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Biomedical subjects

Y Imai

Publications and source records attributed to Y Imai.

At least 415 records · Page 23Linked to original sources

Prediction of mortality by ambulatory blood pressure monitoring versus screening blood pressure measurements: a pilot study in Ohasama.

OBJECTIVE: To compare the prediction of mortality by ambulatory blood pressure monitoring and screening blood pressure measurements in a general population. DESIGN: A prospective cohort study. PATIENTS AND METHODS: We obtained blood pressure data for 1542 subjects (565 men and 977 women) aged > or = 40 years who were followed up for up to 8.1 years (mean 5.1 years). Subjects were subdivided into five groups according to their ambulatory and screening blood pressure levels. The prognostic significance of blood pressure for mortality was examined by the Cox proportional hazards regression model. RESULTS: The association between blood pressure level and mortality was more distinctive for the ambulatory blood pressure than it was for the screening blood pressure. The risk of cardiovascular mortality increased significantly for the highest quintiles of 24 h ambulatory blood pressure, whereas there was no significant association between the screening blood pressure and the cardiovascular mortality. When both 24 h and screening blood pressure values were included in the Cox model, only the systolic ambulatory blood pressure was related significantly to the increased risk of cardiovascular mortality. CONCLUSIONS: The ambulatory blood pressure had a stronger predictive power for mortality than did the screening blood pressure. This appears to have been the first study of the prognostic significance of ambulatory blood pressure monitoring versus screening blood pressure measurements in a general population.

Adult↗

Factors affecting the nocturnal decrease in blood pressure: a community-based study in Ohasama.

OBJECTIVE: To investigate factors affecting the nocturnal decrease in blood pressure. DESIGN: A cross-sectional study of 823 community-based untreated subjects aged > 20 years. Screening and ambulatory blood pressures were measured and the effects of age and the ambulatory blood pressure on the nocturnal decrease were examined. RESULTS: The magnitude of the decrease and the percentage decrease in the nocturnal blood pressure increased with increasing daytime ambulatory blood pressure and decreased with increasing night-time ambulatory blood pressure. Although the magnitude of the nocturnal decrease in blood pressure increased with increasing daytime blood pressure, the nocturnal blood pressure levels in hypertensives were still higher than those in normotensive subjects. The magnitude decreased with increasing age for men but not for women, whereas the percentage decrease decreased with increasing age both for men and for women. The SD of the 24 h blood pressure correlated strongly to the magnitude of the nocturnal decrease (systolic blood pressure r = 0.62, P < 0.0001; diastolic blood pressure r = 0.52, P < 0.0001), suggesting that the SD of the 24 h blood pressure is representative of the nocturnal decrease. A minimal nocturnal decrease was observed frequently in elderly normotensive men but infrequently in hypertensive individuals from the general population. A marked nocturnal decrease was observed frequently in hypertensive women aged > 70 years. CONCLUSION: Although the magnitude of the nocturnal decrease in blood pressure increased with increasing daytime blood pressure, the nocturnal blood pressure levels increased with increasing daytime ambulatory blood pressure. Therefore, the blood pressure in hypertensive subjects should essentially be lowered throughout the 24 h period. A marked nocturnal decrease in blood pressure in some elderly hypertensive women was observed without treatment. The nocturnal blood pressure levels of such subjects should be considered during treatment.

Adult↗

Intrasellar pituitary gangliocyto-adenoma presenting with acromegaly: case report.

OBJECTIVE AND IMPORTANCE: A gangliocytoma in the sellar region is extremely rare. We describe a rare case of intraseller gangliocytoma coexisting with a growth hormone-producing pituitary adenoma, which presented with acromegaly. CLINICAL PRESENTATION AND INTERVENTION: A 64-year-old woman was admitted to our hospital with headache and acromegaly. Endocrinological studies revealed an elevated serum level of growth hormone (GH). Magnetic resonance imaging showed a tumor at the intrasellar and suprasellar regions. The tumor was totally removed via a transsphenoidal approach. RESULTS: A histological examination of the resected specimen showed areas of ganglionic cells and adenomatous cells. Immunohistochemical examination demonstrated GH-releasing hormone-positive ganglionic cells and GH-positive pituitary adenoma. CONCLUSION: Based on these immunohistochemical findings, we hypothesized that the intrasellar gangliocytoma promoted the growth of the pituitary adenoma, which had been transformed from a region of pituitary hyperplasia by chronic overstimulation from excess GH-releasing hormone produced by the intrasellar gangliocytoma.

