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Biomedical subjects

K Kozaki

Publications and source records attributed to K Kozaki.

At least 91 records · Page 5Linked to original sources

Augmented contractile function and abnormal Ca2+ handling in the aorta of Zucker obese rats with insulin resistance.

To investigate the role of hyperinsulinemia/insulin resistance in vasomotor tone regulation, we studied the effects of vasoactive substances on tension and intracellular free calcium concentration ([Ca2+]i) of aortic smooth muscle derived from rats that were made hyperinsulinemic by insulin infusion and from Zucker obese rats with insulin resistance. The tension and [Ca2+]i of fura 2-loaded aortic strip preparations without endothelium were simultaneously measured by using a fluorimeter. Ten male Wistar rats received a continuous subcutaneous infusion of insulin (18 nmol x kg(-1) x day(-1)) for 2 weeks with osmotic minipumps (INS group). A control group of 10 rats received vehicle. The plasma immunoreactive insulin concentration in the INS group increased to 930 +/- 54 pmol/l. The increase in [Ca2+]i and tension by KCl and phenylephrine (PE) were lower in the INS group without alteration of the [Ca2+]i-tension relationship. The responses to serotonin (5-HT) in the INS group were similar to those in the control group. In contrast, responses to KCl, PE and 5-HT were markedly enhanced in Zucker obese rats compared with those in Zucker lean rats. The pretreatment of aortic preparations from lean rats with Bay K8644 significantly enhanced the responses to KCl to the level observed in the preparations from obese rats; however, Bay K 8644 failed to affect the responses to KCl in obese rats. These results suggest that enhanced vascular contractile responses to vasoactive substances, possibly due to altered function of the voltage-dependent Ca2+ channel in vascular smooth muscle, may play an important role in the pathogenesis of hypertension in the insulin resistance syndrome.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

[Use of a micturition-monitoring device in elderly inpatients].

More than 100,000 people suffer from functional urinary incontinence in Japan. To improve the quality of life of these people, we tested a device for monitoring micturition by means of a thin-layer membrane sensor in a diaper. The device was tested in elderly inpatients, and associated changes in the wordload of the nursing staff were also recorded. The device was beneficial because the precise micturition time was easily obtained and thus the daily pattern of micturition became obvious. With the use of this device, the time during which the patients wore wet diapers was shorter than with the conventional system of scheduled changes. However, the increase in the frequency of diaper changed doubled the workload of the nursing staff. In conclusion, improving the quality of life with regard to urinary incontinence entails an increase in the workload of the nursing staff; efficient distribution of that work may require some staff members to devote all their time to changing diapers.

Aged↗

Effects of estrogen on atherosclerosis formation and serum nitrite/nitrate concentrations in cholesterol-fed ovariectomized rabbits.

This study was to examine the effects of estrogen replacement on atherosclerosis formation in ovariectomized cholesterol-fed rabbits. We also examined serum levels of nitrite/nitrate, stable metabolites of nitric oxide, to investigate the involvement of nitric oxide. Female New Zealand White rabbits were ovariectomized and divided into 3 groups; 1) fed a normal diet (ND group, n=5), 2) fed a 1% cholesterol diet (CD group, n=6), or 3) fed a 1% cholesterol diet and received estrogen replacement (CD+E group, n=7). After 3 months, the rabbits were sacrificed to examine atherosclerosis formation. Atherosclerosis was not observed in ND. The oil red 0 positive area in the aorta was significantly greater in CD than in CD+E (CD, 17.3+/-2.2; CD+E, 9.3+/-0.8%, p<0.05). Stenosis of the coronary artery was also significantly greater in CD than in CD+E (CD, 30.6+/-9.7; CD+E, 6.7+/-2.9%, p <0.05). There was no significant difference in serum lipids between CD and CD+E. Serum nitrite/nitrate levels were significantly lower in CD than in ND (ND, 37.6+/-3.6; CD, 25.3+/-3.1 microM, p<0.05). There was a non-significant trend towards higher nitrite/nitrate levels after estrogen replacement (CD+E, 34.4+/-3.8 microM, p=0.08 vs. CD). These results suggest that direct actions on vascular wall including nitric oxide production contribute to the anti-atherogenic effects of estrogen.

Animals↗

Modulation of endothelium-dependent flow-mediated dilatation of the brachial artery by sex and menstrual cycle.

