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Biomedical subjects

M Eto

Publications and source records attributed to M Eto.

At least 109 records · Page 6Linked to original sources
PubMed1996

[Guidelines on treatment of hypertension in the elderly, 1995--a tentative plan for comprehensive research projects on aging and health-- Members of the Research Group for "Guidelines on Treatment of Hypertension in the Elderly", Comprehensive Research Projects on Aging and Health, the Ministry of Health and Welfare of Japan].

We propose the following guidelines for treatment of hypertension in the elderly. 1. Indications for Treatment. 1) Age: Lifestyle modification is recommended for patients aged 85 years and older. Antihypertensive therapy should be limited to patients in whom the merit of the treatment is obvious. 2) Blood pressure: Systolic BP > 160 mmHg, diastolic BP > 90 approximately 10 mmHg. Systolic BP < age + 100 mmHg for those aged 70 years and older. Patients with mild hypertension (140-160/ 90-95 mmHg) associated with cardiovascular disease should be considered for antihypertensive drug therapy. 2. Goal of Therapy for BP: The goal BP in elderly patients is higher than that in younger patients (BP reduction of 10-20 mmHg for systolic BP and 5-10 mmHg for diastolic BP). In general, 140-160/< 90 mmHg is recommended as the goal. However, lowering the BP below 150/85 should be done with caution. 3. Rate of Lowering BP: Start with half the usual dose, observe at the same dose for at least four weeks, and reach the target BP over two months. Increasing the dose of antihypertensive drugs should be done very slowly. 4. Lifestyle Modification: 1) Dietary modification: (1) Reduction of sodium intake is highly effective in elderly patients due to their high salt-sensitivity. NaCl intake of less than 10 g/day is recommended. Serum Na+ should be occasionally measured. (2) Potassium supplementation is recommended, but with caution in patients with renal insufficiency. (3) Sufficient intake of calcium and magnesium is recommended. (4) Reduce saturated fatty acids. Intake of fish is recommended. (2) Regular physical activity: Recommended exercise for patients aged 60 years and older: peak heart rate 110/minute, for 30-40 minutes a day, 3-5 days a week. (3) Weight reduction. (4) Moderation of alcohol intake, smoking cessation. 5. Pharmacologic Treatment: 1) Initial drug therapy. First choice: Long-acting (once or twice a day) Ca antagonists or ACE inhibitors. Second choice: Thiazide diuretics (combined with potassium-sparing diuretic). 2) Combination therapy. (1) For patients without complications, either of the following is recommended. i) Ca antagoinst + ACE inhibitor, ii) ACE inhibitor + Ca antagonist (or low-dose diuretics), iii) diuretic + Ca antagonist (or ACE inhibitor), iv) beta-blockers, alpha 1-blockers, alpha + beta blockers can be used according to the patho-physiological state of the patient. (2) For patients with complications. Drug(s) should be selected according to each complication. 3) Relatively contraindicated drugs. beta-Blockers and alpha 1-blockers are relatively contraindicated in elderly patients with hypertension in Japan. Centrally acting agents such as reserpine, methyldopa and clonidine are also relatively contraindicated beta-Blockers are contraindicated in patients with congestive heart failure, arteriosclerosis obliterans, chronic obstructive pulmonary disease, diabetes mellitus (or glucose intolerance), or bradycardia. These conditions are often present in elderly subjects. Elderly subjects are susceptible to alpha 1-blocker-induced orthostatic hypotension, since their baroreceptor reflex is diminished. Orthostatic hypotension may cause falls and bone fractures in the elderly.

Aged↗
PubMed1996

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↗
PubMed1996

Remnant-like particles (RLP) from NIDDM patients with apolipoprotein E3/3 phenotype stimulate cholesteryl ester synthesis in human monocyte-derived macrophages.