Acromegaly↗

p16INK4 gene mutations are relatively frequent in ampullary carcinomas.

A high incidence of gene mutations or deletions of p16INK4, a cell cycle regulator which inhibits the activity of cyclin-dependent kinase 4/cyclin D complex and blocks the G1-to-S transition, has been reported in pancreato-biliary tract cancers. In order to investigate p16INK4 gene alterations in sporadic ampullary carcinomas, 17 sporadic ampullary carcinomas were examined. After histological diagnosis, DNA samples extracted separately from both cancerous and normal paraffin-embedded tissues were investigated. Loss of heterozygosity (LOH) was investigated utilizing 3 microsatellite markers on 9p21-22, and a mutational analysis was performed by cloning and sequencing. LOH was observed in 3 cases (17.6%) and somatic mutations with retention of heterozygosity were found in 7 cases (41.2%). Of note was that two mutations resulted in truncated incomplete proteins and one was a point mutation at the consensus site in the conserved ankyrin repeats, which would be crucial for function. Although two-hit inactivation was not evident in any of the mutation cases and further investigation would be needed to elucidate the role of altered p16INK4, these results suggest that the p16INK4 gene mutations are relatively frequent and its inactivation might be important in ampullary carcinogenesis.

Aged↗

Frequent somatic mutations of the APC and p53 genes in sporadic ampullary carcinomas.

Although a close relation of somatic mutations of the adenomatous polyposis coli gene with ampullary carcinomas in familial adenomatous polyposis patients has been reported, the possible association with sporadic ampullary neoplasms has not been fully examined. We have therefore investigated loss of heterozygosity at the adenomatous polyposis coli locus and the mutational status of a portion of the adenomatous polyposis coli gene, including the mutation cluster region, in 17 ampullary carcinomas of non-familial adenomatous polyposis patients. Alteration of the adenomatous polyposis coli gene was found in 8 of 17 (47.1%) cases, as missense or insertion mutations, with or without loss of heterozygosity. Additional investigation of p53 (exons 5-8) and K-ras (codons 12 and 13) gene mutations revealed a striking mutational pattern of the p53 gene. Nine of the 17 cases demonstrated a total of 12 mutations, 6 clustered at codon 189 and 3 at codon 166. Furthermore, 5 of the 12 mutations were nonsense mutations. Regarding the K-ras gene, 4 of the 17 (23.5%) cases had mutations in codon 12, 3 of the 4 cases being derived from the intraduodenal bile duct. The findings indicate that alterations of the adenomatous polyposis coli and the p53 genes are relatively frequent in sporadic ampullary carcinomas. In particular, the clustering at specific p53 codons might offer an etiological clue to clarify ampullary carcinogenesis. Mutations of the K-ras gene, on the other hand, might be characteristic of intraduodenal bile duct origin.

Adenomatous Polyposis Coli↗

An automatic flow controller for a centrifugal blood pump.

To regulate the perfusion flow rate of a centrifugal blood pump, a microcomputer controller was developed. The computer monitored the flow rate of the pump with an electromagnetic flowmeter or an ultrasonic pulse Doppler flowmeter, rotational speed of the pump, aortic pressure, and the amount of blood in a reservoir. A discrete integral controller with a control interval of 1 s was adopted for the controller. For the safety of the control system, we added functions for detecting a clamp on the tubing, a dislocation of the flow sensor, or an inverse direction of the flow sensor. During a standby period, the computer calculated the rotational speed from aortic pressure to minimize the forward or the backward flow at the start of the pump perfusion. The automatic flow controller was used on 5 patients during cardiac operations and maintained the flow rate within +/-6% of the set point.

