elevated blood pressure (BP) in adolescents. DESIGN AND METHODS: We retrospectively evaluated the BP and anthropometric data in 419 Japanese students (268 males and 151 females) during high school and university. Their annual health records were analysed for BP, heart rate, height and body weight between the ages of 15 and 21 years. RESULTS: The number of hypertensive students did not vary significantly during the 6 years. Concerning changes in BP categories according to the modified JNCVI classification between the ages of 15 to 21 years, 150 males kept a normal BP (keeping normal BP group); 39 males developed high BP (developing high BP group); 37 males kept high BP (keeping high BP group); and 42 males became normal BP (becoming normal BP group). The majority of females (n = 144, 95.4%) were included in the keeping normal BP group. In male students, both the keeping and becoming normal BP groups, especially the latter, showed a significant decrease in heart rate over the 6 years, while the other two groups showed no change. The height and body weight of each of the four groups showed a significant increase, but the body mass index (BMI) of the males in the becoming normal BP group did not increase over the 6 years. Body weight and BMI at the age of 15 years in the male keeping normal BP group were significantly below that of the other three groups; this difference persisted at the age of 21 years. Furthermore, male university students who showed a BP above 'high-normal' at the age of 21 years exhibited a significantly higher BP, heart rate, body weight and BMI than did the normotensives, when they were high school students. Stepwise regression analysis of the data showed that the best predictors of BP at the age of 21 years were the initial high school BP and BMI levels and changes in BMI and heart rate during the 6-year period for male students. CONCLUSION: Results indicate that the BP and BMI during high school and the changes in BMI and heart rate from high school to university influenced the BP at the age of 21 years in male students. Data indicate that information on the prevention and management of hypertension including weight control should begin early, especially in male adolescents.

Relation of home blood pressure to body weight in young normotensive men with or without family history of hypertension.

We investigated the relation between home blood pressure (BP) and body weight in 38 young normotensive men (mean age, 16 years) whose parents were normotensive (PNT group) and 34 age- and sex-matched normotensive men, one or both of whose parents were hypertensive (PHT group). Although causal BP measurements were similar in both groups, home systolic BP was significantly higher in the PHT group (123 +/- 1 mm Hg) than in the PNT group (116 +/- 1 mm Hg). Body weight was significantly greater in the PHT group (66.0 +/- 1.4 v 61.8 +/- 1.3 kg, P < .05) and body mass index (BMI) was not significantly higher in the PHT group (22.4 +/- 0.5 v 21.3 +/- 0.5 kg/m2, P = .09). Body weight (r = 0.38) and BMI (r = 0.42) were significantly correlated with home systolic BP in the PHT group. There were no differences in serum lipid or uric acid concentrations between the two groups. Our results showed that young normotensive subjects with a genetic predisposition to hypertension weighed more and had higher home systolic BPs compared with subjects without a family history of hypertension. Our observations further indicated a close relationship between a family history of hypertension and increased body weight, even in young normotensive men.

Importance of the renin-angiotensin system in sodium regulation in essential hypertension.

To elucidate the effect of natriuretic and antinatriuretic factors on the excretion of an intravenous sodium load, we observed the natriuretic responses of 12 patients with essential hypertension (EHT) and 7 age- and sex-matched normotensive (NT) subjects following the intravenous administration of 1500 mL of normal saline over a 3 h period. After saline infusion, both groups showed increases in urinary sodium excretion (UNaV). The increases in glomerular filtration rate (GFR), atrial natriuretic peptide (ANP) and urinary dopamine excretion (UDAV) and the suppression of plasma renin activity (PRA) were similar in both groups. However, no significant change in blood pressure (BP) was seen in either group. Since significant negative linear correlations between the basal level of PRA and percent change in UNaV or GFR were seen only in EHT, we observed the influence of suppressing the renin-angiotensin system with a converting enzyme inhibitor. After a 7 day treatment with enalapril, GFR and UNaV in EHT after saline infusion were comparable to data obtained in the absence of enalapril, despite a reduction in preexpansion BP. Furthermore, a significant positive correlation between the basal BP and the percent increase in UNaV was seen among EHT after enalapril treatment. These results suggest that the state of the renin-angiotensin system is important in renal sodium excretion in EHT.