We tested the ability of remnant-like particles (RLP) from NIDDM patients to stimulate cholesteryl ester synthesis in human monocyte-derived macrophages. Six NIDDM patients were studied together with 7 non-diabetic subjects. All had apolipoprotein (apo) E3/3 phenotype. RLP were isolated using an immunoaffinity gel mixture of anti apo B-100 and anti apo A-1 monoclonal antibodies coupled to Sepharose 4B. Plasma levels of triglyceride, total cholesterol (chol) and high density lipoprotein-chol were not statistically different, but plasma levels of RLP-chol were significantly (p < 0.05) higher in NIDDM patients (10.5 +/- 2.2 mg/dl) than in non-diabetic controls (5.0 +/- 1.7 mg/dl). The effects of RLP from NIDDM patients on macrophage cholesteryl ester synthesis were estimated. 14C-oleate incorporation into cholesteryl esters in macrophages was significantly (p < 0.01) higher in NIDDM patients with apo E3/3 (0.326 +/- 0.037 nmole/mg cell protein) than in non-diabetic controls with apo E3/3 (0.181 +/- 0.011 nmole/ mg cell protein). It is suggested that RLP from NIDDM play a role in the accumulation of cholesteryl esters and are one of the risk factors for the acceleration of atherosclerosis in NIDDM.

Antibodies, Monoclonal↗
PubMed1995

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↗
PubMed1995

Rapid gastric emptying and pathological changes of vagus nerve in the spontaneously diabetic Chinese hamster.

To estimate autonomic neuropathy in the spontaneously diabetic Chinese hamster, which is an established strain for the non-obese non-insulin-dependent diabetes mellitus model, gastric emptying and morphometric analysis of the vagus nerve were studied in 12-month-old spontaneously diabetic Chinese hamsters (duration of diabetes was 9 months). Gastric emptying was determined by the phenol red method. Vagus was obtained from just above the diaphragm. Morphometric analysis of myelinated fibers was performed light-microscopically using semi-thin sections and unmyelinated fibers were studied electron-microscopically using ultra-thin sections. Gastric emptying of spontaneously diabetic Chinese hamster was significantly increased compared with control (86.6 +/- 1.9 vs. 51.2 +/- 3.4, P < 0.01). Myelinated fibers of the spontaneously diabetic Chinese hamster were not different from control animals, while the size of unmyelinated fibers in the spontaneously diabetic Chinese hamster was significantly decreased. These data suggest that pathological changes in unmyelinated fibers, which consist mainly of afferent fibers, might play a role in gastric motor dysfunction in the spontaneously diabetic Chinese hamster.

Animals↗
PubMed1995

The induction of skin xenograft tolerance in rat-to-mouse combination could be affected by DFR mediating cells and antibodies against rat bone marrow cells as well as NK cells in the cyclophosphamide-induced tolerance system.

We investigated whether the prolongation of skin xenograft survival was obtained by a tolerance-inducing method using cyclophosphamide (CY), by which long-lasting skin allograft tolerance could be induced. The long-lasting skin allograft survival could be obtained in the recipient C3H/HeN (C3H) mice which were given 100 micrograms of anti-CD4 mAb on day -3, 1 x 10(8) spleen cells (SC) plus 3 x 10(7) bone marrow cells (BMC) derived from C57BL/6 (B6) mice on day -2,200 mg/kg CY on day 0, and which were grafted with allogeneic B6 skin on day 14. When the C3H mice were treated with anti-CD4 mAb, 1 x 10(8) s.c. plus 5 x 10(7) BMC derived from F344 rat and CY, the F344 skin grafts survived slightly longer (about 15 days) than those in untreated recipients (about 8.4 days). Such a prolongation of skin xenograft survival was considered donor-specific because rejection of 3rd party skin grafts from BN rats occurred significantly earlier than that of F344 skin grafts. In the recipient C3H mice treated with anti-CD4 mAb, F344 s.c. plus BMC and CY, mixed chimerism in the periphery was detected for a few days after CY administration, although intrathymic chimerism was not detected throughout this study. In these recipient C3H mice, cytotoxic T lymphocytes (CTL) against F344 antigens were completely abrogated through the delayed footpad reaction (DFR) remained at a low but significant level. Moreover, though antibody (Ab) activity against F344 s.c. was completely abrogated, neither Ab activity against F344 BMC, which seemed to have a background common to natural Ab activity, nor NK activity were abrogated by this treatment. These results suggested that DFR mediating cells directly mediated skin xenograft rejection in the recipient mice treated with anti-CD4 mAb, F344 cells, and CY. Such cells may interfere with establishment of mixed chimerism and long-lasting skin xenograft tolerance, presumably in cooperation with CY-resistant Ab activity and NK cells.