Algorithms↗

Recombinant interferon-alpha-2a for treatment of chronic hepatitis C: results of a multicenter randomized controlled dose study.

To compare the efficacy of low and relatively high dosages of recombinant interferon (IFN)-alpha-2a in Japanese patients with chronic hepatitis C, as well as to characterize the type of patients who will respond well to a low-dosage treatment, 88 patients with histologically proven chronic hepatitis C were randomly assigned to two treatment groups; one treated with IFN-alpha-2a 6 MU daily for 2 weeks followed by 6 MU three times weekly for 22 weeks (6-MU group), and another given the same initial treatment followed by 3 MU three times weekly for 22 weeks (3-MU group). The rate of sustained normalization of ALT 6 months after the cessation of treatment was 33% in the 3-MU group and 40% in the 6-MU group (p = 0.64). In addition, there was no difference in elimination of serum HCV-RNA 6 months after the cessation of treatment between the 3-MU group (26%) and 6-MU group (29%). Multivariate stepwise regression analysis revealed that serum HCV-RNA level (p = 0.0035) and platelet count (p = 0.0009) were independent variables useful in predicting a sustained response of ALT. The sustained response rate of ALT in patients with a serum HCV-RNA level less than 10(5) copies/ml and serum platelet level above 15 x 10(4)/microliter was 71%, whereas that in patients with a serum HCV-RNA level above 10(5) copies/ml and serum platelet level less than 15 x 10(4)/microliter was 12%. These results indicate that a high rate of sustained response to IFN therapy can be expected in chronic hepatitis C patients with a low serum level of HCV-RNA and a high level of platelets, even if treated with a low dose of IFN.

Antiviral Agents↗

Platelet-associated IgM elevated in patients with chronic hepatitis C contains no anti-platelet autoantibodies.

We investigated whether thrombocytopenia in patients with chronic hepatitis C is due to anti-platelet autoantibodies. Platelet-associated IgG (PAIgG) and platelet-associated IgM (PAIgM) were measured by direct immunofluorescent flow cytometric analysis. Elevation of PAIgM level was detected in 70% of chronic hepatitis C patients, while only a mild elevation of PAIgG level was detected in 32% of the cases. The elevation of PAIgM values in these patients was comparable to that in patients with chronic immune thrombocytopenic purpura (ITP). However, elevated PAIgM was also found in both patients with and without thrombocytopenia, and no correlation was found between PAIgM and platelet count. Eluted PAIgM did not react with normal platelets in all cases with a positive PAIgM value, indicating that eluted PAIgM contained no detectable anti-platelet antibodies. During alpha-interferon therapy, the level of PAIgM increased in association with the decrease in platelet counts in 75% of the cases; however, eluted PAIgM at any day point never reacted with platelets from normal donors. PAIgM was elevated in patients with chronic hepatitis C, but contained no detectable anti-platelet autoantibodies. Thrombocytopenia in these patients is not due to anti-platelet autoantibodies.

Autoantibodies↗

Osmotic flow transients during acetylcholine stimulation in the perfused rat submandibular gland.

Osmotic stress was applied to the perfused rat submandibular gland during steady-state fluid secretion. Alterations of perfusate osmolarity, by addition or withdrawal of sucrose or NaCl, caused transient changes in secretory rate during continuous stimulation with 1 microM acetylcholine (ACh). Hyposmotic perfusates transiently increased, and hyperosmotic perfusates transiently reduced, the secretory rate. The transients were attributed to changes in osmotic flow resulting from changes in the instantaneous transepithelial osmotic gradient. The time course of the change in interstitial osmolarity was determined by using a Cl- electrode to record the changes in interstitial Cl- concentration following a step change in perfusate Cl- concentration. From the calculated changes in interstitial osmolarity and the resulting changes in secretory rate, the osmotic water permeability of the secretory pathway was estimated to be greater than 15.0 +/- 1.2 microliter (mosmol 1-1)-1 min-1 (g wet weight)-1 (9.8 x 10(-6) +/- 0.8 x 10(-6) l atm-1s-1g-1). The transepithelial gradient required to sustain steady state, ACh-evoked secretion would therefore be less than 16 mosmol l-1 NaCl, which is consistent with previous micropuncture data indicating that the luminal fluid is approximately isosmotic.