Leisure time physical activity and insulin resistance in young obese students with hypertension.

To investigate the hypothesis that insulin resistance plays a role in the etiology of hypertension and hyperlipidemia, we measured serum lipid levels, the fasting glucose/insulin ratio, and the insulin response to oral glucose (GTT) in a group of young obese subjects (n = 21) with hypertension and normal glucose tolerance and in normotensive subjects (n = 36) with normal glucose tolerance, matched for age and body mass index. Leisure time physical activity was evaluated by a questionnaire outlining three levels of physical activities during leisure time. Subjects with hypertension had higher fasting serum insulin (19 +/- 2 v 13 +/- 1 microU/mL, P < .01) and lower fasting glucose/insulin ratio (5.3 +/- 0.2 v 7.1 +/- 0.5 mg/dL/microU/mL, P < .01) than normotensive subjects. Subjects with hypertension had higher peak serum insulin and lower plasma glucose area/insulin area ratio in response to glucose (1.8 +/- 0.2 v 2.4 +/- 0.2 mg/dL/microU/mL, P < .05) than normotensive subjects. Serum total cholesterol, low-density cholesterol, and triglycerides were higher in the obese hypertensive subjects than in obese normotensive ones. Blood pressure correlated with either fasting serum insulin, fasting glucose/insulin ratio, or glucose area/insulin area ratio during GTT. The level of leisure time physical activities was lower in obese hypertensive subjects than in obese normotensive ones. There were significant correlations between the levels of physical activity and the fasting plasma glucose/insulin ratio (r = 0.371, P < .01) or the fasting serum insulin concentration (r = -0.282, P < .05). The study provided evidence that a low level of leisure time physical activity is associated with insulin resistance and resultant hyperinsulinemia, which are the key metabolic abnormalities that link hypertension, obesity, and hyperlipidemia in young subjects.

Effects of body weight control on changes in blood pressure: three-year follow-up study in young Japanese individuals.

Numerous epidemiological studies have shown a close relationship between obesity and hypertension. However, there have been few reports on the relationship between changes in the body weight and blood pressure of lean to normal-weight young subjects. The purpose of this study was to investigate the effects of body weight control on blood pressure in lean to obese young Japanese individuals in a 3-year follow-up study. University students (3,558 males and 1,418 females, aged 18.6+/-0.8 in 1994) were classified into 4 groups according to the baseline body mass index (BMI), and were followed up for 3 years. Among male students, changes in body weight were significantly correlated with changes in blood pressure during the 3 years in all 4 BMI groups, and the correlation coefficient was larger in the group with higher baseline BMI. Positive correlations between changes in body weight and changes in heart rate were noted only in the obese and mildly-obese groups. Also in female students, positive correlations were observed between changes in body weight and changes in blood pressure in lean to obese groups. However, no correlations between changes in body weight and changes in heart rate were noted in any of the female groups. To summarize, close correlations were observed between changes in body weight and those in blood pressure during the 3 years in both male and female university students. These findings suggest the importance of body weight control not only in obese but also in normal to mildly-obese young subjects in reducing or preventing an increase in blood pressure. There could be, however, a gender difference in the effects of body weight change on heart rate.

Participation in school sports clubs and related effects on cardiovascular risk factors in young males.

The effects of belonging to sports clubs on male high school students was evaluated. The relationships between the type and extent of school-based exercise were examined in conjunction with percent body fat, blood pressure (BP), and other key metabolic parameters. A total of 264 male Japanese high school students (age range: 17-18 years old) were studied. Percent body fat was measured and blood was collected in the fasting state during a routine health check. Subjects were divided into two groups. The exercise (E) group (n=150) included students who had belonged to a sports club during the past 2 years. The non-exercise (NE) group (n=114) included students who did not belong to a sports club during the past 2 years. The body mass index was significantly greater in group E (21.7 +/- 2.3 (SD) kg/m2) than in group NE (20.7 +/- 2.6 kg/m2, p < 0.01). However, the percent body fat in group E (13.6 +/- 3.4%) was significantly lower than that in group NE (14.9 +/- 3.8%, p < 0.01). The diastolic BP and heart rate in group E (64 +/- 7 mmHg, 70 +/- 11/min) were significantly lower in group E than in group NE (66 +/- 8 mmHg, p < 0.05; 76 +/- 14/min, p < 0.01). The serum triglyceride level was significantly lower, and the HDL cholesterol level was higher in group E than in group NE. The homeostasis model assessment (HOMA) index, used as an index of insulin resistance, was similar in the two groups. However, the level of the HOMA index was significantly lower among the 62 subjects in group E who preferred highly dynamic exercise (1.50 +/- 0.46) than it was among those in group NE (1.66 +/- 0.49, p < 0.05). Results indicate that belonging to sports clubs influences the BP and lipid profiles of adolescent males, as well as their percent body fat. In view of the reduction of cardiovascular risk factors, it is recommended that even young males practice regular exercise, especially aerobic exercise.

