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Biomedical subjects

K Noguchi

Publications and source records attributed to K Noguchi.

At least 163 records · Page 9Linked to original sources
PubMed1998

Temperature-sensitive effects of potassium channel openers on isolated guinea pig myocardium and aorta.

The effects of K+ channel openers, NIP-121, cromakalim, and pinacidil, on isolated myocardium and aorta were investigated at two different temperatures, 23 degrees C and 37 degrees C. In right ventricular myocardium, NIP-121 shortened the action-potential duration with little influence on other action-potential parameters at 37 degrees C, but not at 23 degrees C. In whole-cell clamped ventricular myocytes, NIP-121 induced a glibenclamide-sensitive outward current at 37 degrees C but not at 23 degrees C. No difference in tissue adenosine triphosphate (ATP) concentration was detected between ventricular myocardia incubated at 37 degrees C and at 23 degrees C. In aortic preparations precontracted with norepinephrine, NIP-121, cromakalim, and pinacidil produced endothelium-independent relaxation at 37 degrees C, which was antagonized by glibenclamide. The vasorelaxant effects were greatly reduced at 23 degrees C. Thus we demonstrated that the effects of K+ channel openers on the myocardium and vascular smooth muscle are temperature sensitive.

Action Potentials↗
PubMed1998

Clinical significance of interruption of therapy with allylestrenol in patients with benign prostatic hypertrophy.

BACKGROUND: A multicenter, clinical trial investigated the effects of an interruption of antiandrogen therapy on subjective and objective clinical parameters in patients with benign prostatic hypertrophy (BPH). METHODS: Patients were given antiandrogen therapy with allylestrenol (50 mg/day) for 16 weeks. The medication was then withheld and the patients were carefully monitored for an additional 16 weeks. There were 34 BPH patients ranging in age from 55 to 82 years (mean, 66.1 years). The efficacy of allylestrenol was evaluated by its effects on prostate volume, maximum urinary flow rate (MFR), and symptom scores at the end of 16 weeks of treatment and then again at 32 weeks (16 weeks after cessation of therapy). RESULTS: Allylestrenol was effective in the treatment of BPH, and was still effective 16 weeks after the cessation of medication. The prostate volume did not change after treatment cessation nor did the total symptom score, but the MFR reversed to the pretreatment level. Serum testosterone (1.95 ng/mL), dihydrotestosterone, and gonadotropin levels decreased on therapy, but were completely reversed by the end of this study. A prostate needle biopsy revealed that after 16 weeks without therapy, some glands showed regressive glandular changes, while some glands showed slight hyperplastic changes of the secretory epithelium. Eight per cent of patients complained of loss of libido during this study. CONCLUSIONS: Allylestrenol is an effective and safe medical treatment for patients with symptomatic BPH. Hormonal and histopathologic findings suggest that the prostate gland may regrow after discontinuation of medication.

Aged↗
PubMed1998

Beneficial hemodynamic effects of nicorandil in a canine model of acute congestive heart failure: comparison with nitroglycerin and cromakalim.

Comparative hemodynamic effects of nicorandil (NCR), nitroglycerin (NTG) and cromakalim (CRM) were examined in a canine model of acute congestive heart failure (CHF). CHF was produced by injections of saponin into coronary arteries of anesthetized dogs followed by volume loading and continuous i.v. infusion of methoxamine. After the treatment, aortic blood flow (AoF), left ventricular dP/dt and myocardial segment shortening (SS) markedly decreased, while the left ventricular end-diastolic pressure (LVEDP), the right atrial pressure (RAP) and the systemic vascular resistance (SVR) increased. NCR (n = 6), NTG (n = 6) and CRM (n = 8), which were administered i.v. after production of CHF, caused a comparable reduction in LVEDP. NCR and CRM profoundly increased AoF and SS but NTG did only slightly. On the other hand, NTG and NCR but not CRM significantly reduced RAP. Intracoronary NCR (n = 8) exerted no or similar effects on SS as well as systemic hemodynamic indices to those observed with i.v. NCR despite distinct coronary vasodilation. These results indicate that NCR may exert beneficial hemodynamic effects in an experimental CHF mainly due to lessening both afterload and preload rather than the coronary vasodilating effect.