Animals↗
PubMed1995

A novel protein phosphatase-1 inhibitory protein potentiated by protein kinase C. Isolation from porcine aorta media and characterization.

A novel phosphorylation-dependent inhibitory protein (IP) of porcine aorta myosin light chain phosphatase (PA-MLCP) was purified to homogeneity from porcine aorta media. The molecular mass of IP was 20 kDa. IP phosphorylated by endogenous potentiating kinase (IP-K) inhibited not only PA-MLCP activity, but also that of the catalytic subunit of protein phosphatase-1. The amino acid sequence of a peptide derived from IP phosphorylated with IP-K, RHARVT*VK, shared one of the consensus sequences phosphorylatable by protein kinase C (PKC), where T* was phosphorylated. IP was phosphorylated by PKC and the phosphorylated product inhibited PA-MLCP as strongly as IP phosphorylated with IP-K.

Amino Acid Sequence↗
PubMed1995

Increased frequency of apolipoprotein epsilon 2 allele in non-insulin dependent diabetic (NIDDM) patients with nephropathy.

The genetic polymorphism of apolipoprotein E (epsilon 2, epsilon 3 and epsilon 4) is associated with lipid abnormalities. It has been suggested that lipid abnormalities may contribute to the development and progression of kidney diseases, including diabetic nephropathy. Thus, in this study we compared the apo E allele frequencies among 146 non-insulin-dependent diabetic (NIDDM) patients with nephropathy, 135 NIDDM patients without nephropathy and 576 of the general Japanese population. The epsilon 2 allele frequency was significantly higher in diabetic patients with nephropathy (7.2%) and with renal failure (9.7%) than in diabetic patients without nephropathy (2.6%) and in the general Japanese population (3.7%). It is concluded that there is a possibility that the epsilon 2 allele is associated with nephropathy in NIDDM.

Alleles↗
PubMed1995

[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↗
PubMed1995

Prolongation of kidney graft survival by cyclophosphamide-induced tolerance in rats.

In this study, we have extended a cyclophosphamide (CP)-induced tolerance system to kidney transplantation in rats to examine whether or not we can overcome fully allogeneic (major histocompatibility complex plus minor histocompatibility) antigen barriers in organ transplantation. In the recipient Lewis (LEW, RT1(1)) rats that were primed intravenously with 4 x 10(8) spleen cells plus 2 x 10(8) bone marrow cells from Brown-Norway (BN, RT1n) rats and treated intraperitoneally with 100 mg./kg. of cyclophosphamide (CP) 2 days later, the survival of kidney allografts, but not skin allografts, from BN was prolonged as compared with that in the untreated LEW rats. Some of the kidney allografts survived for more than 100 days without further immunosuppressants. The tolerant state induced was tolerogen specific, and the suppression of tissue damage of the grafted kidney in such tolerant rats was also confirmed by the histopathological findings of the grafted kidney. These results indicate that considerable levels of tolerance can be induced, at least in organ transplantation, across fully allogeneic antigen barriers in rats by a CP-induced tolerance system. We believe that the present study is the first step in applying our CP-induced tolerance system using skin grafting in the murine model to clinical organ transplantation.