BACKGROUND: Estrogen has been reported to augment endothelium-dependent vasodilatation. The role of endogenous ovarian hormones in modulating endothelium-dependent vasodilatation, however, remains to be determined. The purpose of the present study was to investigate the effects of sex and menstrual cycle on endothelium-dependent flow-mediated vasodilatation. METHODS AND RESULTS: Seventeen female volunteers 25.1 +/- 0.8 years old and 17 age-matched male volunteers were examined. We measured brachial artery diameters noninvasively using a 7.5-MHz ultrasound machine at rest, during reactive hyperemia, and after sublingual nitroglycerin administration. All female subjects were studied three times each, in three different phases of one menstrual cycle (M, menstrual phase; F, follicular phase; and L, luteal phase). Flow-mediated diameter (D) increase (%FMD; delta D/D x 100) in M, when serum estradiol level was low (121.9 +/- 12.5 pmol/L), was 11.22 +/- 0.58%, and the value was comparable to that in male subjects (10.60 +/- 0.75%). %FMD increased in F (18.20 +/- 0.81%, P < .01 versus M) and L (17.53 +/- 0.74%, P < .01 versus M), when serum estradiol level was high (F, 632.0 +/- 74.5 and L, 533.8 +/- 33.4 pmol/L, P < .01 versus M). Endothelium-independent vasodilatation by nitroglycerin increased in both F and L. However, the increment was smaller than that of %FMD. CONCLUSIONS: Endothelium-dependent vasodilatation varies during the menstrual cycle. The endogenous estradiol may be involved in this menstrual cycle-related vasodilatation.

Adult↗

Age-related alteration of proline hydroxylase and collagen-binding heat shock protein (HSP47) expression in human fibroblasts.

Changes in the expression of alpha and beta subunits of proline 4-hydroxylase (PH alpha and PH beta) and HSP47, implicated as a molecular chaperone specific for procollagen processing, were examined in human embryonal fibroblasts in relation to in vitro aging. For this purpose a model with treatments causing the decreased hydroxylation of proline residues in procollagens was used. In cells at a low population doubling level (PDL) induction of PH alpha, PH beta, and HSP47 by depletion of ascorbate or addition of alpha-alpha' dipyridyl could be clearly demonstrated by immunoprecipitation and Northern blotting. In contrast, the induction of PH alpha and HSP47 expression was markedly attenuated in high PDL cells, indicating an age-related decrease in response to procollagen retention in the ER caused by hypohydroxylation of proline residues of procollagens.

Animals↗

Age-related attenuation of HSP47 heat response in fibroblasts.

The collagen-binding heat shock protein of molecular weight 47,000 (HSP47), resident in the endoplasmic reticulum (ER), is assumed to play a specific role as a molecular chaperon in the processing of procollagen molecules. The present investigation of age-related alteration in the HSP47 heat response in cultured murine and human fibroblasts revealed expression in cells with a low population doubling level (PDL) derived from young mice and people more inducible by heat treatment than those from older mice and people. On the other hand, cells with a high PDL showed a very low heat response in terms of HSP47 expression regardless of the donor age. Northern blot analysis of HSP47 m-RNA indicated that the age related attenuation of HSP47 expression was regulated by transcriptional mechanisms. Furthermore, immunofluorescent analysis using a monoclonal antibody against the carboxylterminal propeptide of type I procollagen revealed far greater retention of procollagen molecules in the ER lumen of cells from old persons than in those from young persons. This was particularly prominent in heat-treated cells from old persons, indicating the possibility that the observed decrease in HSP47 heat response might cause blockage of procollagen transport to the Golgi and therefore secretion.

Aging↗

Age-related decrease in the effect of parathyroid hormone-related protein on cytosolic free calcium level and tension in rat aortic smooth muscle.