Acute Disease↗
PubMed1998

In-vitro negative chronotropic and inotropic effects of a novel dihydropyridine derivative, CD-832, in the guinea-pig: comparison with calcium-channel antagonists.

The effects of CD-832 (4R-(-)-2-(nicotinoylamino)ethyl-3-nitroxypropyl-1,4-dihydro -2,6-dimethyl-4,3-nitrophenyl, 3,5-pyridine dicarboxylate) , a novel dihydropyridine derivative, on guinea-pig isolated myocardial preparations have been compared with those of Ca2+-channel antagonists. All ten compounds induced concentration-dependent negative chronotropic effects on preparations of isolated right atria and negative inotropic effects on isolated right ventricular papillary muscles. The order of potency for the negative chronotropic effect was CD-832 > nicardipine = gallopamil > clentiazem > nifedipine = efonidipine > amlodipine = semotiadil > verapamil > diltiazem; that for the negative inotropic effect was nicardipine = gallopamil > nifedipine > verapamil > CD-832 > diltiazem > clentiazem > efonidipine = semotiadil > amlodipine. The ratio of the EC50 (the concentration of Ca2+ antagonist having 50% of the maximum effect) for the negative inotropic effect divided by the EC50 for the negative chronotropic effect, considered to be an index of selectivity for negative chronotropic effect, was higher for CD-832, amlodipine, efonidipine and semotiadil than for the other Ca2+ antagonists. The ratio for CD-832, nifedipine, nicardipine, efonidipine, amlodipine, verapamil, gallopamil, diltiazem, clentiazem and semotiadil was 11.4, 0.29, 0.87, 35.4, 37.1, 0.65, 0.87, 0.92, 7.11 and 30.0, respectively. These findings indicate that CD-832 and the newly developed Ca2+ antagonists including amlodipine, efonidipine, semotiadil and clentiazem were selective for a negative chronotropic effect rather than for a negative inotropic effect. This 'chrono-selective' effect of these drugs might be of benefit in the treatment of cardiovascular disorders.

Animals↗
PubMed1998

Acetylcholine as a signaling system to environmental stimuli in plants. III. Asymmetric solute distribution controlled by ACh in gravistimulated maize seedlings.

Asymmetric distribution of acetylcholinesterase (AChE) activity has previously been demonstrated to occur in the lower side of the gravity-stimulated maize shoot. The localization of immunoreacted IAA-inositol synthase, AChE and safranin was detected in selected organs of gravistimulated dark grown maize seedlings using a light microscope. Immunoreacted IAA-inositol synthase was asymmetrically distributed in the lower side of the stele of coleoptile node and mesocotyl in maize seedlings placed horizontally. The positive AChE spots in the coleoptile node and mesocotyl were apparently localized in the lower half of the gravistimulated seedlings. Safranin was also asymmetrically distributed in the lower half of the endodermis and stele cells of coleoptile node and mesocotyl. Namely, transport of safranin in the upper half of the coleoptile node and mesocotyl was blocked by gravistimulation. Furthermore, the asymmetric distribution of immunoreacted IAA-inositol synthase was inhibited by neostigmine bromide, AChE inhibitor. These results show that an asymmetric environmental stimulus induces changes in AChE activity, affecting IAA-inositol synthase localization and safranin transport.

Acetylcholine↗
PubMed1998

Activated mesangial cells produce vascular permeability factor in early-stage mesangial proliferative glomerulonephritis.