Acetylcholine↗

Genes encoding farnesyl cysteine carboxyl methyltransferase in Schizosaccharomyces pombe and Xenopus laevis.

The mam4 mutation of Schizosaccharomyces pombe causes mating deficiency in h- cells but not in h+ cells. h- cells defective in mam4 do not secrete active mating pheromone M-factor. We cloned mam4 by complementation. The mam4 gene encodes a protein of 236 amino acids, with several potential membrane-spanning domains, which is 44% identical with farnesyl cysteine carboxyl methyltransferase encoded by STE14 and required for the modification of a-factor in Saccharomyces cerevisiae. Analysis of membrane fractions revealed that mam4 is responsible for the methyltransferase activity in S. pombe. Cells defective in mam4 produced farnesylated but unmethylated cysteine and small peptides but no intact M-factor. These observations strongly suggest that the mam4 gene product is farnesyl cysteine carboxyl methyltransferase that modifies M-factor. Furthermore, transcomplementation of S. pombe mam4 allowed us to isolate an apparent homolog of mam4 from Xenopus laevis (Xmam4). In addition to its sequence similarity to S. pombe mam4, the product of Xmam4 was shown to have a farnesyl cysteine carboxyl methyltransferase activity in S. pombe cells. The isolation of a vertebrate gene encoding farnesyl cysteine carboxyl methyltransferase opens the way to in-depth studies of the role of methylation in a large body of proteins, including Ras superfamily proteins.

Amino Acid Sequence↗

Nocturnal blood pressure fall on ambulatory monitoring in a large international database. The "Ad Hoc' Working Group.

A wide range of definitions is used to distinguish subjects in whom blood pressure (BP) falls at night (dippers) from their counterparts (nondippers). In an attempt to standardize the definition of nondipping, we determined the nocturnal BP fall and night-day BP ratio by 24-hour ambulatory monitoring in 4765 normotensive and 2555 hypertensive subjects from 10 to 99 years old. In all subjects combined, the systolic/diastolic nocturnal fall and corresponding ratio averaged (+/- SD) -16.7 +/- 11.0/ -13.6 +/- 8.1 mm Hg and 87.2 +/- 8.0%/83.1 +/- 9.6%, respectively. In normotensive subjects, the 95th percentiles were -0.3/-1.1 mm Hg for the nocturnal fall and 99.7%/98.3% for the night-day ratio. Both the fall and ratio showed a curvilinear correlation with age. The smallest fall and largest ratio were observed in older (> or = 70 years) subjects. A higher BP on conventional sphygmomanometry was associated with a larger systolic (partial r = .11) and diastolic (r = .12) nocturnal BP fall. The diastolic (r = .08) but not the systolic night-day ratio increased with higher conventional BP. The nocturnal BP fall was larger and the corresponding night-day ratio smaller in oscillometric (n = 5884) than in auscultatory (n = 1436) recordings, in males (n = 3730) than in females (n = 3590), and in Europe (n = 4556) than in the other continents (n = 2764). The distributions of the nocturnal BP fall and night-day ratio showed considerable overlap among normotensive and hypertensive subjects, but the overlap tended to be larger for the ratio than for the fall. Of all subjects, 3.2% had systolic and diastolic ratios of 100% or more. With adjustments applied for confounders, the probability of being a nondipper increased 2.8 times (95% confidence interval, 2.0-4.0) from 30 to 60 years and 5.7 times (4.4-7.4) from 60 to 80 years. The odds ratios were 1.0 (0.8-1.4) for males versus females. 1.6 (1.2-2.1) for subjects with definite hypertension versus normotensive subjects, 2.4 (1.2-4.7) for Asians (n = 2213, 96% Japanese) versus inhabitants of the other continents, and 2.4 (1.5-3.8) for subjects examined with auscultatory versus oscillometric devices. In conclusion, the mathematical definition of nondipping, ie, having a night-day ratio of 100% or more for systolic and diastolic BPs, closely approximated the 95th percentiles of the night-day ratio in normotensive subjects. The ratio depends less on BP level than the nocturnal BP fall and is therefore to be preferred in the definition of dipping status. Notwithstanding the present findings, the reproducibility of nondipping and its prognostic significance need further clarification.