Age-related changes in the effect of parathyroid hormone-related protein (PTHrP) on the cytosolic free calcium level ([Ca2+]i) and on the tension in rat aortic smooth muscle were investigated. The possible involvement of cAMP, a second messenger of PTHrP, in such changes was also investigated. Spiral aortic strip preparations without endothelium from 8-weeks, 6-months, and 24-months old rats were treated with fura 2/AM, and the fluorescence ratio R340/380, an index of [Ca2+]i was measured. Simultaneously, the tension of the preparations was measured. PTHrP-(1-34) and dibutyryl cAMP produced concentration-dependent decreases in the tension and in R340/380 in aortas precontracted with phenylephrine (10(-7) M). These effects were significantly lower in the aortas of 24-months old rats than in the vessels of 8-weeks and 6-months old rats. The effects were similar in the aortas of 8-weeks and 6-months old rats. PTHrP-(1-34) concentration-dependently increased cAMP production in vascular smooth muscle cells (VSMCs) from 8-weeks old rats. However, the increase in cAMP production was significantly lower in cultured VSMCs from 6-months and 24-months old rats than in cells from 8-weeks old rats. These results suggest that the reduced cAMP production stimulated by PTHrP and the reduced effects of cAMP with aging might contribute to the age-related changes in the decreases in tension and [Ca2+]i in response to PTHrP in the rat aorta.

Age Factors↗

Improved skin blood flow and cutaneous temperature in the foot of a patient with arteriosclerosis obliterans by vasopressin V1 antagonist (OPC21268). A case report.

A seventy-four-year-old woman with arteriosclerosis obliterans, diabetes mellitus, and hypertension was admitted for the treatment of intermittent claudication and coldness and pain in the right lower extremity. After the administration of a vasopressin V1 antagonist, OPC21268, the symptoms were markedly improved. Furthermore, blood flow in the dorsalis pedis artery and the cutaneous temperature in the right foot increased in response to acute and chronic administration of OPC21268. OPC21268 may be a new useful therapeutic tool for the treatment of arteriosclerosis obliterans.

Aged↗

[A case of pulmonary infiltration with eosinophilia (PIE) syndrome associated with syndrome of inappropriate secretion of ADH (SIADH) in the elderly patient].

A 76-year-old woman was admitted to our hospital because of productive cough, fever and anorexia in January 1995. She had suffered from bronchial asthma for 25 years. From 1983, exacerbation of PIE was recorded three times, on which occasions prednisolone and antibiotics were quite effective. On admission, marked leukocytosis (28,000/microliters) and eosinophilia (18,000/microliters) were found. However, plasma IgE level was normal, and specific antigen for eosinophilia was not detected by RAST or the skin allergic reaction test. Chest X-ray film and CT scan revealed extensive bilateral pulmonary infiltration. Increase in eosinophils (33%) was demonstrated in bronchoalveolar lavage. Furthermore, biopsy specimen of the affected lung revealed diffuse infiltration of eosinophils into alveolar septa. On the basis of these findings, the patient was diagnosed as chronic eosinophilic pneumonia (PIE syndrome). Hyponatremia (117 mEq/l) was persistent after the hydration with normal saline. Plasma ADH was not suppressed (2.29 pg/ml) in spite of hypoosmolality of plasma. Laboratory examination showed that renal, adrenal and thyroid function as well as plasma renin activity were normal. Taking these findings together, she was diagnosed as having SIADH. Treatment with prednisolone improved not only the PIE syndrome but also SIADH.

Aged↗

[Nocturnal pulmonary hypertension in an elderly patient with sleep apnea syndrome].

We report a case of sleep apnea syndrome (SAS) with nocturnal pulmonary hypertension (NPH) in a 71-year-old man suffering from dyspnea during sleep. Severe snoring at night and daytime sleepiness were noticed before admission by his wife. Nocturnal oxygen desaturation (NOD) was documented with a pulse oximeter and severe sleep apnea syndrome was diagnosed on the basis of results of respiratory inductive plethysmography, an apnea index (AI) > 20, minimum SpO2 56%. NPH was diagnosed by Swan-Ganz catheter. The levels of NPH were severe. Elevation of systolic pulmonary arterial pressure (PAP) above 40 mmHg was observed 137 episodes at night. Both NPH and NOD were improved by 1 L/min of nasal oxygen therapy. A number of episodes of systolic PAP above 40 mmHg with oxygen therapy was 55 episodes. Peak mean PAP was 36 mmHg in room air vs 33 mmHg in oxygen therapy. Minimum SpO2 with oxygen therapy was improved to 69%. Total time of SpO2 < 90% at night was 153 minutes in room air vs 37 minutes in oxygen therapy. In this case, NPH and NOD due to severe SAS were remarkably improved by oxygen therapy.

Aged↗