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a multifunctional cytokine involved in angiogenesis, inflammation, and wound healing. Although VPF/VEGF has been reported to be produced only by glomerular podocytes in glomeruli, it was found that it is produced by human cultured mesangial cells (MC). Therefore, immunohistochemical analysis (using indirect immunofluorescence and in situ hybridization) of VPF/VEGF in normal kidneys (n = 7) and biopsy specimens taken from 83 patients with renal diseases, including mesangial proliferative glomerulonephritis (PGN) (n = 58), was performed to examine whether VPF/VEGF is produced by MC in human PGN. In all of the healthy subjects and all of the patients except those with PGN (disease control subjects), VPF/VEGF protein and mRNA were detected mainly in podocytes. However, in some PGN patients, VPF/VEGF protein was demonstrated clearly in MC as well as in podocytes, as some of the VPF/VEGF was colocalized with alpha-smooth muscle actin, a marker of activated MC, and VPF/VEGF mRNA was expressed by MC and podocytes. Mesangial VPF/VEGF expression level increased significantly in PGN patients with early lesions (P < 0.01 versus healthy subjects or disease control subjects, P < 0.05 versus PGN with later lesions). The time between biopsy and disease onset was significantly shorter in PGN patients with than in those without mesangial VPF/VEGF expression (P < 0.01). These findings provide the first evidence that activated MC are a source of VPF/VEGF in human PGN, and indicate that mesangial VPF/VEGF expression is characteristic of early lesions of PGN. Because VPF/ VEGF plays a pivotal role in tissue repair, MC-produced VPF/VEGF may play pathophysiologic roles, including promoting recovery from glomerular injuries, in early-stage PGN.

Adolescent↗
PubMed1998

Dissociation between specific personal episodes and other aspects of remote memory in a patient with hippocampal amnesia.

In this paper, we describe some features of remote memory in a single-case, Y.K., with amnesic syndrome. His ability to access remote memory was investigated through a variety of tests and then analyzed in terms of specific aspects of remote memory, i.e., public events, personal semantic memory, and specific personal episodes. Although Y.K. showed relatively good performance in recalling public events, personal semantic memory, and general personal events, he was not able to recall specific personal episodes over his entire life span. That is, there appears a clear dissociation between recalling specific personal episodes and other aspects of remote memory. This suggests he lacks "richness" in his remote memory, which is probably necessary to maintain one's own identity.

Amnesia↗
PubMed1998

[Nonoperative management of major blunt renal lacerations with urinary extravasation: report of two cases].

Two cases of major blunt renal trauma with urinary extravasation managed by conservative treatment are presented herein. The first case: A 13-year-old girl fell from a bicycle. A computed tomographic (CT) scan showed right renal laceration with retroperitoneal hematoma. Renal arteriography showed evidence of fresh arterial bleeding without visualization of the lower pole. She was treated conservatively with superselective arterial embolization of the lower pole. She developed no urinoma with normal renal function. Renal renin and blood pressures stayed within the normal range in follow up studies. The second case: A 12-year-old boy fell from a tree and hit his right flank. A CT scan showed fragmentation of right renal cortex with retroperitoneal hematoma. He was treated conservatively as his vital signs remained stable, no active arterial bleeding was found no renal arteriography and both renal pelvis and ureters were well visualized by intra venous pyelography. Retroperitoneal hematoma was absorbed without formation of urinoma. Renal function remained within normal limits in follow up studies.

Adolescent↗
PubMed1998

Vasorelaxant and negative inotropic effects of gallopamil and LU49700, a metabolite of gallopamil, on isolated rat aorta and guinea-pig ventricular myocardium.

The effects of LU49700 (CAS 116759-60-5), the main metabolite of gallopamil (CAS 16662-47-8) on the mechanical response of isolated rat aortic and guinea-pig ventricular papillary muscle preparations were compared with those of gallopamil. Gallopamil and LU49700 inhibited the 64 mmol/l KCl-induced contraction of rat aorta in a concentration-dependent manner. The vasorelaxant potency of LU49700 was 244 times weaker than that of gallopamil. Gallopamil and LU49700 produced concentration-dependent negative inotropic effects on isolated right ventricular papillary muscles. The negative inotropic potency of LU49700 was 418 times weaker than that of gallopamil. These findings indicate that LU49700 has a weaker cardiovascular depressant potency than gallopamil. Therefore, LU49700 may not mediate the effects of gallopamil for treating subjects with cardiovascular diseases.

Animals↗
PubMed1998

[Long-term administration study of propiverine hydrochloride (BUP-4 tablets) in pollakiuria and urinary incontinence].

