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Biomedical subjects

M Kohno

Publications and source records attributed to M Kohno.

At least 235 records · Page 13Linked to original sources
PubMed1996

[Cardiac contractile dysfunction in response to surgical stress including trauma, hemorrhage, and infection].

Shock and multiple organ failure are complications of primary conditions such as trauma, hemorrhage and infection. Ample evidence of cardiac contractile dysfunction has been obtained in both septic patients and experimental animal models of endotoxin shock. Recent advance in molecular biology and immunology has improved our understanding of the pathogenesis of septic shock, and thus, it is now believed that the host's inflammatory response to infection contributes to the development of septic shock. In addition, effects of toxic host mediators including cytokines, kinins, eicosanoids, platelet-activating factor, and nitric oxide, which are produced by activated cells, on cardiovascular system have been examined. The possible involvement of the nitric oxide pathway, not only as a marker for cytokine-induced effects on myocyte gene expression, but also as a mediator for cytokine-induced contractile dysfunction, was explored. According to this hypothesis, trauma and hemorrhage, both of which lead to host's inflammatory response, is also considered to induce contractile dysfunction. In this paper we reviewed the influences of various shock states on cardiac contractility. Hemorrhagic and burn shocks possibly depress cardiac contractility as well as septic and endotoxin shocks. Therefore, it is necessary to improve contractile depression in the diseased states to meet oxygen demand of each patient under monitoring patient's circulatory and metabolic conditions.

Animals↗
PubMed1996

[Aortic valve injury due to blunt trauma--treatment in acute phase].

Aortic valve injury due to blunt trauma is rare and often difficult to diagnose. Therefore, most reported cases are operated on months or years after initial injury. Reported below is the case of a 55-year-old male, who was involved in a head-on collision with a bus. He was transported to Tsukuba Medical Center by ambulance, 34 minutes after the accident. The patient presented acute shock without obvious evidence of hemorrhaging. On physical examination a murmur was detected. The murmur was evaluated by Doppler echocardiography and revealed aortic regurgitation. On further physical examination he had gross hematuria and intratracheal bleeding. Computerized tomography (CT) showed evidence of contusions to his lungs, liver, and kidneys. The individual was diagnosed with an aortic valve injury, causing aortic insufficiency. It was necessary to continuously monitor the patients' hemodynamic state, assessing when conditions to operate were most favorable. However, in the hyper-acute phase the bleeding is difficult to control. We waited for his platelet count to recover before operating on the fifth day. When the patient underwent valve repair using extracorporeal circulation (ECC), aprotinin was added to the procedure. The surgery revealed a large laceration on the right coronary cusp of the aortic valve. Repair to the valve was impossible, so replacement of the aortic valve was required. A Carbomedics mechanical valve (phi 21 mm) was inserted. The patient did well after surgery, and eventually returned to work. To date, in Japan, there are eleven such cases of aortic valve injury on file. However, this is the first reported case that involved operating during the acute phase. This case demonstrates that, with careful evaluation of coexisting injuries and control of bleeding, successful treatment of aortic valve injury using ECC is possible, even in the acute phase.

Aortic Valve↗
PubMed1995

Cell type-specific modulation of cell growth by transforming growth factor beta 1 does not correlate with mitogen-activated protein kinase activation.

