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Biomedical subjects

J Hama

Publications and source records attributed to J Hama.

17 recordsLinked to original sources
PubMed2001

Is Chordin a morphogen?

Models employing gradients of diffusible morphogens are often invoked to explain regional specification in the early embryo. In these models, a concentration gradient of a secreted factor generates distinct cell fates, based on the differential response of cells to local concentrations of this morphogen. In recent years, there has been a great deal of focus on the factors involved in the dorsoventral patterning of the vertebrate mesoderm and ectoderm. Dorsoventral specification during amphibian gastrulation is regulated by the antagonistic actions of the Bone Morphogenetic Proteins (BMPs) and a number of dorsally expressed inhibitors, including the secreted factor, Chordin. In a recent paper, Blitz and colleagues explore the possibility that Chordin acts as a long-range factor in the amphibian gastrula embryo, to establish a functional gradient of BMP activity.

Animals↗
PubMed2001

SNT-1/FRS2alpha physically interacts with Laloo and mediates mesoderm induction by fibroblast growth factor.

Members of the fibroblast growth factor (FGF) ligand family play a critical role in mesoderm formation in the frog Xenopus laevis. While many components of the signaling cascade triggered by FGF receptor activation have been identified, links between these intracellular factors and the receptor itself have been difficult to establish. We report here the characterization of Xenopus SNT-1 (FRS2alpha), a scaffolding protein previously identified as a mediator of FGF activity in other biological contexts. SNT-1 is widely expressed during early Xenopus development, consistent with a role for this protein in mesoderm formation. Ectopic SNT-1 induces mesoderm in Xenopus ectodermal explants, synergizes with low levels of FGF, and is blocked by inhibition of Ras activity, suggesting that SNT-1 functions to transmit signals from the FGF receptor during mesoderm formation. Furthermore, dominant-inhibitory SNT-1 mutants inhibit mesoderm induction by FGF, suggesting that SNT-1 is required for this process. Expression of dominant-negative SNT-1 in intact embryos blocks mesoderm formation and dramatically disrupts trunk and tail development, indicating a requirement for SNT-1, or a related factor inhibited by the mutant construct, during axis formation in vivo. Finally, we demonstrate that SNT-1 physically associates with the Src-like kinase Laloo, and that SNT-1 activity is required for mesoderm induction by Laloo, suggesting that SNT-1 and Laloo function as components of a signaling complex during mesoderm formation in the vertebrate.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Alpha1-adrenergic stimulation induced hypertrophy in protein kinase C down-regulated cultured cardiac myocytes.

To examine whether protein kinase C (PKC) activation is essential for the induction of cardiac myocyte hypertrophy caused by alpha1-adrenergic stimulation, we investigated the hypertrophic effect of phenylephrine in PKC down-regulated and non-treated cultured cardiac myocytes obtained from neonatal Sprague-Dawley rat ventricles. The treatment with 10 nmol/L 12-tetra decanoylphorbol-13-acetate (TPA) for more than 2 hours decreased PKC activity by approximately 80% without marked hypertrophy. Phenylephrine increased [14C] phenylalanine (Phe) incorporation in both TPA non-treated and treated cells, 1.54- and 1.71-fold as large as control, respectively. The cell surface area also enlarged in both groups, 1.67- and 1.74-fold, respectively. Thus, phenylephrine induced the similar grade hypertrophy in cultured cardiac myocytes even when PKC was down-regulated. These results suggest that conventional PKC activation may not be essential for mediating myocyte hypertrophy by alpha1-adrenergic stimulation.

Adrenergic alpha-Agonists↗
PubMed1997

Short-acting nifedipine and diltiazem do not reduce the incidence of cardiac events in patients with healed myocardial infarction. Secondary Prevention Group.