Sexual differences in relationships between birth weight or current body weight and blood pressure or cholesterol in young Japanese students.

This study was designed to examine the relationships between birth weight or current body weight and blood pressure (BP) or cholesterol in 178 Japanese high school students (98 male, 80 female, age 15-16 yr). All subjects were born after a full-term pregnancy (gestational age > or = 38 wk) with a birth weight > or = 2,500 g; these data were obtained from routine obstetrical records. At a health check-up, nurses used an automatic device to perform two consecutive BP measurements with each subject in a sitting position after resting for at least 5 min. Serum total and high-density lipoprotein (HDL) cholesterol levels were measured. Birth weight was not related to BP, but was inversely related to serum total cholesterol in both males (r= -0.241, p < 0.05) and females (r= -0.351, p < 0.01). Current body weight was significantly related to systolic BP (r=0.369, p<0.01), diastolic BP (r=0.216, p<0.05), and HDL cholesterol level (r= -0.224, p < 0.05) in males, but not in females. Although no relationship was demonstrated between birth weight and BP level in young Japanese students without intrauterine growth retardation, an inverse relationship between birth weight and serum total cholesterol level was found. There was a gender difference in the relationship between current body weight and either BP or HDL cholesterol in these subjects.

Insulin resistance syndrome in adolescents and adults.

This study was designed to investigate the possibility of sex and age differences in the insulin-blood pressure relationship in a general Japanese population with a wide age range. Fasting serum insulin, lipids, plasma glucose, blood pressure and anthropometric measurements were made on 1,537 men and 843 women aged 16 to 65 years. Of the 2,380 subjects in the present analysis, 290 (184 men, 106 women) were hypertensive. When divided into four age groups (16 to 17, 21 to 22, 30 to 49 and 50 to 65 years), the male hypertensive subjects were found to have significantly higher fasting insulin levels, triglycerides levels and body mass index and lower glucose/insulin ratios than normotensive male subjects in all age groups. In the women, there was no significant difference in serum insulin levels or glucose insulin ratios between the hypertensive and normotensive groups in any age group. Simple correlation analysis showed that blood pressure was statistically significantly correlated with serum insulin levels and body mass index in the men in all age groups. In women, the correlation between blood pressure and serum insulin was insignificant in the 21- to 22-year-old age group. In men but not women, multivariate analysis showed that blood pressure was significantly and independently correlated with fasting serum insulin levels. The results of this study suggests the existence of sex and age differences in the insulin-blood pressure relationship in a Japanese population.

Detecting meningeal carcinomatosis from breast cancer with thallium-201 SPECT.

Thallium-201 (201Tl) scintigraphy is one of the imaging methods used in the detection of various tumors including brain metastasis. We evaluated a patient with meningeal carcinomatosis from breast cancer by using 201Tl single-photon emission computed tomography (SPECT). Meningeal spread of a tumor was noted on enhanced CT. SPECT revealed tumor localization in meningeal carcinomatosis. These results suggest that SPECT with 201Tl may be useful in detecting meningeal carcinomatosis from breast cancer.

Circulatory and plasma catecholamine responses to mental stress in young subjects with two different types of hypertension.