Transforming growth factor beta 1 (TGF-beta 1) is a multifunctional cytokine that positively or negatively regulates the proliferation of various types of cells. In this study we have examined whether or not the activation of the mitogen-activated protein (MAP) kinases is involved in the transduction of cell growth modulation signals of TGF-beta 1, as MAP kinase activity is known to be closely associated with cell cycle progression. Although TGF-beta 1 stimulated the growth of quiescent Balb 3T3 and Swiss 3T3 cells, it failed to detectably stimulate the tyrosine phosphorylation and activation of the 41- and 43-kDa MAP kinases at any time point up to the reinitiation of DNA replication. TGF-beta 1 also failed to stimulate the expression of the c-fos gene. Furthermore, TGF-beta 1 synergistically enhanced the mitogenic action of epidermal growth factor (EGF) without affecting EGF-induced MAP kinase activation in these fibroblasts, and it inhibited the EGF-stimulated proliferation of mouse keratinocytes (PAM212) without inhibiting EGF-induced MAP kinase activation. Thus, the ability of TGF-beta 1 to modulate cell proliferation is apparently not associated with the activation of MAP kinases. In this respect, TGF-beta 1 is clearly distinct from the majority, if not all, of peptide growth factors, such as platelet-derived growth factor and EGF, whose ability to modulate cell proliferation is closely associated with the activation of MAP kinases. These results also suggest that the activation of MAP kinases is not an absolute requirement for growth factor-stimulated mitogenesis.

3T3 Cells↗
PubMed1995

Constitutive activation of mitogen-activated protein (MAP) kinases in human renal cell carcinoma.

Mitogen-activated protein kinases (MAPKs) play a pivotal role in the mitogenic signal transduction pathway and are essential components of the MAPK cascade, which includes MEK (also known as MAP kinase kinase), Raf-1, and Ras. In this study, we examined whether constitutive activation of the MAPK cascade was associated with the carcinogenesis of human renal cell carcinomas in a series of 25 tumors and in corresponding normal kidneys. Constitutive activation of MAPKs in tumor tissue, as determined by the appearance of phosphorylated forms, was found in 12 cases (48%), and this activation was confirmed by a direct in vitro kinase assay of immunoprecipitate using myelin basic protein as the substrate. The phosphorylation of MEK and of Raf-1, as monitored by a mobility shift in SDS-PAGE, which is reportedly associated with the activation of these kinases, occurred in 9 of 18 cases (50%) and in 6 of 11 cases (55%) respectively. The activation of MAPKs was correlated with MEK activation (P = 0.0045) and with Raf-1 activation (P = 0.067). Furthermore, overexpression of MEK was found in 13 of 25 cases (52%) by Western blot analysis, and this overexpression was associated significantly with MAPK activation (P = 0.034). No mutations were noted in H-,K-, or N-ras genes by PCR direct sequencing in any of the 25 tumor samples. Of the patients studied, 8 of 18 (44%) stage pT2 patients and four of six (67%) stage pT3 patients showed MAPK activation. The single stage pT1 patient did not evidence MAPK activation. Furthermore, one of seven (14%) grade 1 patients, 9 of 13 (69%) grade 2 patients, and two of five (40%) grade 3 patients showed MAPK activation (grade 1 versus grades 2 and 3, P = 0.046). Our results suggest that constitutive activation of MAPKs may be associated with the carcinogenesis of human RCCs.

Amino Acid Sequence↗
PubMed1995

A note on population dynamics.

Population dynamics is analyzed by means of the power series expansion of a decay ratio F(P) with respect to the continuation probability, P, of survival. The truncation of the higher terms of the series yields the Verhulst equation as a first approximation. The approximation for higher age yields a simple exponential decay law of population, while the younger-age approximation recovers Gompertz's empirical law of human mortality. It is shown that there exists a finite survival probability in the limit of t = infinity. The validity of the present result is examined with real population dynamics of centenarians. In order to construct a commensurable definition of aging, an aging phenomenon in decay process is considered on the assumption of an ideal society, from which a simple relationship is derived between the extent of advancement of aging and the continuation probability.

Aging↗
PubMed1995

The activation and nuclear translocation of extracellular signal-regulated kinases (ERK-1 and -2) appear not to be required for elongation of neurites in PC12D cells.

