Biomedical subjects

M Kohno

Publications and source records attributed to M Kohno.

At least 199 records · Page 11Linked to original sources

PubMed1997

Vascular dopamine-I receptors and atherosclerosis.

Vascular smooth muscle cell (VSMC) migration and proliferation are believed to play key roles in atherosclerosis. To elucidate the role of vascular dopamine D1-like receptors in atherosclerosis, the effects of dopamine, specific D1-like agonists SKF 38,393, and YM 435 on platelet-derived growth factor (PDGF) BB-mediated VSMC migration, proliferation, and hypertrophy were studied. We observed that cells stimulated by 5 ng/ml PDGF BB showed increased migration, proliferation and hypertrophy. These effects were prevented by coincubation with dopamine, SKF 38,393, or YM 435 at 1-10 mumol/l, and this prevention was reversed by Sch 23,390 (1-10 mumol/l), a specific D1-like antagonist. These actions are mimicked by 1-10 mumol/l forskolin, a direct activator of adenylate cyclase and 8-bromocyclic AMP at 0.1-1 mmol/l. The actions are blocked by a specific protein kinase A (PKA) inhibitor N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinoline-sulfonamide (H 89), but are not blocked by its negative control, N-[2-(N-formyl-p-chlorocinnamylamino) ethyl]-5-isoquinoline sulfonamide (H 85). PDGF-BB (5 ng/ml)-mediated activation of phospholipase D (PLD), protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) activity were significantly suppressed by coincubation with dopamine. These results suggest that vascular D1-like receptor agonists inhibit migration, proliferation and hypertrophy of VSMC, possibly through PKA activation and suppression of activated PLD, PKC and MAPK activity.

Animals↗

PubMed1997

Sympathetic nerve response to microgravity induced by parabolic flight.

The aim of this study was to clarify how muscle sympathetic nerve activity (MSNA) in humans, which plays an important role in blood pressure control against gravity, is altered under microgravity conditions. Subjects were seated in a jet aircraft with their legs extended. MSNA was recorded microneurographically from the tibial nerve of the sitting subjects with simultaneous monitoring of electrocardiogram, blood pressure, respiration, and intrathoracic blood volume during parabolic flights. In the Air Force training area, the aircraft made parabolas up to 10 times. At the entry to microgravity, intrathoracic blood volume increased, systemic blood pressure was elevated, and MSNA was suppressed. However, this MSNA suppression lasted only 10-15 sec, and then followed by an enhancement to the end of the parabolas. We conclude that MSNA is suppressed at the onset of microgravity during parabolic flight in response to loading of the cardiopulmonary volume receptor due to a cephalad body fluid shift. However, this MSNA suppression is transient during such dynamic gravitational changes as those induced by parabolic flight, probably modulated by arterial baroreceptors.

Adult↗

PubMed1997

Changes in plasma cardiac natriuretic peptides concentrations during 1 year treatment with angiotensin-converting enzyme inhibitor in elderly hypertensive patients with left ventricular hypertrophy.

Plasma concentrations of atrial and brain natriuretic peptides (ANP and BNP) are high in patients with hypertension and congestive heart failure. The present study examined changes in plasma ANP and BNP concentrations during 1 year of monotherapy with enalapril in elderly hypertensive patients with left ventricular (LV) hypertrophy. Eight elderly hypertensive patients with LV hypertrophy were treated with enalapril for 1 year, during which time serial changes were recorded in LV mass index, LV systolic function, and plasma concentrations of ANP and BNP. Enalapril maintained systolic and diastolic blood pressure in the normal range for over 1 year. Treatment significantly reduced posterior wall thickness at 6 months, and more so at 1 year, and tended to reduce septal wall thickness and LV mass index at 1 year. LV ejection fraction was slightly but significantly increased at 1 year. Plasma ANP and BNP, which were markedly elevated at study entry, both decreased after 1 year of enalapril. These results suggest that 1 year of treatment with enalapril caused both a modest regression of LV hypertrophy and a modest improvement in LV systolic function in our selected group of elderly hypertensive patients. The drug reduced elevated plasma ANP and BNP levels but did not alter BUN and serum creatinine levels. Enalapril appears to be useful for the treatment of elderly hypertensive patients with LV hypertrophy.

Aged↗

PubMed1997

[Outcome from surgery of lung cancer invading the carina].