BACKGROUND: The administration of calcium antagonists to patients with healed myocardial infarction is a controversial treatment. This study was conducted to elucidate the effect of short-acting nifedipine and diltiazem on cardiac events in patients with healed myocardial infarction. METHODS AND RESULTS: A controlled clinical open trial of 1115 patients with healed myocardial infarction was carried out between 1986 and 1994. The patients included 595 who received no calcium antagonist, 341 who received short-acting nifedipine 30 mg/d, and 179 who received short-acting diltiazem 90 mg/d. The primary end points were cardiac events, which were defined as fatal or nonfatal recurrent myocardial infarction; death from congestive heart failure; sudden death; and hospitalization because of worsening angina, congestive heart failure, or premature ventricular contractions. Cardiac events occurred in 51 patients (8.6%) in the no-calcium-antagonist group and 54 (10.4%) in the calcium-antagonist group (odds ratio, 1.24; 95% CI, 0.83 to 1.85), demonstrating that the calcium antagonists did not reduce the incidence of cardiac events. Subgroup analysis revealed no beneficial effects of these drugs for reducing cardiac events in patients with such complications as hypertension or angina pectoris. CONCLUSIONS: This study showed that use of short-acting nifedipine and diltiazem in this postmyocardial infarction population was associated with a 24% higher cardiac event rate, but this strong adverse trend did not reach statistical significance.

Aged↗
PubMed1997

Aspirin plus either dipyridamole or ticlopidine is effective in preventing recurrent myocardial infarction. Secondary Prevention Group.

The efficacy of combining antiplatelet agents with low doses of aspirin to prevent cardiac events in patients with myocardial infarction was examined. A total of 1,083 patients with prior myocardial infarction were randomly divided into those who were (618) and were not (465) treated with antiplatelet agents, and observed for 12.5 +/- 18.5 months. Those treated with antiplatelet agents included 113 patients treated with aspirin (50 mg) plus dipyridamole (150 mg/day), 253 treated with aspirin (50 mg) plus ticlopidine (200 mg/day), and 252 treated with only 1 of the 3 antiplatelet agents. Cardiac events, including fatal or nonfatal recurrent myocardial infarction, death by congestive heart failure, and sudden death, occurred in 34 patients (7.3%) in the nontreatment group and in 19 patients (3.1%; p < 0.01) in the treatment group; odds ratio 0.40, 95% confidence interval 0.23-0.71. There were only 2 cardiac events (1.8%) in the aspirin + dipyridamole group (p < 0.05 vs nontreatment group: odds ratio 0.28: 0.08-1.03), and 5 such events (2.0%) in the aspirin + ticlopidine group (p < 0.01; odds ratio 0.28: 0.11-0.69). Subgroup analysis to exclude differences in the patients' background confirmed the efficacy of these antiplatelet agents. We conclude that combined treatment with low doses of aspirin plus either dipyridamole or ticlopidine is effective in preventing cardiac events in patients who have had prior myocardial infarction.

Aged↗
PubMed1997

[Prevention of cardiac events by beta-blocking agents in elderly patients after myocardial infarction].

We retrospectively analyzed the effect of beta-blocking agents on the incidence of cardiac events in elderly patients who had had myocardial infarction. A total of 1169 patients who had had a myocardial infarction (age, 60.2 +/- 11.4 years) were followed for a mean of 18.0 +/- 19.7 months and the incidence of cardiac events (fatal or nonfatal myocardial infarction, sudden cardiac death, and death due to congestive heart failure) was computed. There were 21 cardiac events in 653 patients who received beta-blocking agents (3.2%) and 39 events in 516 patients who did not receive beta-blocking agents (7.6%, p < 0.01). Among patients less than 50 years old, the incidences of cardiac events were 4.1% in those who received beta-blocking agents and 7.6% in those who did not; among those 50 to 59 years old the incidences were 3.0% and 7.5%, respectively; among those 60 to 69 years old they were 4.3% and 6.0%, respectively; and among those 70 years old or older they were 0.8% and 11.4%, respectively (p < 0.01). We found that beta-blocking agents prevented cardiac events both in elderly and in younger patients after myocardial infarction.

Adrenergic beta-Antagonists↗
PubMed1996

Long-term nitrate treatment increases cardiac events in patients with healed myocardial infarction. Secondary Prevention Group.