The outgrowth of neurites was induced in PC12D cells, a subline of PC12 cells, that were treated not only with NGF but also with dbcAMP, staurosporine or bFGF. Simultaneous activation and rapid nuclear translocation of MAP kinases (ERK-1 and ERK-2) were observed in cells treated with NGF or bFGF. But staurosporine and dbcAMP induced no or only slight activation of the kinases. The nuclear translocation of the MAP kinases was not induced by the latter agents. These observations suggest a close relationship between the activation and the nuclear translocation of MAP kinases and, moreover, that stimulation and relocalization of MAP kinases might not be required for the outgrowth of neurites from PC12D cells. Staurosporine and dbcAMP may stimulate a down-stream step of the NGF pathway, or a parallel pathway(s) to the MAP kinase cascade in promoting neurite formation from PC12D cells. These agents mimic the effects of NGF in promoting neurite outgrowth in cultured sympathetic neurons, but not in conventional PC12 cells. Because of the similarity between PC12D cells and primed cells, it seems possible that activation and nuclear translocation of MAP kinases might be required for the transcription-dependent differentiation step but might not be necessary for the elongation of neurites at least in response to staurosporine or to dbcAMP.

Alkaloids↗
PubMed1995

Increased nitric oxide production in patients with hypotension during hemodialysis.

OBJECTIVE: To determine the involvement of nitric oxide production in hemodialysis-induced hypotension. DESIGN: Examination of nitric oxide synthesis, cyclic guanosine 3'5'-monophosphate (cGMP) levels, and endothelin-1 levels in plasma before and after hemodialysis. SETTING: Veterans Affairs medical center. PATIENTS: 13 patients with end-stage renal failure who were receiving hemodialysis: Six patients had hypotensive episodes during dialysis and 7 did not. INTERVENTION: Patients received heparin at a bolus dose of 2000 U at the initiation of dialysis followed by 1000 U/h during 4-hour hemodialysis sessions. RESULTS: Nitric oxide production markedly increased during hemodialysis-induced hypotensive episodes; this increase was not seen in patients who did not have a hypotensive episode. In both groups, the plasma cGMP and endothelin-1 levels decreased after hemodialysis. According to multiple regression analysis, standard coefficients of nitric oxide production, plasma cGMP levels, and endothelin-1 levels with mean blood pressure after hemodialysis were -0.743, -0.07, and 0.31, respectively. CONCLUSION: Nitric oxide production increased in patients who had a hypotensive episode during hemodialysis but did not increase in those who did not have a hypotensive episode.

Aged↗
PubMed1995

Enhancement of the binding of triglyceride-rich lipoproteins to the very low density lipoprotein receptor by apolipoprotein E and lipoprotein lipase.

The low-density lipoprotein (LDL) receptor plays a crucial role in cholesterol metabolism. A related protein, designated the very low density lipoprotein (VLDL) receptor, that specifically binds apolipoprotein (apo) E has recently been characterized and shown to be expressed in heart, muscle and adipose tissue and the human monocyte-macrophage cell line THP-1. The VLDL receptor binds and internalizes VLDL and intermediate density lipoprotein from Watanabe heritable hyperlipidemic (WHHL) rabbits as well as beta-migrating VLDL from cholesterol-fed rabbits but not LDL from WHHL rabbits. Chinese hamster ovary (CHO) cells transfected with the rabbit VLDL receptor cDNA have now been shown to bind or internalize VLDL (d < 1.006 g/ml) isolated from fasted normolipidemic human subjects with lower affinity than WHHL-VLDL or rabbit beta-VLDL. However, binding and internalization were markedly enhanced when fasted human VLDL was preincubated with either recombinant human apoE (3/3) or lipoprotein lipase (LPL) in CHO cells overexpressing the rabbit or human VLDL receptor. CHO cells transfected with both the rabbit VLDL receptor cDNA and the human LPL cDNA effectively bound, internalized, and degraded fasted human VLDL without pretreatment. Treatment of heparinase reduced the effect of LPL-mediated binding at 4 degrees C, but the inhibitory effect was lower at 37 degrees C. Pseudomonas LPL also enhanced the binding of human fasted VLDL to the VLDL receptor at 37 degrees C in CHO cells overexpressing the human VLDL receptor. Taken together, LPL causes the enhancement of triglyceride-rich lipoproteins binding to the VLDL receptor via both the formation of bridge between lipoproteins and heparan sulfate proteoglycans and its lipolytic effect. Ligand blot analysis showed that the apparent molecular mass of the VLDL receptor is 118 kDa, which is smaller than that of the LDL receptor. These results indicate that the VLDL receptor recognizes both triglyceride-rich lipoproteins that are also relatively rich in apoE, as well as the remnants of triglyceride-rich lipoproteins after catabolism and the interaction with heparan sulfate proteoglycans by LPL. The VLDL receptor may thus function as a receptor for remnants of triglyceride-rich lipoproteins in extrahepatic tissues.