By 1995, 17 patients with lung cancer invading the carina underwent surgical resection and reconstruction of the carina. Procedures which applied to patients were two cases of wedge pneumonectomy, seven cases of sleeve pneumonectomy, four cases of carinal reconstruction with right upper lobectomy, and four cases of carinal resection and reconstruction. Overall survival for five years were 40.3% and 33.6% for ten years survival. Operative death occurred in 5 cases. Long term survival was achieved in localized diseases which showed no lymph node extension. As for N1 and N2 diseases, only one patient among 7 cases survives 12 months. Thus we conclude that selected cases which showed localized disease without lymph node extension are the candidate for carinal resection and reconstruction. Postoperative intensive care is mandated for these patients. Adjuvant therapy with surgery for these patients with lymph node progression is a future problem.

Adult↗

PubMed1997

[Application of NGF/PC12 cell system for screening tubulin inhibitors].

Microtubules are stiff polymers that extend throughout the cytoplasm of eukaryotic cells and regulate the location of intracellular compartments. Microtubules are formed by the polymerization of tubulin molecules, each of which is a heterodimer consisting of two closely related globular polypeptides, alpha-tubulin and beta tubulin. Many of the microtubule arrays are labile and are turning over rapidly; they depolymerize and repolimerize continually in living cells. One of the most striking examples is the mitotic spindle, which forms after the cytoplasmic microtubules disassemble at the onset of mitosis. The mitotic spindle is the target of a variety of agents that act by interfering with the exchange of tubulin subunits between the microtubules and the free tubulin pool; some of these agents can be used as antimitotic or anticancer drugs. We recently have developed a simple and sensitive method of screening for tubulin inhibitors, to which we have successfully applied the nerve growth factor/PC12 cell system. In this report, we describe the details of this method for screening tubulin inhibitors, by which we have analyzed several well-known and new compounds a model experiments.

Animals↗

PubMed1997

[Clinical analysis of adjuvant chemotherapy using 5-fluorouracil, leucovorin and cis-diamminedichloroplatinum for patients with advanced and recurrent gastric cancer].

The chemotherapy combining 5-FU, CDDP, and LV was conducted in 17 patients with advanced and recurrent gastric cancer. The regimen consisted of 5-FU (by continual infusion 600 mg/m2/day for 5 days), CDDP (low-dose consecutive drip infusion, 2 hours 20 mg/m2/day for 3 days) and LV (by bolus infusion 20 mg/ m2/day for 5 days). Advanced gastric cancer was found in 12 cases (operation performed in 9 cases and 7 cases resectable) and recurrent in 5 cases. Macroscopic judgment of efficacy in 10 recurrent and inoperable cases revealed CR in 1 patient, PR in 5 patients, NL in 2, and PD in 2 patients. The overall response rate was 60.0%. There were 7 resectable cases, 4 PR patients, 1 MR and 2 NC patients. The overall response rate was 57.1%. Operations were done in 9 of 12 patients with advanced gastric cancer. The histological effects in 7 cases with resectable cases were as follows: 1 patient of grade 0, 2 patients of grade 1a, 3 patients of grade 1b, and 1 patient of grade 2. The main adverse reactions were gastrointestinal symptoms, but in 3 cases thrombocytopenia was found. This chemotherapy for advanced and recurrent gastric cancer shows excellent clinical efficacy.

Adenocarcinoma↗

PubMed1997

[Constrictive pericarditis complicated with hepatic coma--a case report].

A 39-year-old man with pedal edema and icterus was admitted to our hospital. Laboratory findings revealed hyperbilirubinemia. Echocardiography and chest CT revealed the calcified mass front of the right ventricle. As cardiac catheterization showed dip and plateau in right ventricle, the diagnosis of constrictive pericarditis was established. Considering his condition and bleeding tendency with hepatic failure, plasma exchange was done for three days before operation. As the patient's condition deteriorated with hepatic coma, pericardiectomy was performed. The median sternotomy approach without cardiopulmonary bypass was selected. The calcified mass was removed, and the thickened pericardium was excised. Postoperative hemodynamic findings were improved, and the serum bilirubin returned to normal. In conclusion even in this case with severe hepatic failure due to constrictive pericarditis, surgical treatment should have be considered.

Adult↗

PubMed1997

[Surgical outcomes of transverse aortic arch replacement].