Adolescent↗

Role of nitric oxide in the development of vascular alpha 1-adrenoreceptor desensitization and pressure diuresis in conscious rats.

We evaluated whether a minor impairment of the L-arginine-nitric oxide pathway would affect the desensitization of vascular alpha-adrenoreceptor and pressure diuresis induced by prolonged intravenous infusion of phenylephrine (an alpha-adrenoreceptor agonist) in conscious Wistar-Kyoto rats. We examined dose-pressor-response curves to phenylephrine after an intravenous infusion of phenylephrine (2.5 micrograms.kg-1.min-1) or saline for 9 hours with and without concomitant infusion of N omega-L-arginine methyl ester (L-NAME) given to partially inhibit the L-arginine-nitric oxide pathway. In addition, to evaluate the effect of plasma volume loss on the pressor response to phenylephrine, we evaluated the dose-pressor-response curves to phenylephrine after intravenous injection of furosemide (5 mg/kg) or infusion of phenylephrine (5 micrograms.kg-1.min-1) for 9 hours. The renin-angiotensin, vasopressin and autonomic nervous systems were blocked before the examination of dose-pressor responses. Prolonged infusion of phenylephrine (2.5 micrograms.kg-1.min-1) shifted the dose pressor-response curve to this agent rightward, with significantly increased log ED50 (the dose needed to reach 50% of the maximal response) to a similar extent in both L-NAME-treated (0.51 +/- 0.05 versus 0.93 +/- 0.07 microgram/kg) and -untreated (0.79 +/- 0.06 versus 1.08 +/- 0.03 micrograms/kg) rats. The log ED50 value after phenylephrine infusion (5 micrograms.kg-1.min-1) was significantly higher than that after furosemide injection (1.28 +/- 0.06 versus 1.02 +/- 0.01 micrograms/kg, respectively, P < .01), although the two treatments induced a similar loss of plasma volume. The slope in the linear relationship between the average change in mean arterial pressure during the 9-hour infusion period and the rate of urine excretion was significantly depressed in L-NAME-treated versus control rats (L-NAME: 0.057 mL.kg-1.h-1.mm Hg-1, control: 0.146 mL.kg-1.h-1.mm Hg-1, P < .05). In conclusion, a minor impairment of the L-arginine-nitric oxide pathway does not appear to interfere with the desensitization of vascular alpha-adrenoreceptor but does inhibit the pressure-diuresis response in conscious normotensive rats.

Analysis of Variance↗

Expression of variant forms of insulin receptor substrate-1 identified in patients with noninsulin-dependent diabetes mellitus.