BACKGROUND: Nitrates dilate coronary arteries, ameliorate myocardial ischemia, minimize left ventricular remodeling, and reduce mortality in patients with acute myocardial infarction. However, the effects of long-term treatment with nitrates on cardiac events in patients with healed myocardial infarction are not known. METHODS AND RESULTS: A total of 1,002 patients with healed myocardial infarction (789 male and 213 female) were randomly divided into 2 groups: treatment with nitrates or nontreatment. The mean observation period was 18.0 +/- 19.9 months. Primary end points were nonfatal and fatal recurrent myocardial infarction, death from congestive heart failure, and sudden death. Baseline characteristics of the 2 groups were also compared to determine any effects on outcome. Among the 621 cases treated with nitrates, 41 cases (6.6%) experienced cardiac events during the observation period, whereas only 12 of the 381 cases that were not treated with nitrates (3.1%) had cardiac events. This difference was statistically significant (p < 0.05; odds ratio 2.17; 95% confidence interval 1.13-4.19). There were no differences in the incidence of noncardiac death or being lost to follow-up between the 2 groups. Although the precise mechanism of this increase in the occurrence of cardiac events by long-term treatment with nitrates is not clear, nitrate tolerance with possible rebound and neurohormonal effects may be involved. CONCLUSION: Long-term treatment with nitrates increased cardiac events in patients with healed myocardial infarction.

Aged↗
PubMed1995

Effect of an angiotensin II receptor antagonist, TCV-116, on neointimal formation following balloon injury in the SHR carotid artery.

1. In the present study, we examined the effect of a novel angiotensin II type I receptor antagonist, TCV-116, on carotid neointimal formation after balloon injury in SHR and WKY rats. 2. Oral administration of TCV-116 at a dose of 10 mg/kg per day reduced not only systolic blood pressure but also neointimal formation after carotid balloon injury. TCV-116 also suppressed cardiac hypertrophy. An angiotensin-converting enzyme inhibitor, lisinopril (20 mg/kg per day), had a similar effect to that of TCV-116. 3. In the WKY experiment, both TCV-116 and lisinopril suppressed neointimal formation as well as systolic blood pressure, but did not suppress cardiac hypertrophy. 4. Although SHR showed markedly enhanced neointimal formation after balloon injury compared with age-matched WKY rat, both TCV-116 and lisinopril showed similar suppressive effects on neointimal formation in both SHR and WKY rats. 5. These results confirm the important role of angiotensin II in neointimal formation following balloon injury. Further studies are needed to clarify the mechanism of the difference between SHR and WKY rats in the response of vascular smooth muscle cells.

Angiotensin II↗
PubMed1995

Atrial natriuretic peptide and antihypertensive action due to beta-blockade in essential hypertensive patients.

The effects of beta-blocker treatment on hemodynamics were studied in relation to plasma atrial natriuretic peptide (ANP) levels in 17 outpatients with essential hypertension. Administration of propranolol for twelve weeks to untreated subjects resulted in a significant (P < 0.001) rise in plasma ANP levels (from 37.9 +/- 21.2 to 66.7 +/- 46.2 pg/mL, mean +/- SD). Systolic and diastolic blood pressures were significantly decreased (P < 0.05 and P < 0.01, respectively). Heart rate was also significantly decreased (P < 0.001). On the other hand, a significant reduction of cardiac index was detected (from 4.12 +/- 1.34 to 2.96 +/- 0.75 L/min/m2, P < 0.01) with chronic administration of propranolol, suggesting a reflection of decreased cardiac function. A significant negative correlation was observed between %changes in systolic blood pressure and %changes in plasma ANP (r = -0.594, P < 0.05). These results suggest that the increased plasma ANP levels may contribute to the antihypertensive effect with propranolol.

Adrenergic beta-Antagonists↗
PubMed1994

Effect of an angiotensin II receptor antagonist, TCV-116, on rat carotid artery neointimal formation after balloon injury.

Arterial injury by a balloon catheter produces marked smooth muscle cell proliferation and the participation of angiotensin II in this response has been suggested. In this study, we examined the effect of a novel angiotensin II type I receptor antagonist, TCV-116, on neointimal formation after rat carotid artery balloon injury. Oral administration of TCV-116 at doses of 1, 5 or 10 mg/kg/day significantly reduced the cross-sectional intimal area by 30%, 46% and 54%, respectively, and reduced the ratio of the intimal to medial cross-sectional areas by 23%, 41% and 50%. An angiotensin-converting enzyme inhibitor, lisinopril, had an effect similar to that of TCV-116. The effect of both drugs was significantly correlated with the reduction of both blood pressure and cardiac hypertrophy. We conclude that TCV-116 can prevent neointimal formation after balloon injury as well as reducing blood pressure and preventing cardiac hypertrophy.