Apolipoproteins E↗
PubMed1995

Distribution and characterization of specific cellular binding proteins for bone morphogenetic protein-2.

Bone morphogenetic proteins (BMPs), which were originally identified by their novel ability to induce de novo cartilage and bone formation in vivo, are multifunctional proteins structurally related to transforming growth facto-beta s, activins, and inhibins. As a first step to elucidate the precise physiological function as well as the action mechanism of BMPs, we have examined the distribution of the specific cellular binding proteins for BMP-2 on a wide variety of cell types. A single class of high affinity-specific binding sites for BMP-2 were identified not only on osteoblastic cells but also on major types of non-hematopoietic cells in a rather ubiquitous fashion (1,200-60,000 receptors/cell, Kd = 35-230 pM); these cells included fibroblasts, keratinocytes, astrocytes, kidney epithelial cells, and tumor cells of bone, muscle, lung, liver, kidney, stomach, colon, prostate, and neuronal tissue. Other growth factors including transforming growth factor-beta 1, activin A, and inhibin A did not compete for the binding of 125I-labeled BMP-2 to the cells. Affinity cross-linking of radiolabeled BMP showed five components with apparent molecular masses of 170, 105, 90, 80, and 70 kDa common to all three fibroblast cell lines analyzed. On the other hand, no specific binding sites for BMP-2 were identified on vascular endothelial cells or on hematopoietic cells including RPMI 1788 and RPMI 8226 (B-lymphocyte lineage), MOLT-3 and MOLT-4 (T-lymphocyte lineage), HL-60 (myeloid lineage), and K-562 (erythroid lineage). These results suggest that major types of cells other than hematopoietic cells and vascular endothelial cells may be potential targets for BMP-2 action.

Animals↗
PubMed1995

Lipid accumulation and foam cell formation in Chinese hamster ovary cells overexpressing very low density lipoprotein receptor.

The rabbit very low density lipoprotein receptor gene was introduced into LDL receptor-negative Chinese hamster ovary cells (ldl-A7). Incubation of the transfected cells with rabbit beta-VLDL (5 to 8 micrograms protein/ml), for 6 days, induced foam cell formation. The cells accumulated lipid droplets visualized by oil red-O staining; the cellular cholesteryl ester and triglyceride content increased two- to threefold. [3H]Oleate incorporation into cholesteryl [3H]oleate was stimulated threefold by incubation of cells with beta-VLDL (20 micrograms protein/ml). Northern blot analysis revealed the presence of VLDL receptor mRNA in rabbit resident alveolar macrophages. Incubation of the macrophages with beta-VLDL (20 micrograms protein/ml) for 24 hours induced foam cell formation but had virtually no effect on VLDL receptor mRNA abundance. These results suggest that the VLDL receptor on macrophages may play an important role in foam cell formation.

Animals↗
PubMed1995

Regional diastolic function in effort angina pectoris: assessment with biplane left ventriculography.