Several polymorphisms have been identified in the amino acid sequence of human insulin receptor substrate-1 (IRS-1). Some of the variant sequences have been reported to be increased in prevalence among patients with noninsulin-dependent diabetes mellitus (NIDDM). This observation led to the hypothesis that these amino acid substitutions may impair the function of IRS-1, thereby causing the insulin resistance seen in patients with NIDDM. To address this question, we have designed studies to evaluate the effects of three variant sequences identified in our laboratory: Gly819-->Arg, Gly972-->Arg, and Arg1221-->Cys. We constructed four IRS-1 expression vectors for transfection in COS-7 cells: wild-type, single mutant (Gly819-->Arg), double mutant (Gly819-->Arg; Gly972-->Arg), and triple mutant (Gly819-->Arg; Gly972-->Arg; Arg1221-->Cys) IRS-1. The mutations did not alter the level of expression or the extent of insulin receptor-mediated tyrosine phosphorylation of recombinant IRS-1. Moreover, the mutations did not lead to a detectable impairment in the association of recombinant IRS-1 with important downstream effectors, including the p85 subunit of phosphatidylinositol 3-kinase and growth factor receptor-binding protein-2. We conclude that these amino acid substitutions do not appear to cause a major defect in the function of IRS-1, as judged by our assays. However, this type of assay probably lacks the sensitivity to detect subtle functional defects. In light of the suggestive associations observed in epidemiological studies, it is premature to totally discard the hypothesis that variant sequences of IRS-1 may contribute to the pathogenesis of NIDDM. Nevertheless, our studies cannot be interpreted as lending support to that hypothesis.

Adaptor Proteins, Signal Transducing↗

Predictive value of home blood pressure measurement in relation to stroke morbidity: a population-based pilot study in Ohasama, Japan.

We investigated the utility of home blood pressure measurements for determining the risk of stroke. We also analyzed the relationship between home blood pressure and the incidence of stroke. Home blood pressure and screening blood pressure measurements were obtained from 1,789 residents (aged 40 yr or older) of a rural Japanese community. Blood pressure was measured at home with a semiautomatic device. A mean (+/-SD) of 23.0 +/- 7.5 measurements were made for each subject. Subjects without a history of stroke and who were not receiving medication for hypertension (n = 1,256) were prospectively followed up for 4.4 +/- 2.1 yr. Subjects were subdivided into quintiles according to their baseline blood pressure. The association between the baseline blood pressure and the incidence of the first-ever stroke was examined with the Cox proportional hazards regression model, adjusted for age and sex. The lowest risk of stroke morbidity occurred in the subjects in the third quintile for home systolic blood pressure (117-123 mmHg) and in those in the second quintile for home diastolic blood pressure (66-70 mmHg). The subjects in the fifth quintiles for home systolic (> or = 133 mmHg) and diastolic blood pressure (> or = 81 mmHg) had a significantly increased risk of stroke morbidity. The subjects in the first and the second quintiles for home systolic blood pressure and those in the first quintile for home diastolic blood pressure tended to have an increased risk as compared with subjects in the lowest risk groups, although this increase was not statistically significant, indicating two possibilities: a trend toward a J-shaped relationship or no-decrease in risk of the first-ever stroke in subjects with home blood pressure level less than 123/70 mmHg. This relationship was not observed for screening blood pressure. We conclude that home blood pressure measurements can provide additional prognostic information to that obtained from blood pressure measurement in a medical environment.

Adult↗

Monoclonal antibodies against pig ovarian follicular granulosa cells induce apoptotic cell death in cultured granulosa cells.

Two monoclonal antibodies capable of inducing granulosa cell apoptosis were produced against granulosa cells prepared from antral follicles of pig ovaries. The healthy follicles, 4-5 mm in diameter, were dissected from the ovaries of gilts, and then granulosa cells were isolated. BALB/c female mice were immunized with the isolated granulosa cells. Antibodies against the granulosa cells were detected by immunofluorescent staining using frozen ovarian sections. The isolated spleen cells prepared from immunized mice producing antibodies against the granulosa cells were fused with Sp2/O-Ag 14 mouse myeloma cells by standard hybridization techniques. Two hybridoma clones, PFG-1 and PFG-2, which produced specific IgM antibodies against granulosa cells were selected. Western blotting analysis revealed that PFG-1 and PFG-2 antibodies specifically recognized cell-membrane proteins with molecular weights of 55 and 70 kD and isoelectric points of 5.9 and 5.4, respectively. The monoclonal antibodies immunohistochemically reacted with granulosa cells of healthy follicles. When the isolated granulosa cells prepared from healthy follicles were cultured in medium containing 0.1 or 10 micrograms/m/PFG-1 or PFG-2 antibodies, respectively, the cells underwent apoptosis as determined by nuclear morphology, DNA electrophoresis and flow cytometric analysis. In conclusion, these two monoclonal antibodies against granulosa cells have cell-killing activity in cultured granulosa cells.