The safety and efficacy of one-year administration of propiverine hydrochloride (BUP-4 tablets) were assessed in facilities affiliated with the Department of Urology of Yokohama City University School of Medicine. Changes in subjective symptoms showed significant improvement in mean frequency of urination in the daytime from 10.3 +/- 4.0 times before administration to 7.1 +/- 2.9 times 1 year after the start of administration, in mean frequency of voiding at night from 4.2 +/- 1.7 times to 2.1 +/- 1.1 times and in mean incidence of urinary incontinence from 2.9 +/- 2.1 times to 0.7 +/- 1.0 times. The final degree of overall improvement rate was 82.0% (41/50 cases). Adverse effects were observed 26 times in 22 patients, the incidence being 15.6% (22/141 cases). They consisted of digestive symptoms in 9.9% (6 events of dry mouth, 4 of constipation, 2 of abdominal discomfort, 2 of diarrhea and 1 of gastritis), urinary tract symptoms in 3.5% (4 of dysuria and 1 of residual urine), abnormal laboratory findings in 1.4% (increase in glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase or lactate dehydrogenase levels) and others (1.4%). These results provide further evidence of the safety and efficacy of propiverine hydrochloride (BUP-4 tablets) even when administered for a long-term in the treatment of patients with pollakiuria and urinary incontinence.

Administration, Oral↗
PubMed1998

[Bilateral renal cell carcinoma in a patient with chronic renal failure: a case report].

We describe a case of bilateral renal cell carcinoma associated with chronic renal failure. A 49-year-old man was admitted to our hospital to initiate hemodialysis. He was found to have multiple renal cystic changes and a left renal mass by ultrasound. Computed tomographic (CT) scan showed a tumor 4 cm in diameter in the left kidney and another one 2 cm in diameter in the right kidney. Left nephrectomy was first performed and histopathological examination revealed renal cell carcinoma of mixed type and granular subtype. Six months after the operation, CT scan showed the mild growth of the tumor in the right kidney. Right nephrectomy was performed and histopathological examination revealed renal cell carcinoma of papillary type and granular subtype. The patient remains well on hemodialysis, with no evidence of recurrence or metastasis for 13 months after nephrectomy.

Carcinoma, Renal Cell↗
PubMed1997

Caspase-dependent apoptosis of COS-7 cells induced by Bax overexpression: differential effects of Bcl-2 and Bcl-xL on Bax-induced caspase activation and apoptosis.

Bcl-2 family proteins and ICE/CED-3 family proteases (caspases) are regarded as the basic regulators of apoptotic cell death. They are evolutionarily conserved and implicated in a variety of apoptosis. However, the precise mechanism by which these two families interact to regulate cell death is not yet known. In this study, we found that the overexpression of the Bcl-2 family member Bax induced apoptotic cell death in COS-7 cells through the activation of CPP32 (caspase-3)-like proteases that cleaved the DEVD tetrapeptide. This apoptotic cell death was suppressed by the viral proteins CrmA and p35, as well as by the chemically synthesized caspase inhibitors Z-Asp-CH2-DCB and zVAD-fmk. We also found that the Bax-induced apoptosis of COS-7 cells was suppressed by Bcl-xL and Bcl-2, though both Bcl-xL and Bcl-2 similarly prevented etoposide-induced apoptosis in COS-7 cells. In addition, Bcl-xL inhibited the activation of caspase-3-like proteases accompanying Bax-induced COS-7 cell death but Bcl-2 did not. These results indicate that the caspase activation is essential for Bax-induced apoptosis, and that the ability of Bcl-2 and Bcl-xL to prevent the Bax-induced caspase activation and apoptosis in COS-7 cells could be differentially regulated. Our results also suggest that Bcl-2 family proteins function upstream of caspase activation and control apoptosis through the regulation of caspase activity.

Animals↗
PubMed1997

Pim-1 kinase stimulates c-Myc-mediated death signaling upstream of caspase-3 (CPP32)-like protease activation.