To investigate left ventricular (LV) regional diastolic function in effort angina pectoris (AP), we performed left ventriculography in 14 patients with AP and isolated left anterior descending artery disease and in 9 normal subjects (N). LV volume (V), regional area (S) [anterior, apex, and inferior], and the first derivative of V and S (dV/dt, dS/dt) were derived from analysis of the left ventriculogram. Normalized peak filling rate (nPFR) and peak atrial filling rate (nPAFR) were derived from dV/dt. The ratio of filling volume to stroke volume during rapid filling and atrial contraction were defined as rapid filling fraction (RFF) and atrial filling fraction (AFF). Similarly, peak area changing rate (PACR), peak area changing rate during atrial contraction (PACRac), rapid area changing fraction (RACF), and atrial area changing fraction (AACF) were derived from S and dS/dt. We also calculated the time constant of LV relaxation (T), and LV global and regional compliance during atrial contraction [(dV/VdP)ac, (dS/SdP)ac]. The LV global diastolic function (T increases, nPFR decreases) was impaired in the angina patients. LV regional diastolic function (nPACR decreases, RACF decreases) was also impaired in the affected region of the AP group. While their rapid filling was impaired, nPACRac was maintained and AACF was increased in the affected region. Furthermore, nPACR and RACF each showed a significant inverse correlation with AACF in the anterior region [r = -0.57 (P < 0.01), r = -0.92 (P < 0.001)]. In the affected region of the patients with AP, (dS/SdP)ac was increased, but not significantly. Thus, LV global and regional diastolic functions were simultaneously impaired in patients with isolated left anterior descending artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Hepatocellular carcinoma complicating biliary cirrhosis caused by biliary atresia: report of a case.

A case of hepatocellular carcinoma complicating biliary cirrhosis caused by biliary atresia is reported. The patient had persistent severe jaundice with hepatosplenomegaly. A liver tumor was suspected because of the elevated serum alpha-fetoprotein and was shown by ultrasonography at 6 years of age. The tumor was treated with percutaneous ethanol injection therapy (PEIT). Nine months after initiation of PEIT, the patient died of massive bleeding from a metastatic tumor.

Biliary Atresia↗
PubMed1995

Cardiac natriuretic peptides inhibit cyclosporine-induced production of endothelin in cultured rat mesangial cells.

Cyclosporine A (CSA) stimulates vascular endothelial cell production of endothelin-1 (ET-1). The present study was designed to test two hypotheses: (1) CSA stimulates ET-1 secretion in cultured rat mesangial cells, and (2) cardiac natriuretic peptides, atrial and brain natriuretic peptides (ANP and BNP), inhibit the above-mentioned secretion in these cells. CSA stimulated ET-1 secretion in a concentration-dependent manner between 10 and 100 ng/mL. In contrast, high concentrations of CSA (10 and 100 micrograms/mL) were cytotoxic and failed to stimulate ET-1 secretion. Rat ANP (1-28) and rat BNP-45 exhibited clearly concentration-related inhibition of CSA-induced ET-1 secretion. This inhibition by ANP and BNP was paralleed by an increase in the cellular level of cyclic guanosine-3',5'-monophosphate (cGMP). Rat ANP (5-25) was less effective than rat ANP (1-28) with respect to inhibiting ET-1 secretion and increasing cellular cGMP. Addition of a cGMP analog, 8-bromo-cGMP, reduced CSA-induced ET-1 secretion. On the other hand, addition of a cyclic adenosine-3',5'-monophosphate (cAMP) analog, 8-bromo-cAMP, did not affect CSA-induced ET-1 secretion. These findings suggest that CSA in low concentrations stimulates ET-1 production in cultured rat mesangial cells, and that cardiac natriuretic peptides inhibit this stimulated production, probably through a cGMP-dependent process.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Stimulation of cyclic adenosine monophosphate formation by the novel vasorelaxant peptide adrenomedullin in cultured rat mesangial cells.