Animals↗

Nutritional evaluation of women in urban and rural areas in Korea as studied by total food duplicate method.

Nutrient intake was studied by the total food duplicate method in 141 adult working women (at the ages of 21 to 56 years) in four regions (Seoul, Pusan, Chunan and Haman) in Korea. Clinical, hematological and anthropometrical examinations were conducted in parallel. The nutrient intakes were estimated in reference to the weight of each food item and the national standard food composition tables for Korean population, and evaluated in comparison with the nationally recommended dietary allowances (RDA). The intakes were essentially sufficient when evaluated on a group basis. Plant-based foods were major sources of both protein (67%) and lipid (72%). Dinner was the most substantial sources of all nutrients. Further evaluation on an individual basis taking 80-120% RDA as acceptable showed that young people (at the ages of 20-29 years) and those in Seoul had highest prevalence of insufficient intake of nutrients, especially energy, protein and iron. Consumption of rice, the traditional staple food, was the lowest in Seoul and in the youngest groups as compared with others. The prevalence of overweight cases was also the lowest in the Seoul participants. The two observations when combined apparently suggest the difficulties in public nutrition.

Adult↗

Determinants of circadian blood pressure variation: a community-based study in Ohasama.

We investigated factors affecting the nocturnal decline in blood pressure (BP). A cross sectional study was done in 706 community-based untreated subjects > or = 20 years of age. Screening and ambulatory BPs were measured and the effects of age and the ambulatory BP on the nocturnal decline were examined. Bivariate analysis demonstrated that the magnitude of the decline and the percent decline in the nocturnal BP increased with increase in daytime ambulatory BP and decreased with increase in nighttime ambulatory BP. Although the magnitude of the nocturnal decline in BP increased with increasing daytime BP, the nocturnal BP in hypertensives was still higher than those in normotensives. The magnitude decreased with increasing age in men but not in women, while the percent decline decreased with increasing age in both men and women. Since bivariate analysis demonstrated that the daytime BP, nighttime BP, and standard deviation of the 24-hour BP strongly correlated with the magnitude of the nocturnal decline, these parameters were excluded as independent variables from the multivariate analysis. In the multivariate analysis the nighttime pulse pressure was negatively and daytime pulse pressure was positively associated with the magnitude of the decline and the percent decline in the nocturnal BP. A non-dipping circadian variation was frequently observed in elderly normotensive men but the rate of nondipper was rather low in hypertensive individuals in the general population. A marked dipping pattern was frequently observed in hypertensive women > or = 70 years of age. The nocturnal BP levels in subjects with daytime hypertension are higher than those in subjects with daytime normotension. Therefore, BP must ideally be lowered over 24-hour period in hypertensive subjects. The diminished magnitude of the decline and the decrease in the percent decline in the nocturnal BP in the elderly may be mediated by the disturbed baroreflex function due to the decrease in compliance of large elastic artery. However, in some elderly hypertensive women, excess nocturnal decline in BP is observed. In such subjects, we should take care of the nocturnal BP levels during treatment.

Adult↗

Three cases of Gitelman's syndrome possibly caused by different mutations in the thiazide-sensitive Na-Cl cotransporter.

Three adult Japanese cases of Gitelman's syndrome were characterized by secondary aldosteronism, hypokalemic alkalosis, hypomagnesemia, and hypocalciuria. Two were revealed to be familial cases. A mutation in the thiazide-sensitive Na-Cl cotransporter gene, which had already been confirmed in one family (Takeuchi et al. J Clin Endocrinol Metab 81: 4496,1996), was not detected in the other two cases. These observations may possibly support the previous report (Simon et al. Nature Genet 12: 24, 1996) that Gitelman's syndrome is caused by a variety of mutations in the thiazide-sensitive Na-Cl cotransporter.

Aged↗