To determine whether any differences exist between young male subjects with elevated diastolic and systolic blood pressure (BP) and those with only an elevated systolic BP, the responses of BP and plasma catecholamines to a mental arithmetic test were studied in 11 young men (mean age of nineteen years) with BP of > or = 140/90 mm Hg at a routine health check-up (group I-hypertension [HT]), 26 age-matched men with only elevated systolic BP (> or = 140 mm Hg) (group II-HT), and 12 age-matched normotensive (NT) men (< 140/90 mm Hg). During an arithmetic test, group I-HT showed a significantly higher increment of systolic BP (+14.5-18.0%) than group II-HT (+9.3-10.2%) and NT controls (+6.4-8.2%). However, no significant difference in BP response was seen between group II-HT and NT controls. Plasma norepinephrine in group I-HT showed a significant increase after the test, (171 +/- 23-->202 +/- 27 pg/mL), whereas group II-HT and NT controls showed no change. No significant difference occurred in epinephrine response among the three groups. These results suggest that the young male subjects with screening BP above 140/90 mm Hg are hyperreactive to a mental stress as compared with subjects with only elevated systolic BP or NT controls.

Angiotensin II pressor activity depends on medial and lateral anterior hypothalamic pathways.

The preoptic region of hypothalamus was disconnected from caudal structures with two different-size knife cuts in rats to investigate the pathway responsible for the effects of intracerebroventricular (ICV) and intravenous (IV) angiotensin II (ang II) on blood pressure and arginine vasopressin (AVP) release. Seven days after surgery ICV ang II (125 ng) in sham-operated (sham) rats increased mean arterial pressure (MAP) (+23 +/- 3 mmHg) and decreased heart rate (HR) (-58 +/- 5 beats/minute). However, ICV ang II had no effect on MAP or HR of rats with a large (preoptic-hypothalamic disconnection) cut. Both the pressor response (+12 +/- 2 mmHg) and the bradycardia (-39 +/- 6 beats/minute) were significantly reduced by a small (medial preoptic-hypothalamic disconnection) cut. The increased plasma AVP to ICV ang II in sham rats (9.8 +/- 3.6 pg/mL) was abolished in large-cut rats and attenuated in small-cut rats (3.2 +/- 0.7 pg/mL). IV bolus injection of ang II (125 ng) in sham rats increased MAP by 43 mmHg, whereas large-cut rats showed a blunted (25%) pressor response. The pressor response to IV infusion of ang II (8 ng/20 microL/minute for 15 minutes) was diminished in large-cut rats (+4 +/- 1 mmHg) as compared with that in sham rats (+19 +/- 2 mmHg). Both cuts transected the projection between the periventricular tissue surrounding the anteroventral third ventricle and supraoptic nucleus, but the supraoptic-neurohypophyseal pathway was severed only by the large cut.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of L-dopa in young patients with hypertension.

The effects of L-dopa on blood pressure, heart rate, plasma renin activity, norepinephrine, epinephrine and prolactin were studied in a randomized single-blind trial in 36 patients with essential hypertension. In response to L-dopa, 250 mg administered orally, the blood pressure decreased significantly as compared with the results of placebo treatment. The heart rate and plasma norepinephrine and epinephrine were unchanged. The plasma renin activity and prolactin decreased as a result of L-dopa administration. The administration of a peripheral DA2 dopamine receptor blocker, domperidone (20 mg, orally) prevented the L-dopa-induced reduction in plasma prolactin but failed to block the fall in blood pressure and plasma renin activity. These results suggest that the blood pressure-lowering effect of L-dopa may be mediated through multiple sites involving D1 dopamine receptors, the central nervous system, and the renin-angiotensin system.

Effects of contact lens wear on mitosis of corneal epithelium and lactate content in aqueous humor of rabbit.

Various types of contact lenses, i.e., poly-methyl-methacrylate hard lenses, poly-2-hydroxyethyl-methacrylate soft lenses and two kinds of gas-permeable hard lenses with different permeabilities to oxygen, were placed on one eye of the albino rabbit for varying lengths of time. Using the fellow eye as the control, studies were carried out of the effects of the lens wear on the mitosis in the corneal epithelium and the lactate concentration in the aqueous humor. The contact lens wear suppressed the mitosis and increased the concentration of aqueous lactate, the degree of changes being greater as the permeability of the lens to oxygen decreased and the period of wear became longer.