The surgical outcomes of transverse aortic arch replacement were analyzed for the cases of 33 consecutive patients who underwent operations during the seven years between July 1989 and March 1996. Sixteen patients were atherosclerotic aneurysm (group T), 17 patients were acute or chronic aortic dissection involving aortic arch (group D). As for brain protection during aortic arch reconstruction, selective cerebral perfusion was employed in 16 patients of group T and 11 patients of group D. In 6 patients of group D with acute type A aortic dissection or chronic type B dissection, deep hypothermic circulatory arrest at 18 approximately 20 degrees C of rectal temperature was employed. In 14 patients of group T, selective cerebral perfusion was simultaneously started when we begun cardiopulmonary bypass. There were one operative death in group T patients (operative mortality 6.2%) and two in group D patients (operative mortality 11.8%). Perioperative stroke was occurred in two patients of group T with complete recovery in one and with partial recovery in the other. The latter patient died of medistinitis and graft infection. There was no hospital death nor stroke in group D patients. Duration of selective cerebral perfusion was 157.8 +/- 54.4 minutes in group T patients, 140.1 +/- 66.5 minutes in group D patients (n = 11), duration of circulatory arrest was 49.5 +/- 11.4 minutes in 6 patients of group D patients, respectively. In 27 patients who underwent operation with selective cerebral perfusion, morbidity of stroke was 7.4% (two patients). These were caused by technical failure during arch vessel reconstruction and seemed to be avoidable. In conclusion, it is reasonable to employ selective cerebral perfusion for aortic arch reconstruction in atherosclerotic aneurysm of transverse aortic arch. In aortic dissection, either selective cerebral perfusion or deep hypothermic circulatory arrest is justified as cerebral protection during operation.

Adult↗

PubMed1997

[A study on antiprothrombin antibodies in antiphospholipid syndrome].

In this study we investigated the frequency and the type of manifestations of antiprothrombin antibodies (aFII) in patients with antiphospholipid syndrome (APS). In 16 (84.2%) of 19 patients with lupus anticoagulant (LA) and either anticardiolipin antibodies or antiphosphatidylserine antibodies, two types of abnormal patterns were shown on a crossed immuno-electrophoresis technique using anti-human prothrombin murine IgG. The slow-moving peak of prothrombin was detected in 8 patients, while a peak in the other patients had the slow-moving shoulder. These slow-moving materials might represent prothrombin-aFII complexes. In 13 patients who were studied on Western blots, IgGs of 11 patients (84. 6%) bound to human purified prothrombin, and the IgGs of 7 (53.8%) of these patients also bound to human purified alpha-thrombin. Our results indicate that aFII detected in patients with APS may explain part of the mechanism of LA.

Adolescent↗

PubMed1997

Effect of oxidized low density lipoprotein on thrombomodulin expression by THP-1 cells.

We have investigated the effects of oxidized low density lipoproteins (oxidized LDL) on the expression of TM by THP-1 monocytic cells. TM antigen levels and its cofactor activity for thrombin-dependent protein C activation were increased by oxidized LDL and accompanied by an increase in TM mRNA levels. Incubation of THP-1 cells with 300 microg/ml oxidized LDL for 24 h resulted in an 80% increase of cellular TM antigen levels. Native LDL and acetylated LDL did not affect the TM expression by these cells. The resultant aqueous phase after extraction of oxidized LDL by chloroform/methanol increased the TM antigen levels as well as oxidized LDL. Phorbol 12-myristate 13-acetate (PMA) also increased the TM antigen level 2.1 times the control and was accompanied by the adhesion of cells to plastic dishes and increasing macrophage cell surface antigen CD14 levels. In contrast, oxidized LDL did not induce differentiation to the macrophage. The present results indicate that oxidized LDL increases cellular TM antigen without cellular differentiation and that up-regulation of TM by oxidized LDL in monocytes may have some implication in atherosclerosis.

Arteriosclerosis↗

PubMed1996

Influence of aortic impedance on the development of pressure-overload left ventricular hypertrophy in rats.

BACKGROUND: Aortic input impedance, which represents LV afterload, is considered to be a major determinant for the development of pressure-overload left ventricular (LV) hypertrophy. METHODS AND RESULTS: To test whether the sustained change in aortic input impedance might affect the mode of development of LV hypertrophy, coarctation of either the ascending aorta (G1, n = 13) or suprarenal abdominal aorta (G2, n = 12) was performed over 4 weeks in 6-weeks-old Wistar rats. Although peak LV pressure and total systemic resistance were increased similarly in G1 and G2, time to peak LV pressure was decreased by 24% (P < .01) in G1 compared with G2. The aortic input impedance spectra revealed that the early systolic loading in G1 was characterized by an increase in characteristic impedance, whereas the late systolic loading in G2 was by an augmented arterial wave reflection. G1 showed a smaller increase (P < .01) in either the ratio of LV weight (mg) to body weight (g) or LV wall thickness than G2 after aortic banding. Myocyte diameter was also smaller (P < .05) in G1 (14.3 +/- 0.7 mm) than in G2 (16.1 +/- 1.2 mm). The ex vivo passive pressure-volume relation had a rightward shift in G1 compared with G2, suggesting less concentric LV hypertrophy in G1. CONCLUSIONS: The sustained early systolic loading due to the increase in characteristic impedance was accompanied by less concentric, reduced hypertrophy, whereas the sustained late systolic loading due to the augmented arterial wave reflection was accompanied by concentric, adequate hypertrophy.