The present study was designed to examine the effect of synthetic adrenomedullin (AM), a novel vasorelaxant peptide originally isolated from human pheochromocytoma, on intracellular cyclic adenosine monophosphate (cAMP) formation in cultured rat mesangial cells. The effect of AM on cAMP formation in rat mesangial cells was compared with its effect in cultured rat vascular smooth muscle cells. cAMP levels were determined by radioimmunoassay after stimulation for 30 minutes with different concentrations (10(-10) to 10(-7) mol/L) of rat and human AM. Rat and human AM concentration-dependently (10(-9) to 10(-7) mol/L) stimulated cAMP formation in cultured mesangial cells. This stimulatory effect of rat AM was significantly greater than human AM. The stimulatory effect of rat AM in mesangial cells was significantly weaker than its potency in vascular smooth muscle cells. These preliminary data suggest that mesangial cells, as well as vascular smooth muscle cells, possess AM receptors functionally coupled to adenylate cyclase.

Adrenomedullin↗
PubMed1995

Functional prognosis after treatment of spinal radiculomeningeal arteriovenous malformations.

BACKGROUND: We performed surgical treatment successfully in six patients with spinal radiculomeningeal arteriovenous malformation (AVM); however, only four patients showed improvement of gait function postoperatively. METHODS: These experiences prompted us to review the clinical findings and their possible association with the functional outcome in 33 reported cases of radiculomeningeal AVM together with those in our six patients. RESULTS: Statistical analysis revealed that the duration from onset of symptoms until diagnosis, the age at the time of treatment, the condition of the deep tendon reflexes (DTR) in the lower extremities, as well as the severity of both gait and urinary disturbance before treatment were significantly correlated with the functional outcome. CONCLUSIONS: A patient under 70 years old, who is treated within 2 years 6 months after the onset, whose gait or urinary disturbance is slight or moderate, and without absence of DTR in the lower extremities, is expected to have a good functional prognosis after treatment.

Aged↗
PubMed1995

Surgical treatment of stage I and II oral squamous cell carcinomas: analysis of causes of failure.

Sixty-one patients with stage I and II squamous cell carcinomas of the oral cavity treated by surgery alone were analysed to investigate treatment outcome, pattern of failure, and occurrence of second malignant neoplasms. The disease recurred or developed lately in 11 patients. The ipsilateral neck was the most common site of failure. Salvage treatment was successful in only three of these patients. Occult neck metastasis was found in 31% of patients with T2 tumours. Second malignant neoplasms developed in 20 patients and were the cause of death in 8 patients. In conclusion, locoregional control of stage I and II oral carcinomas is achieved by surgery alone. Elective neck dissection is required for patients with stage II tumours, showing a high risk of lymph node metastasis in histology.

Actuarial Analysis↗
PubMed1995

ESR demonstration of nitric oxide production from nitroglycerin and sodium nitrite in the blood of rats.

Electron spin resonance (ESR) spectra of iron-metal complexes formed by the reaction between nitric oxide (NO) and hemoglobin (Hb), referred to as nitrosylhemoglobin (HB-NO), were observed in rat blood treated in vitro and in vivo with nitroglycerin (GTN) at 77K. The same types of spectra were also detected in rats treated with sodium nitrite (NaNO2). Two types of Hb-NO, which were identified by ESR parameters of g values and superhyperfine coupling constants (shfcc), were the 6- and 5-coordinated complexes. These two types of Hb-NO were generated in a dose-dependent manner in the blood after intraperitoneal administration of 1.5-6 mg of GTN. At the higher dose of GTN (6 mg), the 6-coordinated complex was the major species generated initially, but within 10 min, the 5-coordinated complex increased time-dependently. Quantitative analysis of Hb-NO revealed that when GTN 0.3 mg and 0.6 mg was administered sublingually in rats, the concentration of Hb-NO observed in rat blood was 30% higher than the estimated concentration of GTN. The methemoglobin and peroxide complex of hemoglobin were observed in the blood incubated with GTN at 37 degrees C. These results suggest that the function of GTN was related to oxidative stress with the generation of Hb-NO. Therefore, monitoring of Hb-NO levels may be useful as an indicator of the function of various vasodilators.

Animals↗