Pim-1 oncoprotein is a serine/threonine kinase that can closely cooperate with c-Myc in lymphomagenesis, as does Bcl-2. Although the molecular mechanism of this cooperative transformation remains unknown, it is speculated that, similar to Bcl-2, Pim-1 contributes to transformation by inhibiting apoptosis. In this study, therefore, we examined the effect of Pim-1 expression on c-Myc-mediated apoptosis of Rat-1 fibroblasts triggered by serum deprivation. Our results showed that, rather than inhibiting apoptosis, Pim-1 expression stimulated c-Myc-mediated apoptosis in Rat-1 fibroblasts. Pim-1 stimulated c-Myc-mediated apoptosis through an enhancement of the c-Myc-mediated activation of caspase-3 (CPP32)-like proteases, since the suppression of this activity by a specific caspase inhibitor abolished the apoptosis stimulation by Pim-1. A kinase-defective Pim-1 mutant failed to stimulate c-Myc-mediated apoptosis, and Pim-1 expression alone in the absence of c-Myc overexpression did not induce apoptosis of serum-deprived Rat-1 cells, indicating that the kinase activity of Pim-1 and the activated c-Myc signaling pathway were required for apoptosis stimulation by Pim-1. Together, these results suggest that Pim-1 oncoprotein stimulates as a serine/threonine kinase the death signaling elicited by c-Myc at a step upstream of caspase-3-like protease activation in Rat-1 fibroblasts. Our results also suggest that Pim-1 kinase might function cooperatively with c-Myc through the phosphorylation of a factor(s) which regulates the common signaling pathway involved in c-Myc-mediated apoptosis and transformation.

Animals↗
PubMed1997

Cloning of cDNA and expression of the gene encoding rat presenilin-2.

We have cloned the rat homologue of the presenilin-2 (PS-2) cDNA. PS-2 is responsible for chromosome 1-linked familial Alzheimer's disease. Sequence analysis predicted that the rat PS-2 encodes a 448 amino acid (aa) protein, and there was a very high degree of amino acid identity between rat and human PS-2 (95%). All the mutated codons in PS-2 and PS-1 in chromosome 1- or 14-linked familial Alzheimer's disease patients were conserved in rat PS-2. The expression of PS-2 was weaker than that of PS-1. The alternatively spliced short form of PS-2 mRNA, which was detected in human tissues was not detected in various rat tissues. During brain development, the expression level of both PS-2 and PS-1 increased but decreased in the adult. No remarkable change was observed in neural differentiation of PC12 cells.

Alternative Splicing↗
PubMed1997

Expression of beta-calcitonin gene-related peptide in axotomized rubrospinal neurons and the effect of brain derived neurotrophic factor.

The mRNA levels for alpha- and beta-calcitonin gene-related peptide (CGRP) in rat rubrospinal neurons were studied by in situ hybridization 3, 7, 14, 28 and 56 days following cervical spinal hemisection. CGRP-like immunoreactivity (LI) in the rubrospinal neurons and the rubrospinal tract in cervical spinal cords were examined using immunohistochemistry. There was almost no signal for alpha- and beta-CGRP mRNAs and undetectable level of CGRP-LI in the rubrospinal neurons ipsilateral to cervical spinal hemisection (control side). Fourteen days after spinal hemisection, the rubrospinal neurons contralateral to cervical hemisection (axotomized side) showed CGRP-LI in their cell bodies, and CGRP containing fibers were observed in the lateral funiculi just proximal, but not distal, to the injury sites. In situ hybridization showed upregulation of beta-CGRP mRNA in a subpopulation of the rubrospinal neurons on the axotomized side. The proportion of beta-CGRP mRNA-expressing neurons reached its maximum (approximately 19%) 4 days following axotomy and slowly decreased to about 5% 56 days after axotomy. The percentage of alpha-CGRP mRNA-expressing neurons was much lower than that of beta-CGRP mRNA (maximum about 2.6% 4 days after axotomy) and not significantly different from the control side throughout the time period studied. These data indicate that axotomy induces de novo synthesis of the CGRP beta-subtype in rubrospinal neurons and that the beta-CGRP is transported to the injury site through the rubrospinal tract. In addition, we studied the effect of the intracerebral injections of brain derived neurotrophic factor (BDNF). BDNF treatment fully reversed the severe cell atrophy that followed axotomy and increased the number of neurons labeled for beta-CGRP mRNA, but did not increase the percentage of rubrospinal neurons expressing beta-CGRP mRNA. Thus, topical application of BDNF does not have direct modulatory effect on CGRP induction in axotomized neurons in the red nucleus.

Animals↗