Aldosterone↗

PubMed1996

Characterization of the bone morphogenetic protein-2 as a neurotrophic factor. Induction of neuronal differentiation of PC12 cells in the absence of mitogen-activated protein kinase activation.

Rat pheochromocytoma PC12 cells are shown to express a single class of high affinity binding sites for bone morphogenetic protein (BMP)-2 (1,300 receptors/cell, Kd = 31.3 pM). Affinity cross-linking using radiolabeled BMP-2 demonstrated the presence of six components with apparent molecular masses of 170, 155, 105, 90, 80, and 70 kDa. BMP-2 induced morphological changes in PC12 cells with the concomitant expression of three neurofilament proteins. Thus, BMP-2 would appear to be another neurotrophic factor that, like nerve growth factor or basic fibroblast growth factor, stimulates the neuronal differentiation of PC12 cells. Unlike nerve growth factor and basic fibroblast growth factor, however, BMP-2 failed to induce the activation of either 41- and 43-kDa mitogen-activated protein (MAP) kinases or the MAP kinase/extracellular signal-regulated kinase kinase (MEK). Also, BMP-2 did not induce the expression of the c-fos gene in PC12 cells. Activin A was also capable of inducing the neuronal differentiation of PC12 cells without activating MAP kinases and MEK. These findings show a clear dissociation between the requirement for the activation of the MAP kinase cascade and the ability of BMP-2 and activin A to induce PC12 cell neuronal differentiation. In addition, these results suggest that the activation of MAP kinases and MEK is not an absolute requirement for PC12 cell differentiation.

Adrenal Gland Neoplasms↗

PubMed1996

Simultaneous measurement of Ca2+ and pH by laser cytometry using fluo-3 and SNARF-1.

We present a new convenient method for simultaneous measurement of intracellular calcium concentration ([Ca2+]i) and intracellular pH (pHi) using laser cytometry with a mixture of fluo-3 (for [Ca2+]i) and SNARF-1 (for pHi), with iso excitation (488 nm)-dual emission (530 nm for fluo-3 and > 630 nm for SNARF-1). By using this technique, we measured the changes in [Ca2+]i and pHi in A-431 human epidermoid carcinoma cells and HSG human salivary gland cells stimulated by ATP. We found that alkalization in A-431 cell occurred with the elevation of [Ca2+]i; in contrast, alkalization in HSG cells did not occur at all, even though the elevation of [Ca2+]i was observed. Using BAPTA (a chelating agent of Ca2+) and amiloride (an inhibitor of the Na+/H+ exchanger), we found that the elevation of pHi requires the elevation of [Ca2+]i but that the elevation of [Ca2+]i does not always require a rise in pHi. From our results we conclude that elevation of [Ca2+]i takes precedence over the elevation of pHi in ATP-stimulated signal transduction.

Adenosine Triphosphate↗

PubMed1996

Very low density lipoprotein receptor binds apolipoprotein E2/2 as well as apolipoprotein E3/3.

The VLDL receptor, a newly identified lipoprotein receptor, recognizes apoE containing lipoproteins. The human VLDL receptor was overexpressed in 1d1A-7, a mutant Chinese hamster ovary cells lacking LDL receptors. Each VLDL obtained from a normolipidemic subject with two epsilon3 or epsilon2 alleles similarly competed for the binding of radiolabeled rabbit beta-VLDL to the VLDL receptors. The anti-apoE monoclonal antibody 1D7, which inhibited binding of apoE3 to the LDL receptors, failed to compete for the binding of VLDL (apoE3 or apoE2) to the VLDL receptors. Results indicate that the binding site of apoE on the VLDL receptor may differ from its binding site on the LDL receptor.

Animals↗

PubMed1996

Dissociation of c-fos induction and mitogen-activated-protein kinase activation from the hepatocyte-growth-factor-induced motility response in human gastric carcinoma cells.