Angiotensin Receptor Antagonists↗
PubMed1993

Characterization of renal aldosterone receptors in genetically hypertensive rats.

To investigate the aldosterone responsiveness of genetically hypertensive rats, we compared characteristics of renal cytosolic aldosterone receptors from the M strain of stroke-prone, spontaneously hypertensive rats (M-SHRSP) with normotensive Wistar-Kyoto rats (WKY). In M-SHRSP, blood pressure was elevated significantly at 6 wk of age, when their plasma aldosterone concentrations were similar to those in WKY. Decreases in urine volume and sodium excretion were also observed in M-SHRSP. At 10 wk of age, M-SHRSP plasma aldosterone concentrations became significantly higher than those in WKY. On the other hand, the concentration of renal cytosolic aldosterone receptors (type I, aldosterone specific) had already increased at 6 wk of age in M-SHRSP, with no difference in affinity, and levels remained increased thereafter. There were no significant differences in molecular weights or ionic charges of either "activated" or "non-activated" aldosterone-receptor complexes between M-SHRSP and WKY, indicating that the molecular properties were similar in both groups. These results suggest that the increased concentration of aldosterone receptors in the kidneys of M-SHRSP might increase their aldosterone responsiveness and contribute to the development of high blood pressure in these animals.

Animals↗
PubMed1989

Regulation of aldosterone receptor in rat kidney cytosol by atrial natriuretic factor.

We investigated the effect of atrial natriuretic factor (ANF) on aldosterone receptors in the kidney cytosol, because the binding of aldosterone to aldosterone receptors in the cytosol is considered a critical step of its action. Rat atriopeptin III was injected into male Sprague-Dawley rats (200-250 g) via the femoral vein while under pentobarbital anesthesia, and aldosterone receptors in the kidney cytosol were determined. The maximum binding capacity and dissociation constant were calculated by the Scatchard analysis. Maximum binding capacity of both types of aldosterone receptor (Type I, high affinity and low binding capacity and Type II, low affinity and high binding capacity) gradually decreased after ANF injection, reached the lowest level after 2 hours, and then slightly recovered. When more than 2.5 micrograms/kg of rat atriopeptin III was injected, the density of aldosterone receptors significantly decreased. Injection of 12.5 micrograms/kg of rat atriopeptin III decreased maximum binding capacity of Type I receptor from 42.3 +/- 2.4 (mean +/- SD, n = 6) to 22.8 +/- 3.2 femtomole/mg protein (n = 6) (p less than 0.01), and that of Type II receptor decreased from 388 +/- 46 to 285 +/- 30 fmol/mg protein (p less than 0.01). Dissociation constant of both types of receptors did not change significantly after ANF injection. Plasma aldosterone concentration showed no significant change after ANF injection, and a significant change was noted after ANF administration on aldosterone receptors in the experiments on adrenalectomized rats 7 days after operation. Furosemide had no significant effect on aldosterone receptors in both normal and adrenalectomized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMedDate not supplied

Effects of dilevalol and propranolol on hemodynamics in patients with essential hypertension.

Eighteen patients with essential hypertension received 50 to 200 mg of dilevalol or 60 to 90 mg of propranolol daily for six weeks. Mean arterial blood pressure and venous pressure were significantly reduced in the dilevalol-treated patients at six weeks but were unchanged in the propranolol-treated patients. The cardiac index and systemic vascular resistance remained unchanged in the dilevalol group, but were significantly reduced (cardiac index) or increased (systemic vascular resistance) in the propranolol group. No changes in heart rate were noted in either treatment group. It is concluded that dilevalol has some ideal features for the treatment of hypertension, but further research is needed to determine the causes of fatal hepatotoxicity reported in a few cases.

Blood Pressure↗