Animals↗
PubMed1994

Amelioration of acute graft-versus-host disease and re-establishment of tolerance by short-term treatment with an anti-TCR antibody.

We investigated whether tolerance can be re-established in mice with graft-vs-host disease (GVHD) by using a short-term, T cell-depleting treatment with an anti-TCR-alpha beta mAb. GVHD was induced in 950-rad-irradiated AKR mice (H-2k, Mls-1a) by injecting 5 x 10(6) T cell-depleted bone marrow cells together with either 10(7) or 2 x 10(6) lymph node (LN) cells from BALB/c mice (H-2d, and Mls-1b). AKR mice that received 10(7) LN cells exhibited a severe form of acute GVHD, in which all mice died by day 60. In this severe form of GVHD, treatment with anti-TCR-alpha beta mAb completely ameliorated the induction of GVHD when initiated on day 0 (a total of 800 micrograms/mouse administered on days 0,5, and 10). When the same protocol was begun on day 10, it had no therapeutic effect. However, this delayed treatment with anti-TCR-alpha beta mAb was very effective in reversing a less severe form of GVHD that was induced by the injection of 2 x 10(6) donor LN cells. Recipient mice given prophylactic anti-TCR-alpha beta treatment achieved host-specific tolerance in association with clonal deletion of host Mls-1a-reactive V beta 6+ T cells. In contrast, spleen cells from recipient mice that recovered from the mild form of GVHD as a result of the delayed anti-TCR-alpha beta treatment contained a considerable proportion of the V beta 6+ T cells, despite the healthy appearance of these mice. A MLR assay revealed that the spleen cells from these mice responded well to Mls-1a Ag but not to H-2k Ag, in contrast with the apparent responses of spleen cells from untreated GVHD controls to both Ags. In addition, cells from the anti-TCR-alpha beta-treated mice exhibited a specific reduction in cytotoxicity against AKR blasts. Collectively, these data indicate that a short-term treatment of mice having GVHD with an anti-TCR-alpha beta mAb, starting even after disease onset, can re-establish host-specific tolerance, at least to the host-histo-compatibility Ag.

Acute Disease↗
PubMed1994

Exacerbation of established collagen-induced arthritis in mice treated with an anti-T cell receptor antibody.

OBJECTIVE: To investigate the effect of T cell depletion on established collagen-induced arthritis (CIA) in mice, using monoclonal antibodies (MAb) to T cell receptor alpha/beta (TCR alpha/beta). In addition, experiments using anti-CD3 MAb were performed for comparison. METHODS: CIA was induced in male DBA/1 mice by immunizing them twice with bovine type II collagen (CII). The arthritis score and anti-CII antibody titers were examined serially. Proportions of T cells were determined by fluorescence-activated cell sorter (FACS) analysis on spleen cells or peripheral blood cells. RESULTS: When anti-TCR alpha/beta MAb was injected on the day of CII priming, no arthritis was detected in association with depressed anti-CII antibody titers. Unexpectedly, however, when MAb was given after arthritis was established, a rapid exacerbation of arthritis was observed, which resulted in ankylosis of most joints. Anti-CII antibody titers were not affected. The addition of anti-TCR gamma/delta MAb had no effect on the augmented arthritis. T cell depletion by anti-CD3 MAb during established CIA also caused an enhancement of arthritis, which was, however, weak and only transient. FACS analysis revealed that the early improvement of arthritis after the transient augmentation seen in the mice treated with anti-CD3 MAb paralleled the early recovery of alpha/beta T cells in the periphery. CONCLUSION: The present results support the concept that alpha/beta T cells, in general, may play a regulatory role in the clinical course of murine CIA after disease onset. Therefore, caution is recommended when using intensive T cell-targeted therapy in patients with rheumatoid arthritis.

Animals↗
PubMed1994

Multicystic aneurysmal dilatation of bilateral coronary artery fistula.