The function of hepatocyte growth factor/scatter factor (HGF/SF) is to increase proliferation as well as to stimulate motility and disperse cell colonies of epithelial cells. In this study, we examined the motogenic and mitogenic responses of two human gastric carcinoma cell types, MKN7 and MKN74. Cell motility of both cell lines was markedly stimulated by HGF/SF. In contrast, HGF/SF stimulated cell growth of MKN74 cells, but did not stimulate growth of MKN7 cells. To address the cause of the difference in response of these cells, which may reflect some differences in signaling pathways downstream from the HGF/SF receptor, c-Met, we investigated the induction of the proto-oncogene c-fos. The level of c-fos mRNA increased and reached a maximum approximately 40 min after HGF/SF stimulation in MKN74 cells, and thereafter its level rapidly decreased. In contrast, the level of c-fos expression was very low irrespective of the stimulation in MKN7 cells. c-Fos protein was transiently induced only in MKN74 cells l h after treatment with HGF/SF, and its levels subsequently decreased. We subsequently examined the activation of mitogen-activated-protein kinase, which is a major mediator in the signaling pathway leading to the stimulation of c-fos transcription, after HGF/SF treatment in both cell lines. Mitogen-activated-protein kinase was markedly activated by this treatment in MKN74 cells, but was only slightly activated in MKN7 cells. These results suggest that although mitogen-activated-protein kinase activation and c-fos induction play an essential role in the signaling pathway leading to cell growth, they are not required for the motility response induced by HGF/SF.

Adenocarcinoma↗

PubMed1996

Tumor necrosis factor (TNF) stimulates the production of nerve growth factor in fibroblasts via the 55-kDa type 1 TNF receptor.

The role of the two types of tumor necrosis factor (TNF) receptors, TNF-R1 and TNF-R2, in mediating the capacity of TNF to stimulate nerve growth factor (NGF) production in fibroblasts has been investigated. Although Swiss 3T3 cells express both the TNF-R1 and TNF-R2, an agonistic anti-TNF R1 antibody, but not an agonistic anti-TNF-R2 antibody, increases the NGF mRNA level and stimulates the production of NGF protein in the cells. Treatment of the cells with a combination of anti-TNF-R2 antibody and interleukin-1 beta (IL-1 beta) does not increase the NGF production induced by IL-1 beta alone, although TNF's activity to stimulate NGF production is markedly enhanced by IL-1 beta. Furthermore, simultaneous addition of the both antibodies does not increase the NGF production above that observed with the anti-TNF-R1 antibody, indicating that TNF-R1 alone mediates the TNF's activity to stimulate NGF production in fibroblasts.

3T3 Cells↗

PubMed1996

Solitary metastasis to the choroid plexus of the lateral ventricle. Report of three cases and a review of the literature.

Three cases of cancer metastasis to the choroid plexus of the lateral ventricle are reported. The metastases were from sigmoid colon cancer, renal cell carcinoma and pulmonary cancer, and were located in the trigone in two cases and the right inferior horn in one. Total removal was accomplished in all cases without any complications. In addition, eight reported cases of single brain metastasis to the choroid plexus of the lateral ventricle, including clinical and radiological features, are discussed. Peritumoral edema on computed tomographic (CT) scan or magnetic resonance (MR) imagining was found to be an important feature of metastasis developing at this site.

Aged↗

PubMed1996

An accelerated increase of plasma adrenomedullin in acute asthma.

A novel vasorelaxant peptide, adrenomedullin (AM), has been isolated from the acid extract of human pheochromocytoma. We have recently shown that AM inhibits histamine- and acetylcholine-induced bronchoconstriction in anesthetized guinea pigs in vivo, and this bronchodilatory effect is long-lasting. Here, we measured plasma AM concentrations in nine patients with an acute attack of bronchial asthma. The results were compared with values in 30 age-matched normal control subjects and seven age-matched stable asthmatic patients. The mean AM concentrations of patients with an acute asthma attack (98 +/- 22 pg/mL) were clearly higher than those of normal control subjects (18 +/- 2 pg/mL) and stable asthmatic patients (21 +/- 3 pg/mL). Reverse-phase high-performance liquid chromatography (HPLC) showed that the major component of plasma immunoreactive AM in patients with an asthma attack and in normal subjects equally corresponded to authentic human AM(1-52). Our results suggest that plasma AM is markedly increased in many of the patients during an acute attack of bronchial asthma, but it is not observed in stable asthmatic patients. Although this report is preliminary, the observed increase of circulating AM during an acute asthma attack may represent a compensatory mechanism against the bronchoconstriction, probably through its bronchodilatory action.

Acute Disease↗