Bilateral coronary artery fistula constitutes an uncommon subgroup of coronary artery fistulas that may have a distinct embryologic origin. Coronary artery fistulas usually show a tortuous arrangement upon coronary angiography, but aneurysmal dilatation is rare. We report here an extremely rare case of coronary artery fistula originating from both coronary arteries, which showed multicystic aneurysmal dilatation.

Aged↗
PubMed1994

Apolipoprotein E2, renal failure and lipid abnormalities in non-insulin-dependent diabetes mellitus.

The association of apolipoprotein E (apo E) genetic polymorphism, particularly apo E2, with renal failure (plasma creatinine > or = 1.4 mg/dl, and urinary albumin excretion index > or = 300 mg/g.creatinine and/or persistent proteinuria) was investigated in 57 non-insulin-dependent diabetic (NIDDM) patients. Apo E2 allele frequency was significantly higher in diabetic patients with renal failure (9.6%) than in diabetic patients without renal failure (3.2%) and in the general Japanese population (3.7%). This finding suggests that apo E2 is associated with renal failure in NIDDM. In addition, to elucidate the association of apo E2 with lipid abnormalities, plasma lipid and lipoprotein levels were compared among the apo E2 (E2/2 and E3/2) and E3/3 groups of NIDDM with renal failure (n = 27) and the apo E2 (E3/2) and E3/3 groups of NIDDM with normoalbuminuria (n = 34). In diabetic patients, the apo E2 group with renal failure had significantly higher levels of plasma total cholesterol (T-chol), very-low-density lipoprotein (VLDL)-chol, triglyceride (TG), VLDL-TG and apo E than the apo E3/3 group with renal failure, and had significantly higher levels of plasma T-chol, VLDL-chol, TG and VLDL-TG than the apo E2 and E3/3 groups with normoalbuminuria. Furthermore, the apo E2 group with renal failure had significantly higher ratios of VLDL-(chol/TG) and VLDL-chol/TG (an index of remnants in plasma) than the apo E3/3 group with renal failure and the apo E2 and E3/3 groups with normoalbuminuria. These results suggest that apo E2 leads to the accumulation of TG-rich lipoprotein and remnants in plasma. It is concluded that apo E2 is associated with renal insufficiency in NIDDM and that apo E2 may be a factor that aggravates lipid abnormalities in NIDDM with renal failure.

Albuminuria↗
PubMed1994

Inhibition of acto-myosin subfragment-1 ATPase activity by peptides corresponding to various segments of the 20-kDa domain of myosin heavy chain.

As reported previously, the synthetic heptapeptide having the amino acid sequence around the reactive Cys (SH1) of myosin heavy chain, IRICRKG-NH2, inhibited acto-myosin subfragment-1 (S-1) ATPase activity and half inhibition (K1/2) was observed at a peptide concentration of 0.06 mM. The inhibitory ability of the peptide was found to be decreased to one-fifth by acetylation of its N-terminal alpha-amino group. A similar effect of N-acetylation was observed with a nonapeptide, EGIRICRKG-NH2, and an undecapeptide, VLEGIRICRKG-NH2. These results indicate that N-terminal-free synthetic peptides do not act as proper analogs of the corresponding segment of S-1 heavy chain against F-actin. We isolated a longer peptide extending from Thr682 to Lys709 in S-1 heavy chain, with two Cys residues corresponding to SH1 and SH2. This peptide, having 28 residues (28peptide), inhibited acto-S-1 ATPase activity with a K1/2 of 0.23 mM. A cosedimentation binding assay indicated that the 28peptide completely dissociated acto-S-1 in the presence of ATP. This behavior is different from that observed with the N-terminal-free synthetic heptapeptide, and thus the 28peptide might be an analog of the corresponding segment. There is a possibility that the region corresponding to the 28peptide in S-1 heavy chain may bind directly with F-actin and may be involved in determining the acto-S-1 link during the steady state of the acto-S-1 ATPase reaction.

Acetylation↗